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Yale BIDS Xu Lab 38

JAMA_FINAL203

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old man presented with gradual onset of blurry vision in both eyes for several months. Best-corrected visual acuity was 20/20 OD and 20/40 OS. Intraocular pressure was 23 mm Hg in both eyes and was more than 21 mm Hg in both eyes on multiple visits. Medical history included hypertension, obesity, left adrenalectomy, and pterygium excision surgery in the left eye. The patient denied previous episodes of blurry vision, history of corticosteroid use, sleep apnea, or type-A personality. Complete review of systems was otherwise negative. Amsler grid testing revealed paracentral metamorphopsia in both eyes. Extraocular motility, pupillary light reactions, and confrontational visual fields were normal. Slitlamp examination and gonioscopy results were normal in both eyes. An external photograph of the patient is shown in Figure 1A. Fluorescein angiography demonstrated multiple areas of late pinpoint leakage and patches of mottled hyperfluorescence in both eyes (Figure 1B). ### OUTPUT:

Bilateral central serous chorioretinopathy secondary to pituitary microadenoma

['Neurology', 'Neurosurgery', 'Ophthalmology', 'Diabetes and Endocrinology', 'Endocrinology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old woman presented with gradual onset of blurry vision in both eyes for several months. Best-corrected visual acuity was 20/20 OD and 20/40 OS. Intraocular pressure was 23 mm Hg in both eyes and was more than 21 mm Hg in both eyes on multiple visits. Medical history included hypertension, obesity, left adrenalectomy, and pterygium excision surgery in the left eye. The patient denied previous episodes of blurry vision, history of corticosteroid use, sleep apnea, or type-A personality. Complete review of systems was otherwise negative. Amsler grid testing revealed paracentral metamorphopsia in both eyes. Extraocular motility, pupillary light reactions, and confrontational visual fields were normal. Slitlamp examination and gonioscopy results were normal in both eyes. An external photograph of the patient is shown in Figure 1A. Fluorescein angiography demonstrated multiple areas of late pinpoint leakage and patches of mottled hyperfluorescence in both eyes (Figure 1B). ### OUTPUT:

JAMA_FINAL204

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 19-year-old man presented with 4 years of facial numbness and 3 years of progressive dysarthria and dysphagia. Additionally, 18 months prior to presentation, he also developed arm weakness and hand atrophy followed by leg weakness 1 year later. On examination, dysarthria, bilateral peripheral facial paralysis (Figure, A), reduced facial touch and vibration sensitivity in the mandible, temporal muscle atrophy (Figure, B), and poor soft palate motility were observed. Corneal reflexes were bilaterally absent. Deltoid, calf, and distal muscle atrophy (Figure, C) and weakness (right extensor carpi, Medical Research Council [MRC] grade 0; neck flexion, MRC grade 4; proximal muscles, MRC grade 3; other arm distal muscles, MRC grade 2-3; leg distal muscles, MRC grades 2-4) were observed. Absence of the bilateral biceps and triceps reflexes, right patellar tendon hyperreflexia, discontinuous clonus in the left knee, a Babinski sign present on the right side, and an unstable and steppage gait were also observed. ### OUTPUT:

Facial onset sensory and motor neuronopathy

['Neurology', 'Swallowing and Dysphagia', 'Facial Nerve']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 19-year-old woman presented with 4 years of facial numbness and 3 years of progressive dysarthria and dysphagia. Additionally, 18 months prior to presentation, she also developed arm weakness and hand atrophy followed by leg weakness 1 year later. On examination, dysarthria, bilateral peripheral facial paralysis (Figure, A), reduced facial touch and vibration sensitivity in the mandible, temporal muscle atrophy (Figure, B), and poor soft palate motility were observed. Corneal reflexes were bilaterally absent. Deltoid, calf, and distal muscle atrophy (Figure, C) and weakness (right extensor carpi, Medical Research Council [MRC] grade 0; neck flexion, MRC grade 4; proximal muscles, MRC grade 3; other arm distal muscles, MRC grade 2-3; leg distal muscles, MRC grades 2-4) were observed. Absence of the bilateral biceps and triceps reflexes, right patellar tendon hyperreflexia, discontinuous clonus in the left knee, a Babinski sign present on the right side, and an unstable and steppage gait were also observed. ### OUTPUT:

JAMA_FINAL205

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 50s with hypertension who was otherwise in good health presented for new ophthalmologic evaluation in the setting of mild, long-standing blurred vision with slight metamorphopsia in the right eye. She had a history of high myopia (approximately 9 diopters [D] OD; 8 D OS). Examination revealed an otherwise normal left eye with 20/20 best-corrected visual acuity (BCVA). The right eye demonstrated a BCVA of 20/25 and normal anterior segment, including lenticular examination. Dilated fundus examination showed wrinkling of the neurosensory retina at the fovea (Figure 1A) without posterior vitreous detachment. Spectral-domain optical coherence tomography revealed hyperreflective layering on the foveal surface consistent with epiretinal membrane, as well as splitting of the outer plexiform layer with hyporeflective cavities (Figure 1B). ### OUTPUT:

Foveal retinoschisis with epiretinal membrane in the setting of pathologic myopia

['Ophthalmology', 'Macular Diseases', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Foveal retinoschisis with epiretinal membrane in the setting of pathologic myopia. Case report: A man in his 50s with hypertension who was otherwise in good health presented for new ophthalmologic evaluation in the setting of mild, long-standing blurred vision with slight metamorphopsia in the right eye. He had a history of high myopia (approximately 9 diopters [D] OD; 8 D OS). Examination revealed an otherwise normal left eye with 20/20 best-corrected visual acuity (BCVA). The right eye demonstrated a BCVA of 20/25 and normal anterior segment, including lenticular examination. Dilated fundus examination showed wrinkling of the neurosensory retina at the fovea (Figure 1A) without posterior vitreous detachment. Spectral-domain optical coherence tomography revealed hyperreflective layering on the foveal surface consistent with epiretinal membrane, as well as splitting of the outer plexiform layer with hyporeflective cavities (Figure 1B). ### OUTPUT:

JAMA_FINAL206

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old man with Duchenne muscular dystrophy (DMD) presented with a recent bilateral and painless decrease of best-corrected visual acuity to light perception OD and counting fingers OS. Results of a slitlamp examination showed iris neovascularization and posterior subcapsular cataract in the right eye and no anterior segment abnormalities, including no iris neovascularization, in the left eye. Intraocular pressure was 60 mm Hg in the right eye and 14 mm Hg in the left eye. The fundus in the right eye (Figure, A) showed a total retinal detachment with hemorrhagic prepapillary fibrosis reaching up to the posterior capsule; the left eye (Figure, B) showed peripapillary tractional retinal detachment with proliferative vitreoretinopathy, retinal neovascularization, and vitreous hemorrhage. Fluorescein angiography showed extensive retinal capillary and arteriolar nonperfusion and peripapillary neovascularization in both eyes. ### OUTPUT:

Duchenne muscular dystrophy–associated proliferative retinal vasculopathy

['Ophthalmology', 'Muscular Dystrophy', 'Neurology', 'Neuromuscular Diseases', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old woman with Duchenne muscular dystrophy (DMD) presented with a recent bilateral and painless decrease of best-corrected visual acuity to light perception OD and counting fingers OS. Results of a slitlamp examination showed iris neovascularization and posterior subcapsular cataract in the right eye and no anterior segment abnormalities, including no iris neovascularization, in the left eye. Intraocular pressure was 60 mm Hg in the right eye and 14 mm Hg in the left eye. The fundus in the right eye (Figure, A) showed a total retinal detachment with hemorrhagic prepapillary fibrosis reaching up to the posterior capsule; the left eye (Figure, B) showed peripapillary tractional retinal detachment with proliferative vitreoretinopathy, retinal neovascularization, and vitreous hemorrhage. Fluorescein angiography showed extensive retinal capillary and arteriolar nonperfusion and peripapillary neovascularization in both eyes. ### OUTPUT:

JAMA_FINAL207

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 50s presented with painful palmar and plantar purpura that lasted for 2 months (Figure, A). The lesions first appeared on the volar aspect of the left hand and resolved spontaneously within a few days. However, the purpura soon relapsed on the left plantar area. Oral administration of aspirin and limaprost alfadex was ineffective, and the purpura spread on the palms and feet, followed by onset of left hemiplegia with dysarthria. The patient had no history of arterial or coronary catheterization, hyperlipidemia, hepatitis, nor endocrine neoplasia. The patient’s body temperature and laboratory test results, including inflammatory markers, were slightly elevated. Autoimmune blood tests, including antinuclear antibody, anticardiolipin antibody, and lupus anticoagulant, were not detected. Lentiginosis was not evident. A skin biopsy of the purpura of the left plantar area was conducted (Figure, B). ### OUTPUT:

Cutaneous embolization of cardiac myxoma

['Cardiology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 50s presented with painful palmar and plantar purpura that lasted for 2 months (Figure, A). The lesions first appeared on the volar aspect of the left hand and resolved spontaneously within a few days. However, the purpura soon relapsed on the left plantar area. Oral administration of aspirin and limaprost alfadex was ineffective, and the purpura spread on the palms and feet, followed by onset of left hemiplegia with dysarthria. The patient had no history of arterial or coronary catheterization, hyperlipidemia, hepatitis, nor endocrine neoplasia. The patient’s body temperature and laboratory test results, including inflammatory markers, were slightly elevated. Autoimmune blood tests, including antinuclear antibody, anticardiolipin antibody, and lupus anticoagulant, were not detected. Lentiginosis was not evident. A skin biopsy of the purpura of the left plantar area was conducted (Figure, B). ### OUTPUT:

JAMA_FINAL208

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy woman in her early 70s was referred to our emergency department with exertional dyspnea. She reported recent physical and emotional stress from work and dizziness 2 days prior to presentation. She denied fever or palpitations. Her blood pressure was 84/59 mm Hg. A harmonic, musical systolic murmur was heard at the left third intercostal space. An electrocardiogram (ECG; Figure 1A) showed diffuse ST-segment elevation, most prominently in the anterior precordial leads. Laboratory evaluation revealed elevated levels of troponin (1.33 ng/mL; normal range: ≤0.016 ng/mL [to convert to micrograms per liter, multiply by 1.0]), brain natriuretic peptide (376.5 pg/mL; normal range: ≤18.4 pg/mL [to convert to nanograms per liter, multiply by 1.0]), creatinine phosphokinase (96 U/L; normal range: 41-153 U/L), and D-dimer (0.68 μg/mL; normal range: ≤1.00 μg/mL [to convert to nanomoles per liter, multiply by 5.476]). Echocardiography showed left ventricular (LV) wall-motion abnormalities involving the mid and apical segments and an LV apical mass with protruding features. Noncontrast computed tomography confirmed the high-density LV mass (Figure 1B). Coronary angiography revealed mild to moderate coronary atherosclerosis without obstructive coronary artery disease. ### OUTPUT:

Takotsubo cardiomyopathy complicated by hypotension secondary to LV outflow tract obstruction and LV thrombus

['Cardiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy man in his early 70s was referred to our emergency department with exertional dyspnea. He reported recent physical and emotional stress from work and dizziness 2 days prior to presentation. He denied fever or palpitations. His blood pressure was 84/59 mm Hg. A harmonic, musical systolic murmur was heard at the left third intercostal space. An electrocardiogram (ECG; Figure 1A) showed diffuse ST-segment elevation, most prominently in the anterior precordial leads. Laboratory evaluation revealed elevated levels of troponin (1.33 ng/mL; normal range: ≤0.016 ng/mL [to convert to micrograms per liter, multiply by 1.0]), brain natriuretic peptide (376.5 pg/mL; normal range: ≤18.4 pg/mL [to convert to nanograms per liter, multiply by 1.0]), creatinine phosphokinase (96 U/L; normal range: 41-153 U/L), and D-dimer (0.68 μg/mL; normal range: ≤1.00 μg/mL [to convert to nanomoles per liter, multiply by 5.476]). Echocardiography showed left ventricular (LV) wall-motion abnormalities involving the mid and apical segments and an LV apical mass with protruding features. Noncontrast computed tomography confirmed the high-density LV mass (Figure 1B). Coronary angiography revealed mild to moderate coronary atherosclerosis without obstructive coronary artery disease. ### OUTPUT:

JAMA_FINAL209

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old boy with an unsteady gait was referred for evaluation. He had been well until 1 month prior, when he developed lower limb weakness after eating a vegetarian diet for 15 days. His medical and family histories were unremarkable. His walking had become unsteady, and he was less talkative. On examination, he scored 24 on a Mini-Mental State Examination, with impairments in temporal and spatial orientation, calculation, and short-term memory. Horizontal nystagmus was observed. His lower limb strength was 4 of 5 proximally and 5− of 5 distally, with increased muscle tone. Patellar reflexes were brisk. Ankle clonus and Babinski signs were present bilaterally. His gait was spastic (Video). Blood test results indicated normocytic anemia (hemoglobin level, 126 g/L; reference, >130 g/L [to convert to grams per deciliter, multiply by 0.1]), borderline folate elevation (2.15 ng/mL; reference, >2 μg/L [to convert nanomoles per liter, multiply by 2.266]), and an increased homocysteine level (8.85 mg/L; reference, <2.03 mg/L [to convert to micromoles per liter, multiply by 7.397]). Results of stool analysis; liver and kidney function tests; myocardial enzyme, electrolyte, ammonia, trace element, and B12 levels; thyroid function, arterial blood gas, antinuclear antibodies, and intrinsic factor antibody tests; and an infection panel test were unremarkable. Magnetic resonance imaging showed mild cerebral atrophy and a hyperintense T2-weighted signal in the cervical spinal cord. Electromyography results were normal. Electroencephalography showed diffuse background slowing with scattered epileptiform discharges. Urine organic acid analysis indicated methylmalonic acidemia. A serum amino acid analysis was nondiagnostic (Figure 1). Cerebrospinal fluid was normal. ### OUTPUT:

Cobalamin C deficiency

['Neurology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old girl with an unsteady gait was referred for evaluation. She had been well until 1 month prior, when she developed lower limb weakness after eating a vegetarian diet for 15 days. Her medical and family histories were unremarkable. Her walking had become unsteady, and she was less talkative. On examination, she scored 24 on a Mini-Mental State Examination, with impairments in temporal and spatial orientation, calculation, and short-term memory. Horizontal nystagmus was observed. Her lower limb strength was 4 of 5 proximally and 5− of 5 distally, with increased muscle tone. Patellar reflexes were brisk. Ankle clonus and Babinski signs were present bilaterally. Her gait was spastic (Video). Blood test results indicated normocytic anemia (hemoglobin level, 126 g/L; reference, >130 g/L [to convert to grams per deciliter, multiply by 0.1]), borderline folate elevation (2.15 ng/mL; reference, >2 μg/L [to convert nanomoles per liter, multiply by 2.266]), and an increased homocysteine level (8.85 mg/L; reference, <2.03 mg/L [to convert to micromoles per liter, multiply by 7.397]). Results of stool analysis; liver and kidney function tests; myocardial enzyme, electrolyte, ammonia, trace element, and B12 levels; thyroid function, arterial blood gas, antinuclear antibodies, and intrinsic factor antibody tests; and an infection panel test were unremarkable. Magnetic resonance imaging showed mild cerebral atrophy and a hyperintense T2-weighted signal in the cervical spinal cord. Electromyography results were normal. Electroencephalography showed diffuse background slowing with scattered epileptiform discharges. Urine organic acid analysis indicated methylmalonic acidemia. A serum amino acid analysis was nondiagnostic (Figure 1). Cerebrospinal fluid was normal. ### OUTPUT:

JAMA_FINAL210

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 37-year-old man with no history of vision problems presented with subacute loss of vision in his right eye for 1 week. The patient described a paracentral scotoma that progressed to involve central fixation over the course of 3 days. Two weeks earlier, the patient and his children had developed malaise, low-grade fever, and a rash. He worked in the armed services and denied foreign travel, tick bites, or recent immunization. The patient had been evaluated by his primary care clinician and was referred to an ophthalmologist for further evaluation. On examination, his best-corrected visual acuity was 20/70 OD and 20/20 OS. Test results of intraocular pressures, ocular motility, and pupillary reactions were normal. Confrontation visual fields showed inferonasal and central defects in the right eye. External examination revealed a macular rash of the scalp and all 4 extremities, including the soles and palms (Figure 1A). Anterior segment examination was normal. Posterior segment examination revealed irregular, gray-white pigmentation of the temporal macula of the right eye without vitritis, optic nerve edema, or vasculitis (Figure 1B). Ocular coherence tomography (OCT) revealed focal, heterogenous disruption of the inner segment ellipsoid zone without neurosensory detachment. Fluorescein angiography showed late staining at the level of the retinal pigment epithelium (RPE) superotemporal to the fovea. Findings from a dilated fundus examination were normal in the left eye. ### OUTPUT:

Unilateral acute idiopathic maculopathy

['Infectious Diseases', 'Ophthalmology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 37-year-old woman with no history of vision problems presented with subacute loss of vision in her right eye for 1 week. The patient described a paracentral scotoma that progressed to involve central fixation over the course of 3 days. Two weeks earlier, the patient and her children had developed malaise, low-grade fever, and a rash. She worked in the armed services and denied foreign travel, tick bites, or recent immunization. The patient had been evaluated by her primary care clinician and was referred to an ophthalmologist for further evaluation. On examination, her best-corrected visual acuity was 20/70 OD and 20/20 OS. Test results of intraocular pressures, ocular motility, and pupillary reactions were normal. Confrontation visual fields showed inferonasal and central defects in the right eye. External examination revealed a macular rash of the scalp and all 4 extremities, including the soles and palms (Figure 1A). Anterior segment examination was normal. Posterior segment examination revealed irregular, gray-white pigmentation of the temporal macula of the right eye without vitritis, optic nerve edema, or vasculitis (Figure 1B). Ocular coherence tomography (OCT) revealed focal, heterogenous disruption of the inner segment ellipsoid zone without neurosensory detachment. Fluorescein angiography showed late staining at the level of the retinal pigment epithelium (RPE) superotemporal to the fovea. Findings from a dilated fundus examination were normal in the left eye. ### OUTPUT:

JAMA_FINAL211

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 34-year-old woman presented with photophobia in both eyes. Six months earlier while abroad, the patient had bilateral cosmetic iris implants (BrightOcular) placed. The patient had a mild change in refractive error postoperatively and was offered laser in situ keratomileusis surgery for correction. She did not report any other immediate postoperative complications. For 4 weeks before presentation, she had blurred vision of the right eye. Her visual acuity was 20/50 OD and 20/25 OS. Intraocular pressure (IOP) was 31 mm Hg in the right eye and 17 mm Hg in the left. The pupillary reflex could not be visualized secondary to the iris implants. Slitlamp examination revealed trace anterior chamber cell bilaterally with pigmented keratic precipitates. The implants were overlying the iris structures (Figure 1A). Results of an ultrasonographic biomicroscopy are shown in Figure 1B. Posterior examination was limited by the iris implants, but the optic nerve did not reveal edema or hemorrhages. The peripheral retina could not be visualized in either eye. ### OUTPUT:

Uveitis-glaucoma-hyphema syndrome secondary to cosmetic iris implants

['Ophthalmology', 'Cosmetic Medicine, Non-Surgical', 'Intraocular Inflammation', 'Glaucoma']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 34-year-old man presented with photophobia in both eyes. Six months earlier while abroad, the patient had bilateral cosmetic iris implants (BrightOcular) placed. The patient had a mild change in refractive error postoperatively and was offered laser in situ keratomileusis surgery for correction. He did not report any other immediate postoperative complications. For 4 weeks before presentation, he had blurred vision of the right eye. His visual acuity was 20/50 OD and 20/25 OS. Intraocular pressure (IOP) was 31 mm Hg in the right eye and 17 mm Hg in the left. The pupillary reflex could not be visualized secondary to the iris implants. Slitlamp examination revealed trace anterior chamber cell bilaterally with pigmented keratic precipitates. The implants were overlying the iris structures (Figure 1A). Results of an ultrasonographic biomicroscopy are shown in Figure 1B. Posterior examination was limited by the iris implants, but the optic nerve did not reveal edema or hemorrhages. The peripheral retina could not be visualized in either eye. ### OUTPUT:

JAMA_FINAL212

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A White woman in her late 50s with a medical history of osteoporosis, hyperlipidemia, and migraines presented with hematuria. Results of computed tomography (CT) imaging showed an 8×6×5-cm right kidney lesion (Figure 1, A). The patient underwent surgical resection with a right nephrectomy and an apparent diagnosis of angiomyolipoma (AML). One year later, the patient underwent excision of a right iliac wing lesion, and pathologic findings demonstrated xanthoma of bone with sclerosis. Three years after this second surgery, she presented with new abdominal pain. Results of CT imaging revealed a 4.3-cm retrocaval mass at the level of the renal right vein. She underwent surgical resection, and results of pathologic evaluation were consistent with the original tumor. Follow-up CT imaging revealed a 1.2-cm left upper lobe lung nodule and a 0.8-cm right upper lobe lung nodule, as well as a pulmonary embolism and a left 6th rib fracture. These lesions were fluorodeoxyglucose-positron emission tomography avid. The patient denied constitutional symptoms such as fatigue, fever, chills, and night sweats. She underwent bilateral video-assisted thoracoscopic surgery wedge resections of the lung lesions, which were also consistent with the primary tumor. Five years later, the patient (now in her late 60s) presented with multiple left pleural-based lung lesions (Figure 1, B). Results of all laboratory testing were within reference ranges. These pleural-based lesions were resected with left video-assisted thoracoscopic surgery partial pleurectomy, and results of pathologic evaluation were positive for HMB45 and Melan-A. ### OUTPUT:

Epithelioid angiomyolipoma

['Nephrology', 'Urology', 'Urologic Cancer', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A White man in his late 50s with a medical history of osteoporosis, hyperlipidemia, and migraines presented with hematuria. Results of computed tomography (CT) imaging showed an 8×6×5-cm right kidney lesion (Figure 1, A). The patient underwent surgical resection with a right nephrectomy and an apparent diagnosis of angiomyolipoma (AML). One year later, the patient underwent excision of a right iliac wing lesion, and pathologic findings demonstrated xanthoma of bone with sclerosis. Three years after this second surgery, he presented with new abdominal pain. Results of CT imaging revealed a 4.3-cm retrocaval mass at the level of the renal right vein. He underwent surgical resection, and results of pathologic evaluation were consistent with the original tumor. Follow-up CT imaging revealed a 1.2-cm left upper lobe lung nodule and a 0.8-cm right upper lobe lung nodule, as well as a pulmonary embolism and a left 6th rib fracture. These lesions were fluorodeoxyglucose-positron emission tomography avid. The patient denied constitutional symptoms such as fatigue, fever, chills, and night sweats. He underwent bilateral video-assisted thoracoscopic surgery wedge resections of the lung lesions, which were also consistent with the primary tumor. Five years later, the patient (now in his late 60s) presented with multiple left pleural-based lung lesions (Figure 1, B). Results of all laboratory testing were within reference ranges. These pleural-based lesions were resected with left video-assisted thoracoscopic surgery partial pleurectomy, and results of pathologic evaluation were positive for HMB45 and Melan-A. ### OUTPUT:

JAMA_FINAL213

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 70s was referred to our centralized heart failure management program because of New York Heart Association functional class III heart failure with preserved left ventricular systolic function and recurrent hospitalizations for heart failure. Her medical history was remarkable for coronary artery disease after coronary artery bypass grafting, chronic stable angina, severe tricuspid regurgitation, atrial fibrillation, and obesity with a body mass index of 39 (calculated as weight in kilograms divided by height in meters squared). After screening and medication optimization, she underwent successful implantation of a small sensor-pressure device (CardioMEMS; Abbott) into her pulmonary artery without complication. Her home medications included torsemide, metolazone, metoprolol succinate, spironolactone, isosorbide mononitrate, diltiazem, and ranolazine. Her initial postimplantation sensor readings and waveforms are shown in Figure 1A. ### OUTPUT:

Migration of CardioMEMS sensor

['Medical Devices and Equipment', 'Cardiology', 'Heart Failure']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 70s was referred to our centralized heart failure management program because of New York Heart Association functional class III heart failure with preserved left ventricular systolic function and recurrent hospitalizations for heart failure. His medical history was remarkable for coronary artery disease after coronary artery bypass grafting, chronic stable angina, severe tricuspid regurgitation, atrial fibrillation, and obesity with a body mass index of 39 (calculated as weight in kilograms divided by height in meters squared). After screening and medication optimization, he underwent successful implantation of a small sensor-pressure device (CardioMEMS; Abbott) into his pulmonary artery without complication. His home medications included torsemide, metolazone, metoprolol succinate, spironolactone, isosorbide mononitrate, diltiazem, and ranolazine. His initial postimplantation sensor readings and waveforms are shown in Figure 1A. ### OUTPUT:

JAMA_FINAL214

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 42-year-old woman (height, 160 cm; weight, 50 kg) presented with a 3-month history of a clicking sensation and painful swallowing, mainly on the right side, with a sudden onset. She had consulted other physicians, but the cause could not be identified. The symptoms gradually exacerbated, seriously deteriorating her quality of life and causing a 5-kg weight loss. She also experienced insomnia and depression. Antidepressants and psychotherapy, prescribed under the suspicion of a psychogenic cause, did not alleviate her symptoms. She had no relevant medical history and no smoking or drinking history. Cardiovascular, respiratory, and neurological findings were unremarkable. A careful physical examination, with palpation of the hyoid bone and thyroid cartilage region on swallowing, revealed a clear clicking movement and right-sided friction with accompanying pain. However, results of laryngoscopy and other common imaging studies showed no pathology. Hence, to assess the dynamic structural changes during swallowing, we performed swallowing dynamic computed tomography (SD-CT), which can reveal moving structures by creating a dynamic-volume data set during swallowing.1,2 Comparison of the reconstructed SD-CT images at rest (Figure 1A) and on swallowing (Figure 1B) revealed that the superior thyroid notch and the right superior border of the thyroid cartilage contacted the hyoid bone internally during maximum laryngeal elevation on swallowing. ### OUTPUT:

Clicking larynx

['Otolaryngology', 'Swallowing and Dysphagia']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 42-year-old man (height, 160 cm; weight, 50 kg) presented with a 3-month history of a clicking sensation and painful swallowing, mainly on the right side, with a sudden onset. He had consulted other physicians, but the cause could not be identified. The symptoms gradually exacerbated, seriously deteriorating his quality of life and causing a 5-kg weight loss. He also experienced insomnia and depression. Antidepressants and psychotherapy, prescribed under the suspicion of a psychogenic cause, did not alleviate his symptoms. He had no relevant medical history and no smoking or drinking history. Cardiovascular, respiratory, and neurological findings were unremarkable. A careful physical examination, with palpation of the hyoid bone and thyroid cartilage region on swallowing, revealed a clear clicking movement and right-sided friction with accompanying pain. However, results of laryngoscopy and other common imaging studies showed no pathology. Hence, to assess the dynamic structural changes during swallowing, we performed swallowing dynamic computed tomography (SD-CT), which can reveal moving structures by creating a dynamic-volume data set during swallowing.1,2 Comparison of the reconstructed SD-CT images at rest (Figure 1A) and on swallowing (Figure 1B) revealed that the superior thyroid notch and the right superior border of the thyroid cartilage contacted the hyoid bone internally during maximum laryngeal elevation on swallowing. ### OUTPUT:

JAMA_FINAL215

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 26-year-old man presented with reduced visual acuity in both eyes since early childhood. He had short stature (1.52 m [−3.6 SD]) and progeroid appearance. His parents and brother had normal stature. His medical history was significant for frequent upper respiratory tract infections since infancy. He had no intellectual disability, neurologic symptoms, or hearing impairment. There was no family history of visual impairment or neurologic disorders. His best-corrected visual acuity was 20/80 OD and 20/50 OS. Intraocular pressure was normal. He could not identify any Ishihara color plate. Slitlamp examination was unremarkable. Dilated fundus examination results showed diffuse optic atrophy (OA) and fine pigmentary mottling changes at the fovea in both eyes (Figure 1A). Electroretinography (ERG) showed normal dark-adapted responses and severely reduced light-adapted responses. Optical coherence tomography showed thinning of retinal nerve fiber layers and disruption of outer nuclear layers and the ellipsoid zone at the center of the fovea (Figure 1B). Leber hereditary optic neuropathy sequencing was negative for 3 hot spot mutations. ### OUTPUT:

Short stature, OA, Pelger-Huët anomaly syndrome

['Retinal Disorders', 'Ophthalmology', 'Macular Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 26-year-old woman presented with reduced visual acuity in both eyes since early childhood. She had short stature (1.52 m [−3.6 SD]) and progeroid appearance. Her parents and brother had normal stature. Her medical history was significant for frequent upper respiratory tract infections since infancy. She had no intellectual disability, neurologic symptoms, or hearing impairment. There was no family history of visual impairment or neurologic disorders. Her best-corrected visual acuity was 20/80 OD and 20/50 OS. Intraocular pressure was normal. She could not identify any Ishihara color plate. Slitlamp examination was unremarkable. Dilated fundus examination results showed diffuse optic atrophy (OA) and fine pigmentary mottling changes at the fovea in both eyes (Figure 1A). Electroretinography (ERG) showed normal dark-adapted responses and severely reduced light-adapted responses. Optical coherence tomography showed thinning of retinal nerve fiber layers and disruption of outer nuclear layers and the ellipsoid zone at the center of the fovea (Figure 1B). Leber hereditary optic neuropathy sequencing was negative for 3 hot spot mutations. ### OUTPUT:

JAMA_FINAL216

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 50s presented with a history of pruritic lesions of the lower legs over the past 15 years that were unresponsive to topical corticosteroid therapy. On examination, he had multiple lichenified and ulcerated papules and nodules, some of them grouped in plaques located on the medial aspect of both shins (Figure, A). Occasional tense blisters were also seen (Figure, B). The patient’s family history was significant for similar cutaneous lesions in his father, brother, and cousin. Mild toenail dystrophy was also observed. A punch biopsy from the shin for histopathologic examination was performed (Figure, C and D). ### OUTPUT:

Pretibial epidermolysis bullosa

['Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 50s presented with a history of pruritic lesions of the lower legs over the past 15 years that were unresponsive to topical corticosteroid therapy. On examination, she had multiple lichenified and ulcerated papules and nodules, some of them grouped in plaques located on the medial aspect of both shins (Figure, A). Occasional tense blisters were also seen (Figure, B). The patient’s family history was significant for similar cutaneous lesions in her father, brother, and cousin. Mild toenail dystrophy was also observed. A punch biopsy from the shin for histopathologic examination was performed (Figure, C and D). ### OUTPUT:

JAMA_FINAL217

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old man presented with worsening right eye pain and purulent discharge. He reported being hit in the face by a tree branch several days prior. His medical history was notable for HIV, with a last known CD4 lymphocyte count of 112 cells/mm3 and variable adherence to antiretroviral therapy. At an outside hospital, cultures were obtained, and treatment was initiated with ofloxacin eye drops, 0.3%, ciprofloxacin hydrochloride ointment, 0.3%, and oral moxifloxacin hydrochloride, 400 mg daily. His symptoms worsened, and he was referred 3 days later for further evaluation. On examination, visual acuity in the right eye was hand motions. The left eye examination results were unremarkable. Slitlamp examination was limited by patient discomfort but revealed purulent discharge, a markedly inflamed conjunctiva, diffuse cornea opacification and thinning, and a flat anterior chamber. Given the history of tree branch trauma, the patient was brought to the operating room. Intraoperatively, a 0.5-mm corneal perforation was identified within an area of thinning (Figure, A). Microbial cultures were repeated, and corneal glue was applied. Gram stain of the purulent discharge demonstrated numerous polymorphonuclear leukocytes only. All subsequent microbiology cultures were negative. Despite treatment with topical fortified vancomycin, 25 mg/mL, tobramycin, 13.3 mg/mL, intravenous levofloxacin, 750 mg daily, and doxycycline, 100 mg twice daily, the purulent conjunctivitis and corneal stromal necrosis did not improve (Figure, B). ### OUTPUT:

Gonococcal keratoconjunctivitis

['Cornea', 'Sexually Transmitted Infections', 'External Eye Disease', 'Ophthalmology', 'HIV']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old woman presented with worsening right eye pain and purulent discharge. She reported being hit in the face by a tree branch several days prior. Her medical history was notable for HIV, with a last known CD4 lymphocyte count of 112 cells/mm3 and variable adherence to antiretroviral therapy. At an outside hospital, cultures were obtained, and treatment was initiated with ofloxacin eye drops, 0.3%, ciprofloxacin hydrochloride ointment, 0.3%, and oral moxifloxacin hydrochloride, 400 mg daily. Her symptoms worsened, and she was referred 3 days later for further evaluation. On examination, visual acuity in the right eye was hand motions. The left eye examination results were unremarkable. Slitlamp examination was limited by patient discomfort but revealed purulent discharge, a markedly inflamed conjunctiva, diffuse cornea opacification and thinning, and a flat anterior chamber. Given the history of tree branch trauma, the patient was brought to the operating room. Intraoperatively, a 0.5-mm corneal perforation was identified within an area of thinning (Figure, A). Microbial cultures were repeated, and corneal glue was applied. Gram stain of the purulent discharge demonstrated numerous polymorphonuclear leukocytes only. All subsequent microbiology cultures were negative. Despite treatment with topical fortified vancomycin, 25 mg/mL, tobramycin, 13.3 mg/mL, intravenous levofloxacin, 750 mg daily, and doxycycline, 100 mg twice daily, the purulent conjunctivitis and corneal stromal necrosis did not improve (Figure, B). ### OUTPUT:

JAMA_FINAL218

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 67-year-old woman with fibromyalgia presented with sequential bilateral vision loss. Vision decreased suddenly in the right eye 3 to 4 weeks prior and in the left eye 5 days prior. She reported left-sided scalp tenderness; jaw claudication; neck, shoulder, and low back pain; and a recent 6.8-kilogram weight loss. Visual acuity was 20/200 in the right eye (OD) and hand motion in the left eye (OS). She had a left relative afferent pupillary defect, moderate dry-eye syndrome, and mild cataracts. The right optic nerve had a cup-disc ratio of 0.55 with temporal pallor and mild optic disc edema, and the left nerve had a cup-disc ratio of 0.50 with mild edema without pallor. Bilateral arteritic anterior ischemic optic neuropathy was suspected. Expedited evaluation and treatment of giant cell arteritis (GCA) was pursued. Erythrocyte sedimentation rate (ESR) was elevated at 61 mm/h, whereas C-reactive protein (CRP), hemoglobin, and platelet levels were normal. She was hospitalized for empirical treatment with 1 g of intravenous methylprednisolone sodium succinate daily for 5 days. Results of a left temporal artery biopsy (TAB) were negative for GCA. Magnetic resonance imaging of the brain and orbits showed abnormal signal and contrast enhancement within the intraorbital midportion of both optic nerves (Figure 1A and B) as well as incidental parotid gland cysts bilaterally (Figure 1C). She was discharged and was taking oral prednisone anhydrous, 60 mg daily. One month later the patient had improvement in visual acuity to 20/50 OD and 20/25 OS. ### OUTPUT:

Neuromyelitis optica spectrum disorder associated with Sjögren syndrome

['Demyelinating Disorders', 'Neurology', 'Neuromyelitis Optica', 'Ophthalmology', 'Rheumatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 67-year-old man with fibromyalgia presented with sequential bilateral vision loss. Vision decreased suddenly in the right eye 3 to 4 weeks prior and in the left eye 5 days prior. He reported left-sided scalp tenderness; jaw claudication; neck, shoulder, and low back pain; and a recent 6.8-kilogram weight loss. Visual acuity was 20/200 in the right eye (OD) and hand motion in the left eye (OS). He had a left relative afferent pupillary defect, moderate dry-eye syndrome, and mild cataracts. The right optic nerve had a cup-disc ratio of 0.55 with temporal pallor and mild optic disc edema, and the left nerve had a cup-disc ratio of 0.50 with mild edema without pallor. Bilateral arteritic anterior ischemic optic neuropathy was suspected. Expedited evaluation and treatment of giant cell arteritis (GCA) was pursued. Erythrocyte sedimentation rate (ESR) was elevated at 61 mm/h, whereas C-reactive protein (CRP), hemoglobin, and platelet levels were normal. He was hospitalized for empirical treatment with 1 g of intravenous methylprednisolone sodium succinate daily for 5 days. Results of a left temporal artery biopsy (TAB) were negative for GCA. Magnetic resonance imaging of the brain and orbits showed abnormal signal and contrast enhancement within the intraorbital midportion of both optic nerves (Figure 1A and B) as well as incidental parotid gland cysts bilaterally (Figure 1C). He was discharged and was taking oral prednisone anhydrous, 60 mg daily. One month later the patient had improvement in visual acuity to 20/50 OD and 20/25 OS. ### OUTPUT:

JAMA_FINAL219

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 64-year-old woman in excellent general health who was not taking any medications was referred for evaluation of an epiretinal membrane of her right eye. She reported no blurry vision, metamorphopsia, photopsias, floaters, or nyctalopia, and she had no history of refractive surgical procedures, ocular surgical procedures, or trauma. Her family history was negative for ocular conditions, and there was no consanguinity in her family. Her visual acuity was 20/20 OU with correction (plano +0.25 × 153 OD and −0.50 + 0.25 × 009 OS). External and anterior segment examination results were unremarkable except for mild nuclear sclerotic cataracts. Results of a dilated ophthalmoscopic examination showed radial spokelike striae of the fovea, with a central cyst in the right eye and macular edema of the left eye. Optical coherence tomography (OCT) imaging of the right macula showed cystlike changes in the outer retina in the foveal and parafoveal regions and in the inner retina in the temporal macula. Optical coherence tomography imaging of the left macula showed cystlike changes in the outer retina in the inferior macula (Figure). Of note, OCT scans of the optic nerves did not reveal an optic disc pit. ### OUTPUT:

Stellate nonhereditary idiopathic foveomacular retinoschisis

['Ophthalmology', 'Retinal Disorders', 'Macular Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 64-year-old man in excellent general health who was not taking any medications was referred for evaluation of an epiretinal membrane of his right eye. He reported no blurry vision, metamorphopsia, photopsias, floaters, or nyctalopia, and he had no history of refractive surgical procedures, ocular surgical procedures, or trauma. His family history was negative for ocular conditions, and there was no consanguinity in his family. His visual acuity was 20/20 OU with correction (plano +0.25 × 153 OD and −0.50 + 0.25 × 009 OS). External and anterior segment examination results were unremarkable except for mild nuclear sclerotic cataracts. Results of a dilated ophthalmoscopic examination showed radial spokelike striae of the fovea, with a central cyst in the right eye and macular edema of the left eye. Optical coherence tomography (OCT) imaging of the right macula showed cystlike changes in the outer retina in the foveal and parafoveal regions and in the inner retina in the temporal macula. Optical coherence tomography imaging of the left macula showed cystlike changes in the outer retina in the inferior macula (Figure). Of note, OCT scans of the optic nerves did not reveal an optic disc pit. ### OUTPUT:

JAMA_FINAL220

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 54-year-old woman with a medical history of hypertension, hyperlipidemia, and migraines presented to a tertiary care otolaryngology clinic reporting 3 months of worsening right ear pain and 1 month of pulsatile tinnitus and hearing loss. She denied a history of fever, otorrhea, prior ear infections, vertigo, or otologic surgery. The patient first saw her primary care physician, who visualized a mass in the right ear canal and attempted needle aspiration, which led to self-resolved bleeding. She was given ciprofloxacin ear drops and trimethoprim/sulfamethoxazole, which did not improve her symptoms. On examination, her right external auditory canal (EAC) was completely obstructed by a fleshy, pulsatile mass with a red hue (Figure 1A). Results of Weber tuning fork examination lateralized to the right ear and a Rinne examination suggested a conductive hearing loss. Formal audiogram results confirmed conductive hearing loss in the right ear and type B tympanometry, which was indicative of poor eardrum mobility. Computed tomography (CT) of the temporal bone without contrast showed a well-circumscribed 9-mm lesion in the EAC with bony erosion along the junction of the anterior wall and floor (Figure 1, B and C). Magnetic resonance imaging results showed a well-circumscribed, contrast-enhancing mass that was confined to the EAC (Figure 1D). ### OUTPUT:

Lobular capillary hemangioma of the EAC

['Otolaryngology', 'Otology', 'Audiology and Hearing']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 54-year-old man with a medical history of hypertension, hyperlipidemia, and migraines presented to a tertiary care otolaryngology clinic reporting 3 months of worsening right ear pain and 1 month of pulsatile tinnitus and hearing loss. He denied a history of fever, otorrhea, prior ear infections, vertigo, or otologic surgery. The patient first saw his primary care physician, who visualized a mass in the right ear canal and attempted needle aspiration, which led to self-resolved bleeding. He was given ciprofloxacin ear drops and trimethoprim/sulfamethoxazole, which did not improve his symptoms. On examination, his right external auditory canal (EAC) was completely obstructed by a fleshy, pulsatile mass with a red hue (Figure 1A). Results of Weber tuning fork examination lateralized to the right ear and a Rinne examination suggested a conductive hearing loss. Formal audiogram results confirmed conductive hearing loss in the right ear and type B tympanometry, which was indicative of poor eardrum mobility. Computed tomography (CT) of the temporal bone without contrast showed a well-circumscribed 9-mm lesion in the EAC with bony erosion along the junction of the anterior wall and floor (Figure 1, B and C). Magnetic resonance imaging results showed a well-circumscribed, contrast-enhancing mass that was confined to the EAC (Figure 1D). ### OUTPUT:

JAMA_FINAL221

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 14-month-old boy presented with a sudden-onset, rapidly enlarging lesion in the right eye detected by his parents 2 weeks earlier. The patient had normal tracking bilaterally. Under anesthesia, findings from an examination of the right eye revealed an inferonasal translucent gray-white iris mass with numerous intralesional lacy cystic structures (Figure 1). There was no microphthalmia, cataract, lens subluxation, anterior or posterior synechiae, glaucoma, or uveitis. Findings from a fundus examination were normal. High-resolution anterior segment echography results revealed an iridociliary mass that extended posteriorly to the pars plicata with overall dimensions of 7.7 × 6.0 × 1.9 mm. There were no associated calcifications, retrolental membranes, or seeding. ### OUTPUT:

Iridociliary medulloepithelioma

['Ophthalmology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 14-month-old girl presented with a sudden-onset, rapidly enlarging lesion in the right eye detected by her parents 2 weeks earlier. The patient had normal tracking bilaterally. Under anesthesia, findings from an examination of the right eye revealed an inferonasal translucent gray-white iris mass with numerous intralesional lacy cystic structures (Figure 1). There was no microphthalmia, cataract, lens subluxation, anterior or posterior synechiae, glaucoma, or uveitis. Findings from a fundus examination were normal. High-resolution anterior segment echography results revealed an iridociliary mass that extended posteriorly to the pars plicata with overall dimensions of 7.7 × 6.0 × 1.9 mm. There were no associated calcifications, retrolental membranes, or seeding. ### OUTPUT:

JAMA_FINAL222

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 80s with a history of asthma and bronchiectasis who was receiving immunosuppression therapy presented to an outside hospital with dyspnea and right arm swelling and tenderness 8 days before transfer to our center. The immunosuppression therapy consisted of methylprednisolone, 12 mg every other day, and the patient’s medical history included cerebrovascular accident, atrial flutter, and aortic stenosis. On initial evaluation, his vital signs were stable. On physical examination, the patient had edema of the right arm, hand, and fingers with overlying diffuse violaceous nonblanching and edematous nodules (Figure, A). Purpuric plaques were also noted on the right cheek, central chest, left arm, and left posterior shoulder. Laboratory findings were significant for a hemoglobin level of 8.6 g/dL (reference range 13.5-17.5 g/dL [to convert to g/L, multiply by 10]). Results of blood cultures from the outside hospital showed “yeast” at the time of transfer. ### OUTPUT:

Disseminated protothecosis

['Dermatology', 'Geriatrics', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 80s with a history of asthma and bronchiectasis who was receiving immunosuppression therapy presented to an outside hospital with dyspnea and right arm swelling and tenderness 8 days before transfer to our center. The immunosuppression therapy consisted of methylprednisolone, 12 mg every other day, and the patient’s medical history included cerebrovascular accident, atrial flutter, and aortic stenosis. On initial evaluation, her vital signs were stable. On physical examination, the patient had edema of the right arm, hand, and fingers with overlying diffuse violaceous nonblanching and edematous nodules (Figure, A). Purpuric plaques were also noted on the right cheek, central chest, left arm, and left posterior shoulder. Laboratory findings were significant for a hemoglobin level of 8.6 g/dL (reference range 13.5-17.5 g/dL [to convert to g/L, multiply by 10]). Results of blood cultures from the outside hospital showed “yeast” at the time of transfer. ### OUTPUT:

JAMA_FINAL223

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old woman was referred for symptoms of painless and progressive bilateral loss of central and peripheral vision over the last 6 months, associated with floaters in the left eye. The patient reported difficulty in performing essential daily tasks, such as driving and walking without assistance. She denied photopsias. Her previous ocular and medical history were unremarkable. She denied any systemic symptoms as well as any family history of inherited ocular diseases. On examination, best-corrected visual acuity was 20/32 OU. Fundus examination results showed attenuated arterial and venous retinal vessels and slight retinal pigmented epithelium changes at the posterior pole, consisting of atrophy and pigment migration in both eyes, associated with vitreous opacities in the left eye. Fluorescein angiography examination results showed a mild leakage of arterial and venous retinal vasculature (Figure). Spectral-domain optical coherence tomography exhibited disruption at the photoreceptor level and multifocal hyperreflective material depositions at the retinal pigmented epithelium level. ### OUTPUT:

Paraneoplastic autoimmune retinopathy

['Gastroenterology', 'Gastrointestinal Cancer', 'Oncology', 'Ophthalmology', 'Gastric Cancer']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 65-year-old man was referred for symptoms of painless and progressive bilateral loss of central and peripheral vision over the last 6 months, associated with floaters in the left eye. The patient reported difficulty in performing essential daily tasks, such as driving and walking without assistance. He denied photopsias. His previous ocular and medical history were unremarkable. He denied any systemic symptoms as well as any family history of inherited ocular diseases. On examination, best-corrected visual acuity was 20/32 OU. Fundus examination results showed attenuated arterial and venous retinal vessels and slight retinal pigmented epithelium changes at the posterior pole, consisting of atrophy and pigment migration in both eyes, associated with vitreous opacities in the left eye. Fluorescein angiography examination results showed a mild leakage of arterial and venous retinal vasculature (Figure). Spectral-domain optical coherence tomography exhibited disruption at the photoreceptor level and multifocal hyperreflective material depositions at the retinal pigmented epithelium level. ### OUTPUT:

JAMA_FINAL224

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 30s undergoing peritoneal dialysis for kidney failure who was also being investigated for severe hyperparathyroidism presented with multiple skin lesions 1 day after undergoing cervical computed tomography with iodinated contrast. Physical examination revealed a polymorphous cutaneous eruption characterized by nodular vegetating lesions on the lower lip and right nasal ala (Figure 1A); papulovesicular lesions, either umbilicated or with an erosive center, clustered on the left cheek (Figure 1B); and 2 papulovesicular lesions with an erythematous-to-violaceous halo at the cannula insertion sites on the back of the right hand and the inner side of the wrist. The patient reported that the lesions were painful, with the ones in the oral mucosa impairing feeding. ### OUTPUT:

Iododerma

['Nephrology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 30s undergoing peritoneal dialysis for kidney failure who was also being investigated for severe hyperparathyroidism presented with multiple skin lesions 1 day after undergoing cervical computed tomography with iodinated contrast. Physical examination revealed a polymorphous cutaneous eruption characterized by nodular vegetating lesions on the lower lip and right nasal ala (Figure 1A); papulovesicular lesions, either umbilicated or with an erosive center, clustered on the left cheek (Figure 1B); and 2 papulovesicular lesions with an erythematous-to-violaceous halo at the cannula insertion sites on the back of the right hand and the inner side of the wrist. The patient reported that the lesions were painful, with the ones in the oral mucosa impairing feeding. ### OUTPUT:

JAMA_FINAL225

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-50s with a medical history significant for pulmonary embolism 10 years prior (previously receiving anticoagulation therapy) presented to the emergency department with 10 days of progressively worsening, sharp, nonradiating chest pain. The pain was present at rest, 7 of 10 in severity, and worse with inspiration. He experienced concomitant exertional shortness of breath, dry cough, and lightheadedness. His cardiac history was otherwise unremarkable. Family history was notable for breast cancer in his mother and his sister, but no known inherited hypercoagulable disorders. In the emergency department, his vital signs were as follows: temperature 37.0 °C, blood pressure 130/76 mm Hg, heart rate 97/min, respiratory rate 16/min, and oxygen saturation of 95% on room air. Physical examination results were unremarkable, with no cardiac murmurs, rubs, pulmonary crackles, jugular venous distention, or lower extremity edema. Laboratory test results were remarkable for an elevated D-dimer level, an elevated C-reactive protein level and erythrocyte sedimentation rate, and a mildly elevated pro-BNP level, but normal levels of troponin and procalcitonin. An electrocardiogram showed normal sinus rhythm with evidence of right heart strain, and a computed tomography angiogram of the chest demonstrated an occlusive pulmonary embolism of the left main pulmonary artery and several peripheral consolidations in the left lower lung field consistent with infarction. The patient started anticoagulation therapy with intravenous heparin. A subsequent echocardiogram revealed bowing of the interventricular septum into the left ventricle and a very large (6.6 × 4.1-cm), mobile, nonhomogeneous, pedunculated mass straddling the tricuspid valve and moving between the right atrium and right ventricle (Figure 1 and Video). ### OUTPUT:

Right atrial myxoma with partial myxomatous embolism to the pulmonary artery

['Cardiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-50s with a medical history significant for pulmonary embolism 10 years prior (previously receiving anticoagulation therapy) presented to the emergency department with 10 days of progressively worsening, sharp, nonradiating chest pain. The pain was present at rest, 7 of 10 in severity, and worse with inspiration. She experienced concomitant exertional shortness of breath, dry cough, and lightheadedness. Her cardiac history was otherwise unremarkable. Family history was notable for breast cancer in her mother and her sister, but no known inherited hypercoagulable disorders. In the emergency department, her vital signs were as follows: temperature 37.0 °C, blood pressure 130/76 mm Hg, heart rate 97/min, respiratory rate 16/min, and oxygen saturation of 95% on room air. Physical examination results were unremarkable, with no cardiac murmurs, rubs, pulmonary crackles, jugular venous distention, or lower extremity edema. Laboratory test results were remarkable for an elevated D-dimer level, an elevated C-reactive protein level and erythrocyte sedimentation rate, and a mildly elevated pro-BNP level, but normal levels of troponin and procalcitonin. An electrocardiogram showed normal sinus rhythm with evidence of right heart strain, and a computed tomography angiogram of the chest demonstrated an occlusive pulmonary embolism of the left main pulmonary artery and several peripheral consolidations in the left lower lung field consistent with infarction. The patient started anticoagulation therapy with intravenous heparin. A subsequent echocardiogram revealed bowing of the interventricular septum into the left ventricle and a very large (6.6 × 4.1-cm), mobile, nonhomogeneous, pedunculated mass straddling the tricuspid valve and moving between the right atrium and right ventricle (Figure 1 and Video). ### OUTPUT:

JAMA_FINAL226

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old man was referred to the eye clinic for unilateral uveitis and 2 days of sudden vision loss in his right eye. He reported experiencing light sensitivity and mild eye pain. He was in otherwise good health without any chronic medical problems. He reported receiving anticoagulation therapy in the past for a mitral valve problem. His visual acuity was 20/200 OD and 20/20 OS. The examination of the left eye was unremarkable. Slitlamp examination of his right eye revealed 3+ anterior chamber inflammation with vitreous cells. An examination of the dilated fundus showed optic nerve edema with an overlying white infiltrate. In addition, there was inferior retinal whitening consistent with an artery occlusion (Figure 1A). The whitening was attributable to inner retina ischemia, with sparing in the distribution of the cilioretinal artery. An inferior hemicentral retinal artery occlusion was confirmed on intravenous fluorescein angiography (Figure 1B). No embolus was noted at any retinal artery branch points. Notably, a dog bit the patient’s hand 2 months before presentation. Since that time, the patient developed a persistent cough, night sweats, and low-grade fevers that were treated unsuccessfully with 2 courses of oral antibiotics. ### OUTPUT:

Hemicentral retinal artery occlusion secondary to septic embolus

['Cardiology', 'Emergency Medicine', 'Infectious Diseases', 'Trauma and Injury', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old woman was referred to the eye clinic for unilateral uveitis and 2 days of sudden vision loss in her right eye. She reported experiencing light sensitivity and mild eye pain. She was in otherwise good health without any chronic medical problems. She reported receiving anticoagulation therapy in the past for a mitral valve problem. Her visual acuity was 20/200 OD and 20/20 OS. The examination of the left eye was unremarkable. Slitlamp examination of her right eye revealed 3+ anterior chamber inflammation with vitreous cells. An examination of the dilated fundus showed optic nerve edema with an overlying white infiltrate. In addition, there was inferior retinal whitening consistent with an artery occlusion (Figure 1A). The whitening was attributable to inner retina ischemia, with sparing in the distribution of the cilioretinal artery. An inferior hemicentral retinal artery occlusion was confirmed on intravenous fluorescein angiography (Figure 1B). No embolus was noted at any retinal artery branch points. Notably, a dog bit the patient’s hand 2 months before presentation. Since that time, the patient developed a persistent cough, night sweats, and low-grade fevers that were treated unsuccessfully with 2 courses of oral antibiotics. ### OUTPUT:

JAMA_FINAL227

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old woman with metastatic, well-differentiated, small intestinal neuroendocrine tumor (NET) presented for routine follow-up in September 2020 with worsening fatigue and flushing. She was initially diagnosed with metastatic involvement of the liver, bone, and intra-abdominal lymph nodes in 2015 and received 3 treatments with peptide receptor radionuclide therapy (PRRT) in 2017. After 2 years of disease stability she was retreated with PRRT in November 2019 because of radiographic progression of disease and worsening symptoms. A third dose of PRRT was given in March 2020; a fourth was deferred owing to persistent thrombocytopenia after treatment. Gallium 68 dotatate positron emission tomography–computed tomography in July 2020 revealed stable disease (Figure, A). ### OUTPUT:

Neuroendocrine tumor infiltration of bone marrow

['Oncology', 'Pathology and Laboratory Medicine', 'Hematology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 72-year-old man with metastatic, well-differentiated, small intestinal neuroendocrine tumor (NET) presented for routine follow-up in September 2020 with worsening fatigue and flushing. He was initially diagnosed with metastatic involvement of the liver, bone, and intra-abdominal lymph nodes in 2015 and received 3 treatments with peptide receptor radionuclide therapy (PRRT) in 2017. After 2 years of disease stability he was retreated with PRRT in November 2019 because of radiographic progression of disease and worsening symptoms. A third dose of PRRT was given in March 2020; a fourth was deferred owing to persistent thrombocytopenia after treatment. Gallium 68 dotatate positron emission tomography–computed tomography in July 2020 revealed stable disease (Figure, A). ### OUTPUT:

JAMA_FINAL228

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s presented to our dermatology outpatient department with a 5-year history of pruritic papules on the right side of his lower back. He was otherwise healthy, with no family history of a similar condition. Physical examination results showed multiple dome-shaped, skin-colored, firm papules on his right lower back, arranged in a blaschkoid distribution (Figure 1A). The lesions varied in size, with some coalescing into irregular-shaped, larger papules. Telangiectasis could be seen on some of the lesions. A skin biopsy was performed on his back and submitted for further histopathologic analysis (Figure 1B and C). ### OUTPUT:

Mucinous nevus

['Dermatology', 'Nevi']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s presented to our dermatology outpatient department with a 5-year history of pruritic papules on the right side of her lower back. She was otherwise healthy, with no family history of a similar condition. Physical examination results showed multiple dome-shaped, skin-colored, firm papules on her right lower back, arranged in a blaschkoid distribution (Figure 1A). The lesions varied in size, with some coalescing into irregular-shaped, larger papules. Telangiectasis could be seen on some of the lesions. A skin biopsy was performed on her back and submitted for further histopathologic analysis (Figure 1B and C). ### OUTPUT:

JAMA_FINAL229

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 50-year-old woman presented with left eye redness and headaches for 2 months. Results from a previous computed tomographic scan of the head were unremarkable. She denied ocular disease, trauma, or surgery. She had no medical problems aside from chronic back pain due to a herniated disc. Her best-corrected visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure, extraocular motility, and pupillary examination results were normal. The right eye was unremarkable. Examination of the left eye showed 2 temporal scleral nodules with surrounding hyperemia and no scleromalacia. She experienced substantial pain with palpation. Posterior examination results were unremarkable. The results of the following laboratory tests were all unremarkable: tuberculosis interferon-γ release assay, rapid plasma reagin, fluorescent treponemal antibody, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme. The rheumatoid factor level (18 IU/mL [normal range, <14 IU/mL]) and C-reactive protein level (26 mg/L [normal range, 0-5 mg/L]) were elevated. In addition, Lyme IgG, IgM, and reflex Western blot assays were positive for antibodies. The patient denied travel to Lyme-endemic regions, tick bites, or rashes. The patient started oral prednisone therapy for possible rheumatoid arthritis (RA)–associated nodular scleritis, doxycycline therapy for positive Lyme studies, and was referred to a rheumatologist for further RA evaluation. Two weeks after presentation and initiation of oral prednisone therapy, the patient noted improvement in pain, but the scleral nodules and hyperemia persisted. Therefore, subconjunctival triamcinolone acetonide (0.5 mL of 40 mg/mL) was administered to the left eye. Further confirmatory RA workup by rheumatology did not reveal other systemic findings thought to be associated with RA on review of symptoms or clinical examination. The patient's back pain was associated with her herniated disc. Subsequently, the patient’s examination results showed new scleral thinning of the left eye with persistence of the scleral nodules (Figure 1). ### OUTPUT:

Mycobacterium infectious scleritis

['Ophthalmology', 'Intraocular Inflammation', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 50-year-old man presented with left eye redness and headaches for 2 months. Results from a previous computed tomographic scan of the head were unremarkable. He denied ocular disease, trauma, or surgery. He had no medical problems aside from chronic back pain due to a herniated disc. His best-corrected visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure, extraocular motility, and pupillary examination results were normal. The right eye was unremarkable. Examination of the left eye showed 2 temporal scleral nodules with surrounding hyperemia and no scleromalacia. He experienced substantial pain with palpation. Posterior examination results were unremarkable. The results of the following laboratory tests were all unremarkable: tuberculosis interferon-γ release assay, rapid plasma reagin, fluorescent treponemal antibody, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme. The rheumatoid factor level (18 IU/mL [normal range, <14 IU/mL]) and C-reactive protein level (26 mg/L [normal range, 0-5 mg/L]) were elevated. In addition, Lyme IgG, IgM, and reflex Western blot assays were positive for antibodies. The patient denied travel to Lyme-endemic regions, tick bites, or rashes. The patient started oral prednisone therapy for possible rheumatoid arthritis (RA)–associated nodular scleritis, doxycycline therapy for positive Lyme studies, and was referred to a rheumatologist for further RA evaluation. Two weeks after presentation and initiation of oral prednisone therapy, the patient noted improvement in pain, but the scleral nodules and hyperemia persisted. Therefore, subconjunctival triamcinolone acetonide (0.5 mL of 40 mg/mL) was administered to the left eye. Further confirmatory RA workup by rheumatology did not reveal other systemic findings thought to be associated with RA on review of symptoms or clinical examination. The patient's back pain was associated with his herniated disc. Subsequently, the patient’s examination results showed new scleral thinning of the left eye with persistence of the scleral nodules (Figure 1). ### OUTPUT:

JAMA_FINAL230

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 20s presented to the emergency department with presyncope, hives, and nausea after walking outside in the cold. On arrival, their pulse was 120 beats per minute; blood pressure, 85/52 mm Hg; respiratory rate, 20 breaths per minute; oxygen saturation, 100% with a nonrebreather mask; and temperature, 36.8° C. The patient was in moderate respiratory distress, and chest auscultation revealed bilateral wheezing. They were treated for presumed anaphylaxis with 0.5 mg of epinephrine intramuscularly. Immediately after the administration of epinephrine, they developed a headache, nausea, and chest pain. A 12-lead electrocardiogram (ECG) was obtained 5 minutes later (Figure 1). The patient had persistent hypotension. ### OUTPUT:

Kounis syndrome (acute coronary vasospasm associated with anaphylactoid response)

['Cardiology', 'Pain Medicine', 'Allergy and Clinical Immunology', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their 20s presented to the emergency department with presyncope, hives, and nausea after walking outside in the cold. On arrival, her pulse was 120 beats per minute; blood pressure, 85/52 mm Hg; respiratory rate, 20 breaths per minute; oxygen saturation, 100% with a nonrebreather mask; and temperature, 36.8° C. The patient was in moderate respiratory distress, and chest auscultation revealed bilateral wheezing. She was treated for presumed anaphylaxis with 0.5 mg of epinephrine intramuscularly. Immediately after the administration of epinephrine, she developed a headache, nausea, and chest pain. A 12-lead electrocardiogram (ECG) was obtained 5 minutes later (Figure 1). The patient had persistent hypotension. ### OUTPUT:

JAMA_FINAL231

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 73-year-old man was referred to our service for assessment of a slow-growing conjunctival lesion in the left eye. He had first noticed left eye discomfort and a fullness of the left lower eyelid 3 months previously. He denied any vision or systemic symptoms. His ophthalmic history was noncontributory. The patient’s medical history was notable only for prostate carcinoma, which was treated with radiotherapy 12 years ago. On examination, his visual acuities were 20/25 OU. Slitlamp examination of the anterior segment revealed diffuse yellow-pink polypoidal papules affecting the inferior fornix and inferior palpebral conjunctiva of the left eye (Figure 1A). The upper palpebral conjunctiva in the left eye had a velvety yellow appearance (Figure 1B). The remainder of the examination of both eyes was unremarkable. Initial investigations, including a complete blood cell count, urinalysis, and measurement of inflammatory markers, kidney function, and prostate-specific antigen level, were within normal limits. Serum electrophoresis showed raised monoclonal IgM bands (7.25 g/L; reference range, 0.50-2.00 g/L) with a κ/λ light-chain ratio of 2.92 (reference range, 0.260-1.65). ### OUTPUT:

Conjunctival amyloidosis

['External Eye Disease', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 73-year-old woman was referred to our service for assessment of a slow-growing conjunctival lesion in the left eye. She had first noticed left eye discomfort and a fullness of the left lower eyelid 3 months previously. She denied any vision or systemic symptoms. Her ophthalmic history was noncontributory. The patient’s medical history was notable only for prostate carcinoma, which was treated with radiotherapy 12 years ago. On examination, her visual acuities were 20/25 OU. Slitlamp examination of the anterior segment revealed diffuse yellow-pink polypoidal papules affecting the inferior fornix and inferior palpebral conjunctiva of the left eye (Figure 1A). The upper palpebral conjunctiva in the left eye had a velvety yellow appearance (Figure 1B). The remainder of the examination of both eyes was unremarkable. Initial investigations, including a complete blood cell count, urinalysis, and measurement of inflammatory markers, kidney function, and prostate-specific antigen level, were within normal limits. Serum electrophoresis showed raised monoclonal IgM bands (7.25 g/L; reference range, 0.50-2.00 g/L) with a κ/λ light-chain ratio of 2.92 (reference range, 0.260-1.65). ### OUTPUT:

JAMA_FINAL232

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 89-year-old asymptomatic woman presented to a new eye care professional for a routine examination. Examination findings showed a large choroidal mass in the left eye suspicious for a malignant neoplasm. The patient’s ocular history showed a cataract surgical procedure, YAG capsulotomy, and subsequent repair of retinal detachment with scleral buckle and pneumatic retinopexy in the left eye approximately 30 years earlier. Ophthalmoscopic examination results of the left eye revealed a peripheral retinal atrophy from previous cryotherapy treatment. A large choroidal mass was observed in the inferotemporal region. The patient was referred for further evaluation of the mass, which was suspected to represent choroidal melanoma. Our examination findings showed a visual acuity of 20/20 OD and 20/60 OS, with intraocular pressures of 20 mm Hg OD and 16 mm Hg OS measured using a tonometer (Tono-pen; Reichert Inc). Ophthalmoscopy results of the right eye were normal. In the left eye, a 360° encircling band with overlying retinal atrophy was documented. There was a variably pigmented, abruptly elevated mass deep in the inferotemporal retina, measuring 12.0 mm in diameter (Figure, A) and without overlying drusen, orange pigment, or subretinal fluid. Ultrasonography results showed that the mass was dome shaped and echodense, with posterior shadowing (Figure, B); it measured 4.6 mm thick. Optical coherence tomographic imaging revealed an intact macula. ### OUTPUT:

Choroidal pseudomelanoma secondary to scleral buckle

['Retinal Disorders', 'Ophthalmology', 'Geriatrics', 'Ophthalmic Imaging', 'Choroidal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 89-year-old asymptomatic man presented to a new eye care professional for a routine examination. Examination findings showed a large choroidal mass in the left eye suspicious for a malignant neoplasm. The patient’s ocular history showed a cataract surgical procedure, YAG capsulotomy, and subsequent repair of retinal detachment with scleral buckle and pneumatic retinopexy in the left eye approximately 30 years earlier. Ophthalmoscopic examination results of the left eye revealed a peripheral retinal atrophy from previous cryotherapy treatment. A large choroidal mass was observed in the inferotemporal region. The patient was referred for further evaluation of the mass, which was suspected to represent choroidal melanoma. Our examination findings showed a visual acuity of 20/20 OD and 20/60 OS, with intraocular pressures of 20 mm Hg OD and 16 mm Hg OS measured using a tonometer (Tono-pen; Reichert Inc). Ophthalmoscopy results of the right eye were normal. In the left eye, a 360° encircling band with overlying retinal atrophy was documented. There was a variably pigmented, abruptly elevated mass deep in the inferotemporal retina, measuring 12.0 mm in diameter (Figure, A) and without overlying drusen, orange pigment, or subretinal fluid. Ultrasonography results showed that the mass was dome shaped and echodense, with posterior shadowing (Figure, B); it measured 4.6 mm thick. Optical coherence tomographic imaging revealed an intact macula. ### OUTPUT:

JAMA_FINAL233

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 39-year-old female patient with alveolar rhabdomyosarcoma and bone metastases presented in April 2020 with lower back pain, which was aggravated while standing and walking. She reported no known trauma, and no motor or sensory deficits were noted during clinical examination. She had no fever. After the initial sarcoma diagnosis in September 2018, the patient received 8 cycles of doxorubicin hydrochloride and ifosfamide along with regional hyperthermia, followed by good tumor response. The patient had a history of a pathological fracture of L4, which had been treated with radiotherapy and vertebroplasty in November 2019 and remained unchanged on imaging obtained in April 2020. The treatment regimen recently had been switched to gemcitabine hydrochloride and docetaxel in January 2020 following osseous progression during maintenance chemotherapy with trofosfamide, idarubicin hydrochloride, and etoposide. On restaging computed tomography, symmetrical enlargement of both psoas muscles was observed with intramuscular hypodensity (Figure, A). The patient reported lower back pain but no motor or sensory deficits. Further workup with magnetic resonance imaging (MRI) revealed extensive, nearly symmetrical swelling in both psoas muscles and sharply delineated, peripheral contrast enhancement of the fascia with strict horizontal bounds (Figure, B and C). ### OUTPUT:

Radiation recall myositis

['Radiation Oncology', 'Oncology', 'Sarcomas', 'Soft-Tissue Tumors']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 39-year-old male patient with alveolar rhabdomyosarcoma and bone metastases presented in April 2020 with lower back pain, which was aggravated while standing and walking. He reported no known trauma, and no motor or sensory deficits were noted during clinical examination. He had no fever. After the initial sarcoma diagnosis in September 2018, the patient received 8 cycles of doxorubicin hydrochloride and ifosfamide along with regional hyperthermia, followed by good tumor response. The patient had a history of a pathological fracture of L4, which had been treated with radiotherapy and vertebroplasty in November 2019 and remained unchanged on imaging obtained in April 2020. The treatment regimen recently had been switched to gemcitabine hydrochloride and docetaxel in January 2020 following osseous progression during maintenance chemotherapy with trofosfamide, idarubicin hydrochloride, and etoposide. On restaging computed tomography, symmetrical enlargement of both psoas muscles was observed with intramuscular hypodensity (Figure, A). The patient reported lower back pain but no motor or sensory deficits. Further workup with magnetic resonance imaging (MRI) revealed extensive, nearly symmetrical swelling in both psoas muscles and sharply delineated, peripheral contrast enhancement of the fascia with strict horizontal bounds (Figure, B and C). ### OUTPUT:

JAMA_FINAL234

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A patient in their late 70s with a history of Crohn disease, coronary artery disease, hypercholesterolemia, and transient ischemic attack presented with sudden, painless, left-sided vision loss. They denied headache, scalp tenderness, and jaw claudication. The erythrocyte sedimentation rate (ESR) was 103 mm/h and a magnetic resonance angiographic examination of the brain was negative for mass, infarction, and hemorrhage. Examination results of a right, superficial, temporal artery biopsy specimen showed chronic, nongranulomatous inflammation surrounding adventitial vessels and extensive subintimal fibrosis, without giant cells or segmental loss of the internal elastic lamina, which was interpreted as compatible with temporal arteritis. High-dose corticosteroid therapy was initiated (1 g methylprednisolone intravenously for 3 days followed by 60 mg/d of oral prednisone). A neuro-ophthalmologic examination performed 1 week later showed an unreactive left pupil with an obvious relative afferent pupillary defect. Optic nerve pallor concomitant with edema and a single flame-shaped hemorrhage at the 4-o’clock position on the disc margin was also observed. Two weeks later, persistent elevation of the ESR and C-reactive protein levels, despite continued oral prednisone therapy, prompted a review of the temporal artery biopsy findings. This disclosed abundant transmural deposits of amorphous eosinophilic acellular material that was congophilic and exhibited apple-green birefringence under polarized light, consistent with amyloid deposits (Figure). Immunohistochemical staining showed IgM and λ light chain restriction. ### OUTPUT:

Systemic amyloidosis in the setting of lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)

['Geriatrics', 'Hematology', 'Ophthalmology', 'Cardiology', 'Ischemic Heart Disease']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Case report: A patient in their late 70s with a history of Crohn disease, coronary artery disease, hypercholesterolemia, and transient ischemic attack presented with sudden, painless, left-sided vision loss. He denied headache, scalp tenderness, and jaw claudication. The erythrocyte sedimentation rate (ESR) was 103 mm/h and a magnetic resonance angiographic examination of the brain was negative for mass, infarction, and hemorrhage. Examination results of a right, superficial, temporal artery biopsy specimen showed chronic, nongranulomatous inflammation surrounding adventitial vessels and extensive subintimal fibrosis, without giant cells or segmental loss of the internal elastic lamina, which was interpreted as compatible with temporal arteritis. High-dose corticosteroid therapy was initiated (1 g methylprednisolone intravenously for 3 days followed by 60 mg/d of oral prednisone). A neuro-ophthalmologic examination performed 1 week later showed an unreactive left pupil with an obvious relative afferent pupillary defect. Optic nerve pallor concomitant with edema and a single flame-shaped hemorrhage at the 4-o’clock position on the disc margin was also observed. Two weeks later, persistent elevation of the ESR and C-reactive protein levels, despite continued oral prednisone therapy, prompted a review of the temporal artery biopsy findings. This disclosed abundant transmural deposits of amorphous eosinophilic acellular material that was congophilic and exhibited apple-green birefringence under polarized light, consistent with amyloid deposits (Figure). Immunohistochemical staining showed IgM and λ light chain restriction. ### OUTPUT:

JAMA_FINAL235

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 30s presented with a chronic history of slowly expanding asymptomatic papules on the dorsal hands since childhood, with more recent involvement of both forearms. She denied photosensitivity, arthritis, or muscle weakness. Examination revealed multiple discrete reddish-brown, well-defined, smooth 2- to 6-mm dome-shaped papules (Figure, A). There were no nail changes or mucous membrane involvement. ### OUTPUT:

Progressive mucinous histiocytosis

['Dermatology', 'Hematology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 30s presented with a chronic history of slowly expanding asymptomatic papules on the dorsal hands since childhood, with more recent involvement of both forearms. He denied photosensitivity, arthritis, or muscle weakness. Examination revealed multiple discrete reddish-brown, well-defined, smooth 2- to 6-mm dome-shaped papules (Figure, A). There were no nail changes or mucous membrane involvement. ### OUTPUT:

JAMA_FINAL236

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy, middle-aged patient presented with rapidly increasing shortness of breath despite empirical antibiotic treatment for presumed pneumonia. A computed tomographic image of the chest was notable for diffuse, ground-glass opacities. An infectious disease workup was unrevealing, and the patient was diagnosed with acute-on-chronic respiratory failure resulting from dermatomyositis-associated interstitial lung disease. Progressive hypoxia refractory to mechanical ventilation necessitated venovenous extracorporeal membrane oxygenation (VV ECMO) using the ProtekDuo dual-lumen cannula (LivaNova). In its standard configuration, deoxygenated blood is drained from the right atrium while oxygenated blood is ejected into the main pulmonary artery, and the device serves as both a right ventricular support and an ECMO (RVS-ECMO) cannula. End-stage lung disease was established and, as part of a lung transplant evaluation, the patient underwent catheterization of the left side of the heart and coronary angiography. The left coronary artery angiogram revealed mild luminal irregularities. The right coronary artery (RCA) angiogram is shown in Figure 1 and Video 1. ### OUTPUT:

Right coronary artery compression by the right ventricular angulation of the RVS-ECMO cannula

['Cardiology', 'Critical Care Medicine', 'Respiratory Failure and Ventilation']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy, middle-aged patient presented with rapidly increasing shortness of breath despite empirical antibiotic treatment for presumed pneumonia. A computed tomographic image of the chest was notable for diffuse, ground-glass opacities. An infectious disease workup was unrevealing, and the patient was diagnosed with acute-on-chronic respiratory failure resulting from dermatomyositis-associated interstitial lung disease. Progressive hypoxia refractory to mechanical ventilation necessitated venovenous extracorporeal membrane oxygenation (VV ECMO) using the ProtekDuo dual-lumen cannula (LivaNova). In its standard configuration, deoxygenated blood is drained from the right atrium while oxygenated blood is ejected into the main pulmonary artery, and the device serves as both a right ventricular support and an ECMO (RVS-ECMO) cannula. End-stage lung disease was established and, as part of a lung transplant evaluation, the patient underwent catheterization of the left side of the heart and coronary angiography. The left coronary artery angiogram revealed mild luminal irregularities. The right coronary artery (RCA) angiogram is shown in Figure 1 and Video 1. ### OUTPUT:

JAMA_FINAL237

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A middle-aged woman presented with chest pain, elevated troponin-T of 1037 ng/L (normal <14 ng/L; to convert to micrograms per liter, multiply by 1), and anterior T-wave inversion on electrocardiography. She was a smoker with hypertension and kidney dysfunction, with a history of left-sided paresthesia. Coronary angiography demonstrated unobstructed coronary arteries. Cardiovascular magnetic resonance (CMR) imaging revealed subendocardial midinferolateral late gadolinium enhancement with corresponding hypokinesis consistent with a partial-thickness myocardial infarction. Prolonged Holter monitoring showed no evidence of atrial fibrillation. Two years later, she had a similar presentation consistent with a non–ST-elevation myocardial infarction. Repeated coronary angiography again demonstrated unobstructed coronary arteries. The CMR revealed the same midinferolateral late gadolinium enhancement as at the initial examination (Figure, A) but with focal enhancement on T2 short tau inversion recovery sequences (Figure, B), with increased T1 and T2 values suggestive of associated edema from an acute infarction in the same territory. A mobile interatrial septum was noted on 4-chamber cine imaging. A transthoracic echocardiogram bubble study demonstrated color flow at rest across the interatrial septum and a large shunt on Valsalva maneuver consistent with a grade 3 patent foramen ovale (PFO) (Video). Coincidentally, a brain MR scan to investigate the recurrent paresthesia revealed bilateral white matter lesions thought to be secondary to small-vessel disease greater in number than expected for the patient’s age, raising suspicion for microemboli. ### OUTPUT:

Paradoxical embolism through PFO causing recurrent systemic embolism

['Acute Coronary Syndromes', 'Congenital Defects', 'Cardiology', 'Cerebrovascular Disease', 'Neurology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A middle-aged man presented with chest pain, elevated troponin-T of 1037 ng/L (normal <14 ng/L; to convert to micrograms per liter, multiply by 1), and anterior T-wave inversion on electrocardiography. He was a smoker with hypertension and kidney dysfunction, with a history of left-sided paresthesia. Coronary angiography demonstrated unobstructed coronary arteries. Cardiovascular magnetic resonance (CMR) imaging revealed subendocardial midinferolateral late gadolinium enhancement with corresponding hypokinesis consistent with a partial-thickness myocardial infarction. Prolonged Holter monitoring showed no evidence of atrial fibrillation. Two years later, he had a similar presentation consistent with a non–ST-elevation myocardial infarction. Repeated coronary angiography again demonstrated unobstructed coronary arteries. The CMR revealed the same midinferolateral late gadolinium enhancement as at the initial examination (Figure, A) but with focal enhancement on T2 short tau inversion recovery sequences (Figure, B), with increased T1 and T2 values suggestive of associated edema from an acute infarction in the same territory. A mobile interatrial septum was noted on 4-chamber cine imaging. A transthoracic echocardiogram bubble study demonstrated color flow at rest across the interatrial septum and a large shunt on Valsalva maneuver consistent with a grade 3 patent foramen ovale (PFO) (Video). Coincidentally, a brain MR scan to investigate the recurrent paresthesia revealed bilateral white matter lesions thought to be secondary to small-vessel disease greater in number than expected for the patient’s age, raising suspicion for microemboli. ### OUTPUT:

JAMA_FINAL238

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old man presented with several weeks of intermittent headache that had progressed to severe, persistent headache with right eye pain. He had hypertension, hyperlipidemia, diabetes, and atrial fibrillation. He denied tobacco, alcohol, or drug use. A neurological examination was notable for disorientation to the month, deficits in short-term memory, and an upward drift of the left arm. Cranial nerve, sensory, coordination, and deep tendon reflex examinations were normal. He walked with a slightly wide but steady gait. His serum red and white blood cell counts, coagulation profile, and electrolyte levels were within normal limits. Blood cultures had negative results. A 24-hour electroencephalogram showed right hemispheric slowing and multiple right centroparietal seizures of 1 minute each, without noticeable clinical correlates. A magnetic resonance image (MRI) of the brain was remarkable for a large T2-hyperintense lesion in the right temporoparietal region, with an increased diffusion-weighted imaging (DWI) signal (low apparent diffusion coefficient), a low signal on susceptibility-weighted imaging, increased T1 signal intensity in and around the lesion, and a contrast-enhancing rim with leptomeningeal enhancement (Figure 1). A smaller satellite lesion with a similar MRI profile was noted inferiorly in the right anterior temporal lobe. A computed tomography scan of the chest, abdomen, and pelvis did not show any metastatic disease. A cerebrospinal fluid (CSF) profile showed a normal red blood cell count and protein and glucose levels and a mildly elevated white blood cell count of 11 cells/μL (to convert to cells × 109/L, multiply by 0.001). The fluid was absent oligoclonal bands and had negative bacterial and fungal culture results, a meningitis-encephalitis polymerase chain reaction panel, and a paraneoplastic panel. Cytology and flow cytometry had negative results. The patient then underwent surgical biopsy of the temporoparietal lesion. ### OUTPUT:

Cerebral amyloid angiopathy–related inflammation

['Headache', 'Neurology', 'Neuroimaging', 'Radiology', 'Dementia and Cognitive Impairment']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old woman presented with several weeks of intermittent headache that had progressed to severe, persistent headache with right eye pain. She had hypertension, hyperlipidemia, diabetes, and atrial fibrillation. She denied tobacco, alcohol, or drug use. A neurological examination was notable for disorientation to the month, deficits in short-term memory, and an upward drift of the left arm. Cranial nerve, sensory, coordination, and deep tendon reflex examinations were normal. She walked with a slightly wide but steady gait. Her serum red and white blood cell counts, coagulation profile, and electrolyte levels were within normal limits. Blood cultures had negative results. A 24-hour electroencephalogram showed right hemispheric slowing and multiple right centroparietal seizures of 1 minute each, without noticeable clinical correlates. A magnetic resonance image (MRI) of the brain was remarkable for a large T2-hyperintense lesion in the right temporoparietal region, with an increased diffusion-weighted imaging (DWI) signal (low apparent diffusion coefficient), a low signal on susceptibility-weighted imaging, increased T1 signal intensity in and around the lesion, and a contrast-enhancing rim with leptomeningeal enhancement (Figure 1). A smaller satellite lesion with a similar MRI profile was noted inferiorly in the right anterior temporal lobe. A computed tomography scan of the chest, abdomen, and pelvis did not show any metastatic disease. A cerebrospinal fluid (CSF) profile showed a normal red blood cell count and protein and glucose levels and a mildly elevated white blood cell count of 11 cells/μL (to convert to cells × 109/L, multiply by 0.001). The fluid was absent oligoclonal bands and had negative bacterial and fungal culture results, a meningitis-encephalitis polymerase chain reaction panel, and a paraneoplastic panel. Cytology and flow cytometry had negative results. The patient then underwent surgical biopsy of the temporoparietal lesion. ### OUTPUT:

JAMA_FINAL239

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 40-year-old man with refractory glaucoma was referred for decreased vision in the right eye after an aqueous shunting surgical procedure 3 weeks prior. The surgical procedure was a 2-staged Baerveldt implantation after which he developed fluctuating but progressive visual decline. The patient’s ocular history was significant for Sturge-Weber syndrome with bilateral cutaneous port-wine stains, secondary glaucoma in the right eye, and an irregular globe with a white cataract and chronic retinal detachment (RD) in the left eye. At presentation, visual acuity was hand motion OD and a long-standing history of no light perception OS. Intraocular pressures by Goldmann applanation tonometry were 16 mm Hg OD and 28 mm Hg OS. Anterior segment examination of the right eye revealed a properly positioned plate and tube, and dilated fundus examination revealed a red glow of the fundus with shifting subretinal fluid and RD extending from the 2- to 11-o’clock position (Figure 1A). B-scan ultrasonography of the right eye confirmed the RD and demonstrated homogeneous diffuse choroidal thickening (Figure 1B). ### OUTPUT:

Diffuse choroidal hemangioma with exudative retinal detachments

['Ophthalmology', 'Choroidal Disorders', 'Retinal Disorders', 'Glaucoma']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 40-year-old woman with refractory glaucoma was referred for decreased vision in the right eye after an aqueous shunting surgical procedure 3 weeks prior. The surgical procedure was a 2-staged Baerveldt implantation after which she developed fluctuating but progressive visual decline. The patient’s ocular history was significant for Sturge-Weber syndrome with bilateral cutaneous port-wine stains, secondary glaucoma in the right eye, and an irregular globe with a white cataract and chronic retinal detachment (RD) in the left eye. At presentation, visual acuity was hand motion OD and a long-standing history of no light perception OS. Intraocular pressures by Goldmann applanation tonometry were 16 mm Hg OD and 28 mm Hg OS. Anterior segment examination of the right eye revealed a properly positioned plate and tube, and dilated fundus examination revealed a red glow of the fundus with shifting subretinal fluid and RD extending from the 2- to 11-o’clock position (Figure 1A). B-scan ultrasonography of the right eye confirmed the RD and demonstrated homogeneous diffuse choroidal thickening (Figure 1B). ### OUTPUT:

JAMA_FINAL240

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 49-year-old African American man who was hospitalized with hypervolemia due to supraventricular tachycardia presented with acute unilateral painless vision loss. His active medical problems included atrial flutter on anticoagulation, antisynthetase syndrome (which was diagnosed based on the presence of autoantibodies against aminoacyl-tRNA synthetase), fever with negative infectious workup results, and interstitial lung disease that was managed with azathioprine. Two weeks before the onset of sudden vision loss, the patient developed a rapidly evolving purpuric rash on his hands and feet that progressed to digital ischemia (Figure 1A). He was treated with intravenous methylprednisolone, which was completed 3 days before the onset of loss of vision and transitioned to treatment with azathioprine, 150 mg, and prednisone, 80 mg, that he was taking at the time of his vision loss. ### OUTPUT:

Frosted branch angiitis due to retinal vasculitis that was associated with antisynthetase syndrome

['Dermatology', 'Rheumatology', 'Ophthalmology', 'Retinal Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 49-year-old African American woman who was hospitalized with hypervolemia due to supraventricular tachycardia presented with acute unilateral painless vision loss. Her active medical problems included atrial flutter on anticoagulation, antisynthetase syndrome (which was diagnosed based on the presence of autoantibodies against aminoacyl-tRNA synthetase), fever with negative infectious workup results, and interstitial lung disease that was managed with azathioprine. Two weeks before the onset of sudden vision loss, the patient developed a rapidly evolving purpuric rash on her hands and feet that progressed to digital ischemia (Figure 1A). She was treated with intravenous methylprednisolone, which was completed 3 days before the onset of loss of vision and transitioned to treatment with azathioprine, 150 mg, and prednisone, 80 mg, that she was taking at the time of her vision loss. ### OUTPUT:

JAMA_FINAL241

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s presented to the clinic with a several-day history of nontender, nonitchy purpuric rash on his scalp. The patient denied using any over-the-counter or prescription topicals at the affected sites before the onset of the eruption except for petroleum jelly. His medical history was significant for chronic lymphocytic leukemia (CLL) and allergic contact dermatitis. The patient reported being started on ibrutinib and allopurinol therapy 6 weeks prior to the rash onset for treatment of CLL. Physical examination revealed multiple purpuric, nonblanchable macules and patches on the frontal, vertex, temporal, and parietal scalp (Figure, A). A punch biopsy specimen from the scalp was obtained for histopathologic analysis (Figure, B). ### OUTPUT:

Ibrutinib-induced toxic effects

['Dermatology', 'Cutaneous Drug Reactions', 'Targeted and Immune Therapy', 'Oncology', 'Hematologic Cancer']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s presented to the clinic with a several-day history of nontender, nonitchy purpuric rash on her scalp. The patient denied using any over-the-counter or prescription topicals at the affected sites before the onset of the eruption except for petroleum jelly. Her medical history was significant for chronic lymphocytic leukemia (CLL) and allergic contact dermatitis. The patient reported being started on ibrutinib and allopurinol therapy 6 weeks prior to the rash onset for treatment of CLL. Physical examination revealed multiple purpuric, nonblanchable macules and patches on the frontal, vertex, temporal, and parietal scalp (Figure, A). A punch biopsy specimen from the scalp was obtained for histopathologic analysis (Figure, B). ### OUTPUT:

JAMA_FINAL242

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 82-year-old man with an ocular history significant for bilateral nuclear sclerotic cataracts presented to the Cornea Service at Bascom Palmer Eye Institute, Miami, Florida, with a history of blurred vision in the right eye after phacoemulsification cataract extraction 8 weeks earlier. Current ophthalmic medications included topical prednisolone acetate, 1%, in the right eye 6 times per day. The patient reported no improvement with the treatment. On examination, his best-corrected visual acuity was 20/80 OD and 20/20 OS. Pupils were reactive without relative afferent pupillary defect, and intraocular pressures were 18 mm Hg in the right eye and 11 mm Hg in the left eye. A slitlamp biomicroscopic examination of the right eye revealed grade 2 to 3 diffuse central corneal edema and folds (Figure 1). The anterior chamber was deep and the posterior chamber intraocular lens was in good position within the capsular bag. Although the view to the posterior pole of the right eye was hazy owing to corneal edema, dilated fundus examination findings were unremarkable. Examination of the left eye revealed a few guttate. The central corneal thickness by ultrasound pachymetry was 957 μm in the right eye and 547 μm in the left eye. ### OUTPUT:

Corneal edema after cataract surgery secondary to intraoperative Descemet membrane detachment (Figure 2)

['Cornea', 'Cataract and Other Lens Disorders', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 82-year-old woman with an ocular history significant for bilateral nuclear sclerotic cataracts presented to the Cornea Service at Bascom Palmer Eye Institute, Miami, Florida, with a history of blurred vision in the right eye after phacoemulsification cataract extraction 8 weeks earlier. Current ophthalmic medications included topical prednisolone acetate, 1%, in the right eye 6 times per day. The patient reported no improvement with the treatment. On examination, her best-corrected visual acuity was 20/80 OD and 20/20 OS. Pupils were reactive without relative afferent pupillary defect, and intraocular pressures were 18 mm Hg in the right eye and 11 mm Hg in the left eye. A slitlamp biomicroscopic examination of the right eye revealed grade 2 to 3 diffuse central corneal edema and folds (Figure 1). The anterior chamber was deep and the posterior chamber intraocular lens was in good position within the capsular bag. Although the view to the posterior pole of the right eye was hazy owing to corneal edema, dilated fundus examination findings were unremarkable. Examination of the left eye revealed a few guttate. The central corneal thickness by ultrasound pachymetry was 957 μm in the right eye and 547 μm in the left eye. ### OUTPUT:

JAMA_FINAL243

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 17-month-old boy was referred to pediatric dermatology for evaluation of a slow-growing, nontender plaque on the lower back. The child's mother reported that, on discovery, the plaque was initially 1 × 1 cm and had since grown in size with the child. She was uncertain if the plaque was present at birth. The patient’s medical history was significant for dermal melanocytosis of the right hip and mid back, increased head circumference (97th percentile), and expressive language delay. There was no family history of congenital birthmarks or neurofibromatosis type 1 or 2. Physical examination revealed a well-appearing boy with normal vital signs and Fitzpatrick type III skin type. On the left lower back, there was a 15 × 5-cm indurated skin-colored to yellow, firm, multinodular plaque with hypertrichosis, extending from the midline to the left lower flank (Figure, A). There were additional blue-gray patches on the back and right hip, as well as a small café au lait macule on the right lower back. Limited neurologic examination was within normal limits. A 4-mm punch biopsy was performed for further diagnostic evaluation (Figure, B-D). ### OUTPUT:

Neurocristic hamartoma

['Pediatrics', 'Dermatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 17-month-old girl was referred to pediatric dermatology for evaluation of a slow-growing, nontender plaque on the lower back. The child's mother reported that, on discovery, the plaque was initially 1 × 1 cm and had since grown in size with the child. She was uncertain if the plaque was present at birth. The patient’s medical history was significant for dermal melanocytosis of the right hip and mid back, increased head circumference (97th percentile), and expressive language delay. There was no family history of congenital birthmarks or neurofibromatosis type 1 or 2. Physical examination revealed a well-appearing girl with normal vital signs and Fitzpatrick type III skin type. On the left lower back, there was a 15 × 5-cm indurated skin-colored to yellow, firm, multinodular plaque with hypertrichosis, extending from the midline to the left lower flank (Figure, A). There were additional blue-gray patches on the back and right hip, as well as a small café au lait macule on the right lower back. Limited neurologic examination was within normal limits. A 4-mm punch biopsy was performed for further diagnostic evaluation (Figure, B-D). ### OUTPUT:

JAMA_FINAL244

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 9-year-old boy was referred to the pediatric otolaryngology clinic with a 3-month history of a left-sided neck mass. The mass had been slowly enlarging and he had been experiencing mild intermittent pain, but no additional symptoms were reported. His medical history was significant for several episodes of upper respiratory infection during the previous winter season, and he previously had an adenotonsillectomy several years prior and bilateral ear tubes placed 1 year before presentation. Physical examination showed a mildly tender, nonmobile, left parotid mass near the angle of the mandible with no overlying skin changes or drainage around the mass. There was no lymphadenopathy or other lesions noted in the neck area, and cranial nerve VII was fully intact. Ultrasonography results of the neck showed a left 1.5-cm preauricular nodular mass with internal and marginal vascularity. A neck magnetic resonance imaging study without contrast performed at an outside institution revealed the 1.5-cm heterogeneous intraparotid nodule that was predominantly isotense to glandular tissue on T1 images with vague hypointensity of a small irregular central region, as well as vague hyperintensity on T2 images. He subsequently underwent fine needle aspiration biopsy to assess the lesion, which demonstrated benign-appearing salivary gland tissue and clusters of myoepithelial cells. The mass was continuing to enlarge, and the patient’s pain was increasing in that area, so the decision was made to perform left superficial parotidectomy with preservation of the facial nerve. Intraoperatively, the left parotid mass was noted to be just below the lower branches of the facial nerve. The excised parotid mass was sent to the pathology department for analysis. Gross examination of the specimen demonstrated a 1.6 × 1.5 × 1.1–cm tan-white, well-circumscribed lesion that was partially surrounded by salivary gland parenchyma (Figure, A). Histologic examination of the nodule was performed (Figure, B and C). ### OUTPUT:

Sclerosing polycystic adenoma

['Pediatrics', 'Otolaryngology', 'Salivary Gland Disorders', 'Dental Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 9-year-old girl was referred to the pediatric otolaryngology clinic with a 3-month history of a left-sided neck mass. The mass had been slowly enlarging and she had been experiencing mild intermittent pain, but no additional symptoms were reported. Her medical history was significant for several episodes of upper respiratory infection during the previous winter season, and she previously had an adenotonsillectomy several years prior and bilateral ear tubes placed 1 year before presentation. Physical examination showed a mildly tender, nonmobile, left parotid mass near the angle of the mandible with no overlying skin changes or drainage around the mass. There was no lymphadenopathy or other lesions noted in the neck area, and cranial nerve VII was fully intact. Ultrasonography results of the neck showed a left 1.5-cm preauricular nodular mass with internal and marginal vascularity. A neck magnetic resonance imaging study without contrast performed at an outside institution revealed the 1.5-cm heterogeneous intraparotid nodule that was predominantly isotense to glandular tissue on T1 images with vague hypointensity of a small irregular central region, as well as vague hyperintensity on T2 images. She subsequently underwent fine needle aspiration biopsy to assess the lesion, which demonstrated benign-appearing salivary gland tissue and clusters of myoepithelial cells. The mass was continuing to enlarge, and the patient’s pain was increasing in that area, so the decision was made to perform left superficial parotidectomy with preservation of the facial nerve. Intraoperatively, the left parotid mass was noted to be just below the lower branches of the facial nerve. The excised parotid mass was sent to the pathology department for analysis. Gross examination of the specimen demonstrated a 1.6 × 1.5 × 1.1–cm tan-white, well-circumscribed lesion that was partially surrounded by salivary gland parenchyma (Figure, A). Histologic examination of the nodule was performed (Figure, B and C). ### OUTPUT:

JAMA_FINAL245

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old woman with non-Hodgkin lymphoma receiving maintenance obinutuzumab (anti-CD20 monoclonal antibody) infusions underwent uneventful pars plana vitrectomy of the right eye for vitreomacular traction. Diluted triamcinolone acetonide (TA) was used to stain the posterior hyaloid. After removal of 25-gauge trocar cannulas, subconjunctival TA and ceftazidime was injected. Owing to cystoid changes in the central macula, a short-acting gas tamponade with sulfur hexafluoride was used to tamponade any cystoid abnormalities that may have been unroofed. Despite unremarkable postoperative day 1 (POD1) examination findings, the patient presented on postoperative week 3 with a painless central scotoma and worsening floaters. Her visual acuity was 20/400 OD and intraocular pressure was normal. There was no external hyperemia or chemosis, and the anterior chamber was deep and quiet with no cells or flare. On dilated fundus examination, there were 15 to 20 cells per high-power field (using a 1 × 1-mm2 high-intensity incidental slit beam) and a white macular lesion with disc edema and scattered intraretinal and peripapillary hemorrhages and mixed venous and arterial sheathing. Optical coherence tomography of the macula showed atrophy, full-thickness hyperreflectivity, and a residual epiretinal membrane (Figure). ### OUTPUT:

Cytomegalovirus retinitis and papillitis

['Infectious Diseases', 'Ophthalmology', 'Retinal Disorders', 'Macular Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old man with non-Hodgkin lymphoma receiving maintenance obinutuzumab (anti-CD20 monoclonal antibody) infusions underwent uneventful pars plana vitrectomy of the right eye for vitreomacular traction. Diluted triamcinolone acetonide (TA) was used to stain the posterior hyaloid. After removal of 25-gauge trocar cannulas, subconjunctival TA and ceftazidime was injected. Owing to cystoid changes in the central macula, a short-acting gas tamponade with sulfur hexafluoride was used to tamponade any cystoid abnormalities that may have been unroofed. Despite unremarkable postoperative day 1 (POD1) examination findings, the patient presented on postoperative week 3 with a painless central scotoma and worsening floaters. His visual acuity was 20/400 OD and intraocular pressure was normal. There was no external hyperemia or chemosis, and the anterior chamber was deep and quiet with no cells or flare. On dilated fundus examination, there were 15 to 20 cells per high-power field (using a 1 × 1-mm2 high-intensity incidental slit beam) and a white macular lesion with disc edema and scattered intraretinal and peripapillary hemorrhages and mixed venous and arterial sheathing. Optical coherence tomography of the macula showed atrophy, full-thickness hyperreflectivity, and a residual epiretinal membrane (Figure). ### OUTPUT:

JAMA_FINAL246

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A girl younger than 2 years presented with a 1-year history of slightly pruritic lesions involving her face. She was born after an uncomplicated pregnancy and delivery, and her growth and development were appropriate for her age. No associated symptoms such as fever, anorexia, or weight loss were noted. Physical examination revealed multiple skin-colored and erythematous follicular papules, 1 to 2 mm in diameter, distributed in a segmental pattern on the right side of the forehead, as well as the dorsum and tip of the nose. A small, excoriated plaque was also noted on the right malar area (Figure 1A). No mucosal lesions were present, and the rest of the physical examination findings were unremarkable. A complete hematological and biochemical survey, including blood cell count, liver and renal function tests, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, disclosed no abnormalities. Two skin punch biopsies were taken from the forehead and nose. Representative histopathological features are shown in Figure 1B and C. ### OUTPUT:

Idiopathic follicular mucinosis

['Dermatology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A boy younger than 2 years presented with a 1-year history of slightly pruritic lesions involving his face. He was born after an uncomplicated pregnancy and delivery, and his growth and development were appropriate for his age. No associated symptoms such as fever, anorexia, or weight loss were noted. Physical examination revealed multiple skin-colored and erythematous follicular papules, 1 to 2 mm in diameter, distributed in a segmental pattern on the right side of the forehead, as well as the dorsum and tip of the nose. A small, excoriated plaque was also noted on the right malar area (Figure 1A). No mucosal lesions were present, and the rest of the physical examination findings were unremarkable. A complete hematological and biochemical survey, including blood cell count, liver and renal function tests, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, disclosed no abnormalities. Two skin punch biopsies were taken from the forehead and nose. Representative histopathological features are shown in Figure 1B and C. ### OUTPUT:

JAMA_FINAL247

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old woman with a history of hypertension and type 2 diabetes for more than 15 years was referred for proliferative diabetic retinopathy management. Her chief complaint was acute onset of blurry vision in the right eye. She described intermittent foggy vision and the appearance of “a hair moving across the vision of her right eye” for the past few weeks. Her most recent hemoglobin A1c level was 8.3%, and 2 months prior to her visit, she had restarted diabetes medications. Her medications included metformin and glimepiride. Her corrected visual acuity was 20/20 OU. Her pupil, color vision, and anterior segment examinations had normal results bilaterally. A posterior segment examination of the right eye showed mild temporal elevation of the optic disc with blurred margins, mild peripapillary hemorrhages, a small amount of preretinal hemorrhage, and small-caliber branching vessels at the temporal disc with no fibrosis (Figure 1A). The left eye showed a normal optic disc, a cup-disc ratio of 0.1, and some microaneurysms at the macula. There were a few scattered dot-blot hemorrhages bilaterally. Fluorescein angiography of the right eye showed mild leakage from the abnormal vessels at the temporal optic disc (Figure 1B). ### OUTPUT:

Diabetic papillopathy

['Diabetes', 'Retinal Disorders', 'Diabetes and Endocrinology', 'Diabetic Retinopathy', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 47-year-old man with a history of hypertension and type 2 diabetes for more than 15 years was referred for proliferative diabetic retinopathy management. His chief complaint was acute onset of blurry vision in the right eye. He described intermittent foggy vision and the appearance of “a hair moving across the vision of his right eye” for the past few weeks. His most recent hemoglobin A1c level was 8.3%, and 2 months prior to his visit, he had restarted diabetes medications. His medications included metformin and glimepiride. His corrected visual acuity was 20/20 OU. His pupil, color vision, and anterior segment examinations had normal results bilaterally. A posterior segment examination of the right eye showed mild temporal elevation of the optic disc with blurred margins, mild peripapillary hemorrhages, a small amount of preretinal hemorrhage, and small-caliber branching vessels at the temporal disc with no fibrosis (Figure 1A). The left eye showed a normal optic disc, a cup-disc ratio of 0.1, and some microaneurysms at the macula. There were a few scattered dot-blot hemorrhages bilaterally. Fluorescein angiography of the right eye showed mild leakage from the abnormal vessels at the temporal optic disc (Figure 1B). ### OUTPUT:

JAMA_FINAL248

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 29-year-old man presented with a 2-month history of rapidly growing, widespread, asymptomatic skin nodules all over his body. He denied having fever, chills, fatigue, night sweats, or weight loss. He had no history of malignant neoplasm or chemical exposure. Physical examination findings demonstrated numerous erythematous, indurated nodules involving the surface of his head, neck, torso, and extremities, without ulceration or scarring (Figure, A and B). Findings of systemic reviews were unremarkable, and there was no lymphadenopathy or peripheral nerve enlargement. Complete blood cell count with differential results were normal (white blood cell count, 6060/μL, normal range, 4500-10 000/μL; absolute neutrophils, 3070/μL, normal range, 1800-8300/μL [to convert cell counts to ×109/L, multiply by 0.001]). Serum lactate dehydrogenase level was elevated (279 U/L, normal range, 100-240 U/L [to convert to μkat/L, multiply by 0.0167]). Biopsies from skin nodules (Figure, C) and bone marrow were obtained. ### OUTPUT:

Aleukemic cutaneous myeloid sarcoma

['Dermatology', 'Oncology', 'Sarcomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 29-year-old woman presented with a 2-month history of rapidly growing, widespread, asymptomatic skin nodules all over her body. She denied having fever, chills, fatigue, night sweats, or weight loss. She had no history of malignant neoplasm or chemical exposure. Physical examination findings demonstrated numerous erythematous, indurated nodules involving the surface of her head, neck, torso, and extremities, without ulceration or scarring (Figure, A and B). Findings of systemic reviews were unremarkable, and there was no lymphadenopathy or peripheral nerve enlargement. Complete blood cell count with differential results were normal (white blood cell count, 6060/μL, normal range, 4500-10 000/μL; absolute neutrophils, 3070/μL, normal range, 1800-8300/μL [to convert cell counts to ×109/L, multiply by 0.001]). Serum lactate dehydrogenase level was elevated (279 U/L, normal range, 100-240 U/L [to convert to μkat/L, multiply by 0.0167]). Biopsies from skin nodules (Figure, C) and bone marrow were obtained. ### OUTPUT:

JAMA_FINAL249

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A teenaged girl presented with recurrent episodes of chest and neck palpitations accompanied by headaches for 3 years, with sudden onset and offset. She had no specific medical or family history and had no treatment. A resting electrocardiogram (ECG) while symptomatic showed a wide QRS complex rhythm at a rate of 81 beats per minute (Figure 1A). After a short walk, symptoms disappeared and another ECG was recorded (Figure 1B). Physical examination and transthoracic echocardiography results were normal. ### OUTPUT:

Spontaneous abnormal automaticity from a left lateral accessory pathway

['Rhythm Disorders', 'Cardiology', 'Adolescent Medicine', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A teenaged boy presented with recurrent episodes of chest and neck palpitations accompanied by headaches for 3 years, with sudden onset and offset. He had no specific medical or family history and had no treatment. A resting electrocardiogram (ECG) while symptomatic showed a wide QRS complex rhythm at a rate of 81 beats per minute (Figure 1A). After a short walk, symptoms disappeared and another ECG was recorded (Figure 1B). Physical examination and transthoracic echocardiography results were normal. ### OUTPUT:

JAMA_FINAL250

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A male in his 60s presented with a hoarse and weak voice. He has a history of follicular lymphoma with multiple relapses treated with an allogeneic stem cell transplant complicated by graft-vs-host disease and was treated with sirolimus and steroids. Flexible fiber-optic nasolaryngoscopy demonstrated symmetric nodular projections with edema along the whole length of both true vocal folds (Figure 1A). The patient underwent microdirect laryngoscopy and biopsy of the vocal fold lesions. The histopathologic image is shown in Figure 1B. ### OUTPUT:

Rhabdomyoma

['Laryngology', 'Otolaryngology', 'Allergy and Clinical Immunology', 'Stem Cell Transplantation', 'Hematology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A female in her 60s presented with a hoarse and weak voice. She has a history of follicular lymphoma with multiple relapses treated with an allogeneic stem cell transplant complicated by graft-vs-host disease and was treated with sirolimus and steroids. Flexible fiber-optic nasolaryngoscopy demonstrated symmetric nodular projections with edema along the whole length of both true vocal folds (Figure 1A). The patient underwent microdirect laryngoscopy and biopsy of the vocal fold lesions. The histopathologic image is shown in Figure 1B. ### OUTPUT:

JAMA_FINAL251

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old woman presented to the clinic with intermittent pain inside her mouth and a progressive decline in oral aperture that had developed over the prior year. She described a burning sensation inside her mouth that worsened with using mouthwash and eating spicy foods. She had no history of cigarette smoking or use of chewing tobacco but had chewed areca nuts for many years while living in India. Currently, she reported chewing areca nuts daily to weekly. Physical examination revealed white-tan plaques on the oral mucosa and thickened buccal mucosae bilaterally (Figure). Her lips and perioral skin appeared healthy, and the interincisal distance, defined as the distance between the tips of the frontal incisors when the mouth is opened as wide as possible, was approximately 25 mm (reference, >35 mm). Examination of a biopsy sample of the lower left labial mucosa revealed subepithelial fibrosis with stromal hyalinization, without epithelial dysplasia or inflammatory changes. ### OUTPUT:

Oral submucous fibrosis

['Tobacco and e-Cigarettes', 'Dental Medicine', 'Pain Medicine', 'Pathology and Laboratory Medicine', 'Lifestyle Behaviors']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 63-year-old man presented to the clinic with intermittent pain inside his mouth and a progressive decline in oral aperture that had developed over the prior year. He described a burning sensation inside his mouth that worsened with using mouthwash and eating spicy foods. He had no history of cigarette smoking or use of chewing tobacco but had chewed areca nuts for many years while living in India. Currently, he reported chewing areca nuts daily to weekly. Physical examination revealed white-tan plaques on the oral mucosa and thickened buccal mucosae bilaterally (Figure). His lips and perioral skin appeared healthy, and the interincisal distance, defined as the distance between the tips of the frontal incisors when the mouth is opened as wide as possible, was approximately 25 mm (reference, >35 mm). Examination of a biopsy sample of the lower left labial mucosa revealed subepithelial fibrosis with stromal hyalinization, without epithelial dysplasia or inflammatory changes. ### OUTPUT:

JAMA_FINAL252

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old girl presented to the dermatology clinic in autumn with an asymptomatic rash on her arms, face, and legs of a 3-week duration. She was otherwise healthy with a history of having seasonal allergies and taking cetirizine. She had negative results from the review of systems and denied any recent illnesses, vaccinations, or new medications. Physical examination was notable for erythematous annular thin plaques without surface change on her right cheek (Figure 1A), an erythematous, edematous plaque on her nose (Figure 1A), and erythematous, edematous, annular papules and plaques on her arms, hands, and thighs (Figure 1B). A biopsy specimen was obtained from the right arm for histopathologic analysis. ### OUTPUT:

Cutaneous lupus erythematosus

['Dermatology', 'Rheumatology', 'Connective Tissue Disease of the Skin', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old boy presented to the dermatology clinic in autumn with an asymptomatic rash on his arms, face, and legs of a 3-week duration. He was otherwise healthy with a history of having seasonal allergies and taking cetirizine. He had negative results from the review of systems and denied any recent illnesses, vaccinations, or new medications. Physical examination was notable for erythematous annular thin plaques without surface change on his right cheek (Figure 1A), an erythematous, edematous plaque on his nose (Figure 1A), and erythematous, edematous, annular papules and plaques on his arms, hands, and thighs (Figure 1B). A biopsy specimen was obtained from the right arm for histopathologic analysis. ### OUTPUT:

JAMA_FINAL253

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A Black woman in her early 70s with a history of coronary artery disease after coronary artery bypass operations, hypertension, and colon polyps presented to oculoplastic surgery with 1 week of progressive right-sided proptosis and headache, described as severe pain radiating to the back of her head. This was associated with right eyelid ptosis and blurry vision. Prior to presentation, an outside ophthalmologist treated her with 1 week of oral prednisone, 20 mg/d, for presumed orbital inflammation with no improvement. She denied additional symptoms. Notably, she described headache and sudden vision loss in the right eye after coronary artery bypass grafting 1 year ago for several days before spontaneous improvement with incomplete resolution. Personal and family histories were negative for malignant neoplasm and autoimmune disease. Examination revealed right-sided uncorrected Snellen visual acuity of 20/60 associated with restricted supraduction, abduction, and infraduction. Pupils were equal in size without a relative afferent pupillary defect, and intraocular pressures were 10 mm Hg OD and 11 mm Hg OS. Visual fields had temporal restriction to confrontation of the right eye. Vision, motility, and visual fields were normal on the left. Pertinent findings included right-sided proptosis of 2 mm, cranial nerve V1 and V2 hypoesthesia, eyelid ptosis with a margin to reflex distance 1 of 0 mm, optic disc pallor, and vessel attenuation. Outside magnetic resonance imaging (MRI) demonstrated an infiltrative mass involving right greater than left orbital apices, the right optic nerve, and right extraocular muscles. There was enhancement of the cavernous sinuses, right pterygopalatine fossa, right sphenoid wing, and right middle cranial fossa dura (Figure 1). ### OUTPUT:

Neurosarcoidosis

['External Eye Disease', 'Ophthalmology', 'Orbit']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A Black man in his early 70s with a history of coronary artery disease after coronary artery bypass operations, hypertension, and colon polyps presented to oculoplastic surgery with 1 week of progressive right-sided proptosis and headache, described as severe pain radiating to the back of his head. This was associated with right eyelid ptosis and blurry vision. Prior to presentation, an outside ophthalmologist treated him with 1 week of oral prednisone, 20 mg/d, for presumed orbital inflammation with no improvement. He denied additional symptoms. Notably, he described headache and sudden vision loss in the right eye after coronary artery bypass grafting 1 year ago for several days before spontaneous improvement with incomplete resolution. Personal and family histories were negative for malignant neoplasm and autoimmune disease. Examination revealed right-sided uncorrected Snellen visual acuity of 20/60 associated with restricted supraduction, abduction, and infraduction. Pupils were equal in size without a relative afferent pupillary defect, and intraocular pressures were 10 mm Hg OD and 11 mm Hg OS. Visual fields had temporal restriction to confrontation of the right eye. Vision, motility, and visual fields were normal on the left. Pertinent findings included right-sided proptosis of 2 mm, cranial nerve V1 and V2 hypoesthesia, eyelid ptosis with a margin to reflex distance 1 of 0 mm, optic disc pallor, and vessel attenuation. Outside magnetic resonance imaging (MRI) demonstrated an infiltrative mass involving right greater than left orbital apices, the right optic nerve, and right extraocular muscles. There was enhancement of the cavernous sinuses, right pterygopalatine fossa, right sphenoid wing, and right middle cranial fossa dura (Figure 1). ### OUTPUT:

JAMA_FINAL254

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 60-year-old man presented with a 1-week history of progressive painless diplopia. He had a history of hypothyroidism and dyslipidemia, for which he took levothyroxine and rosuvastatin. He reported no changes in visual acuity or color vision; no ocular pain, erythema, or abnormal discharge; and no headaches, scalp tenderness, jaw claudication, ptosis, dysphagia, dysarthria, weakness, numbness, or ataxia. He did not have any constitutional or systemic symptoms. Physical examination showed an isolated limitation of right eye abduction. The remainder of the examination, including visual acuity, pupillary reaction, visual fields, and fundoscopy, was unremarkable. A magnetic resonance image (MRI) of the head showed abnormal thickening and T2 hyperintensity of the right lateral rectus muscle with T1-weighted gadolinium enhancement (Figure 1). Tests for infection and autoimmune disease had negative results. Computed tomography of the abdomen and pelvis did not demonstrate any evidence of malignancy. ### OUTPUT:

IgG4-related disease

['External Eye Disease', 'Neuro-ophthalmology', 'Neurology', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 60-year-old woman presented with a 1-week history of progressive painless diplopia. She had a history of hypothyroidism and dyslipidemia, for which she took levothyroxine and rosuvastatin. She reported no changes in visual acuity or color vision; no ocular pain, erythema, or abnormal discharge; and no headaches, scalp tenderness, jaw claudication, ptosis, dysphagia, dysarthria, weakness, numbness, or ataxia. She did not have any constitutional or systemic symptoms. Physical examination showed an isolated limitation of right eye abduction. The remainder of the examination, including visual acuity, pupillary reaction, visual fields, and fundoscopy, was unremarkable. A magnetic resonance image (MRI) of the head showed abnormal thickening and T2 hyperintensity of the right lateral rectus muscle with T1-weighted gadolinium enhancement (Figure 1). Tests for infection and autoimmune disease had negative results. Computed tomography of the abdomen and pelvis did not demonstrate any evidence of malignancy. ### OUTPUT:

JAMA_FINAL255

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 60-year-old man incarcerated in Ohio presented to the emergency department after a syncopal episode. He reported recent exposure to COVID-19 but had no fevers, chest pain, cough, dyspnea, or diarrhea. He had unintentionally lost 13.6 kg over 2 years. His temperature was 37 °C (98.5 °F); blood pressure, 124/75 mm Hg; pulse, 123/min; respiratory rate, 22/min; and oxygen saturation, 96% on room air. Findings on physical examination were unremarkable. His white blood cell count was 3300/μL (reference, 4500-11 000/μL) with an absolute lymphocyte count of 200/μL (reference, 1000-4800/μL). Chest radiograph showed bilateral reticulonodular opacities. He was hospitalized and treated with azithromycin, remdesivir, and dexamethasone despite 3 negative SARS-CoV-2 polymerase chain reaction (PCR) test results. Two days after hospital discharge, he presented to the emergency department with recurrent syncope. His temperature was 38.1 °C (100.6 °F); blood pressure, 122/82 mm Hg; pulse, 135/min; and oxygen saturation, 86% on room air. A computed tomography scan revealed diffuse bilateral pulmonary micronodular opacities, a 2.2-cm nodule in the lingula, and mediastinal and hilar lymphadenopathy (Figure 1). Results of HIV testing were positive for HIV-1 antibodies. ### OUTPUT:

Disseminated histoplasmosis

['Pulmonary Medicine', 'Radiology', 'HIV', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 60-year-old woman incarcerated in Ohio presented to the emergency department after a syncopal episode. She reported recent exposure to COVID-19 but had no fevers, chest pain, cough, dyspnea, or diarrhea. She had unintentionally lost 13.6 kg over 2 years. Her temperature was 37 °C (98.5 °F); blood pressure, 124/75 mm Hg; pulse, 123/min; respiratory rate, 22/min; and oxygen saturation, 96% on room air. Findings on physical examination were unremarkable. Her white blood cell count was 3300/μL (reference, 4500-11 000/μL) with an absolute lymphocyte count of 200/μL (reference, 1000-4800/μL). Chest radiograph showed bilateral reticulonodular opacities. She was hospitalized and treated with azithromycin, remdesivir, and dexamethasone despite 3 negative SARS-CoV-2 polymerase chain reaction (PCR) test results. Two days after hospital discharge, she presented to the emergency department with recurrent syncope. Her temperature was 38.1 °C (100.6 °F); blood pressure, 122/82 mm Hg; pulse, 135/min; and oxygen saturation, 86% on room air. A computed tomography scan revealed diffuse bilateral pulmonary micronodular opacities, a 2.2-cm nodule in the lingula, and mediastinal and hilar lymphadenopathy (Figure 1). Results of HIV testing were positive for HIV-1 antibodies. ### OUTPUT:

JAMA_FINAL256

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old woman presented with a several-week history of a painless right-sided swelling on her anterior neck. She denied trauma, recent illnesses, respiratory symptoms, dysphagia, oral lesions, hemoptysis, fever, fatigue, weight loss, and night sweats. She had an unremarkable medical history without history of hypothyroidism or hyperthyroidism, cancer, chemotherapy, radiation, or tuberculosis. She denied alcohol, tobacco, or current medication use. Her family history included a sibling with sarcoma in their 50s. On examination, a 4.0-cm mobile, nontender right lower anterior neck mass was palpated in a suprasternal location. No lymphadenopathy was noted. Laboratory results showed normal serum calcium levels and leukocyte counts. Initial ultrasonography showed a 4.2-cm solid nodule adjacent to the lower pole of the right thyroid. Computed tomography results of the neck showed a 3.4-cm circumscribed, heterogenous, hypodense, enhancing mass that was abutting the inferior right thyroid and at the right lateral margin of the trachea. The mass was just medial to the right common carotid, causing left lateral displacement of the trachea (Figure 1). ### OUTPUT:

Thymoma

['Radiology', 'Oncology', 'Endocrine Cancer', 'Hematologic Cancer', 'Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 58-year-old man presented with a several-week history of a painless right-sided swelling on his anterior neck. He denied trauma, recent illnesses, respiratory symptoms, dysphagia, oral lesions, hemoptysis, fever, fatigue, weight loss, and night sweats. He had an unremarkable medical history without history of hypothyroidism or hyperthyroidism, cancer, chemotherapy, radiation, or tuberculosis. He denied alcohol, tobacco, or current medication use. His family history included a sibling with sarcoma in their 50s. On examination, a 4.0-cm mobile, nontender right lower anterior neck mass was palpated in a suprasternal location. No lymphadenopathy was noted. Laboratory results showed normal serum calcium levels and leukocyte counts. Initial ultrasonography showed a 4.2-cm solid nodule adjacent to the lower pole of the right thyroid. Computed tomography results of the neck showed a 3.4-cm circumscribed, heterogenous, hypodense, enhancing mass that was abutting the inferior right thyroid and at the right lateral margin of the trachea. The mass was just medial to the right common carotid, causing left lateral displacement of the trachea (Figure 1). ### OUTPUT:

JAMA_FINAL257

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 82-year-old with hereditary hemorrhagic telangiectasia and history of past cigarette smoking presented to pulmonary clinic for evaluation of dyspnea that had worsened over the previous 5 years. Two years prior, he was diagnosed with a right lower lobe segmental pulmonary embolism on a computed tomography (CT) pulmonary angiogram after evaluation of shortness of breath. Warfarin was initiated but discontinued after 2 months due to recurrent epistaxis. On presentation to the pulmonary clinic, the patient reported dyspnea with minimal activity, fatigue, lightheadedness, and leg swelling. His temperature was 96.8 °F (36 °C); blood pressure, 120/71 mm Hg; heart rate, 73/min; and oxygen saturation, 98% on room air. He appeared frail and had multiple telangiectasias on his lips, tongue, and hands. He had jugular venous distension, a cardiac systolic murmur, right ventricular heave, and bilateral lower extremity edema to the knees. Laboratory testing revealed brain-type natriuretic peptide level of 1333 pg/mL (reference, <100 pg/mL) and hemoglobin level of 12.9 g/dL (reference, 13.9-16.3 g/dL). During a 6-minute walk test on room air, his oxygen saturation decreased to 87%. With oxygen delivered by nasal cannula at 4 L/min, his oxygen saturation was 98%, and he walked 90 m (15% of predicted). An echocardiogram showed a normal left ventricular ejection fraction, moderate-severe right ventricular dilatation, and right ventricular systolic pressure of 60 to 70 mm Hg (reference, 35-40 mm Hg). Findings on an echocardiogram performed 10 years prior were normal. ### OUTPUT:

Chronic thromboembolic pulmonary hypertension (CTEPH)

['Cardiology', 'Emergency Medicine', 'Geriatrics', 'Pulmonary Medicine', 'Venous Thromboembolism']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 82-year-old with hereditary hemorrhagic telangiectasia and history of past cigarette smoking presented to pulmonary clinic for evaluation of dyspnea that had worsened over the previous 5 years. Two years prior, she was diagnosed with a right lower lobe segmental pulmonary embolism on a computed tomography (CT) pulmonary angiogram after evaluation of shortness of breath. Warfarin was initiated but discontinued after 2 months due to recurrent epistaxis. On presentation to the pulmonary clinic, the patient reported dyspnea with minimal activity, fatigue, lightheadedness, and leg swelling. Her temperature was 96.8 °F (36 °C); blood pressure, 120/71 mm Hg; heart rate, 73/min; and oxygen saturation, 98% on room air. She appeared frail and had multiple telangiectasias on her lips, tongue, and hands. She had jugular venous distension, a cardiac systolic murmur, right ventricular heave, and bilateral lower extremity edema to the knees. Laboratory testing revealed brain-type natriuretic peptide level of 1333 pg/mL (reference, <100 pg/mL) and hemoglobin level of 12.9 g/dL (reference, 13.9-16.3 g/dL). During a 6-minute walk test on room air, her oxygen saturation decreased to 87%. With oxygen delivered by nasal cannula at 4 L/min, her oxygen saturation was 98%, and she walked 90 m (15% of predicted). An echocardiogram showed a normal left ventricular ejection fraction, moderate-severe right ventricular dilatation, and right ventricular systolic pressure of 60 to 70 mm Hg (reference, 35-40 mm Hg). Findings on an echocardiogram performed 10 years prior were normal. ### OUTPUT:

JAMA_FINAL258

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old boy with a medical history of allergic rhinitis presented to the emergency department of a children’s hospital with 2 weeks of painful left-sided neck swelling and fever. He had accompanying night sweats, fatigue, and decreased appetite. Initial physical examination revealed multiple distinct matted, firm left-sided cervical lymph nodes. Laboratory evaluation was notable for leukopenia with a white blood cell count of 3700/µL (to convert to 109/L, multiply by 0.001), a microcytic anemia with a hemoglobin of 10.7 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 58 µm3 (to convert to fL, multiply by 1), an elevated lactate dehydrogenase level of 548 U/L (to convert to µkat/L, multiply by 0.0167), and an elevated erythrocyte sedimentation rate of 35 mm/h. Purified protein derivative and infectious mononucleosis testing were negative. A contrast-enhanced neck computed tomography (CT) scan revealed multiple lymph nodes with areas of central hypodensity, and a conglomerate of heterogeneous lymph nodes in the left supraclavicular region (level 5B), measuring approximately 3.7 × 1.4 × 3.6 cm (Figure). The otolaryngology service was consulted, and a left level Va and Vb selective neck dissection was performed. ### OUTPUT:

Kikuchi-Fujimoto disease

['Otolaryngology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 11-year-old girl with a medical history of allergic rhinitis presented to the emergency department of a children’s hospital with 2 weeks of painful left-sided neck swelling and fever. She had accompanying night sweats, fatigue, and decreased appetite. Initial physical examination revealed multiple distinct matted, firm left-sided cervical lymph nodes. Laboratory evaluation was notable for leukopenia with a white blood cell count of 3700/µL (to convert to 109/L, multiply by 0.001), a microcytic anemia with a hemoglobin of 10.7 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 58 µm3 (to convert to fL, multiply by 1), an elevated lactate dehydrogenase level of 548 U/L (to convert to µkat/L, multiply by 0.0167), and an elevated erythrocyte sedimentation rate of 35 mm/h. Purified protein derivative and infectious mononucleosis testing were negative. A contrast-enhanced neck computed tomography (CT) scan revealed multiple lymph nodes with areas of central hypodensity, and a conglomerate of heterogeneous lymph nodes in the left supraclavicular region (level 5B), measuring approximately 3.7 × 1.4 × 3.6 cm (Figure). The otolaryngology service was consulted, and a left level Va and Vb selective neck dissection was performed. ### OUTPUT:

JAMA_FINAL259

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 20s presented to the dermatology department with a monthlong history of gradually progressing papules and nodules on the face, accompanied by fever, fatigue, and weight loss. On physical examination, multiple pink papules and umbilicated nodules were found on the face (Figure 1A). He had a 5-year history of HIV infection but self-discontinued his antiretroviral treatment due to treatment-related gastrointestinal and neurologic reactions 4 years prior. A biopsy specimen was taken for pathological examination (Figure 1B). ### OUTPUT:

Cryptococcosis

['Dermatology', 'Fungal Infections', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 20s presented to the dermatology department with a monthlong history of gradually progressing papules and nodules on the face, accompanied by fever, fatigue, and weight loss. On physical examination, multiple pink papules and umbilicated nodules were found on the face (Figure 1A). She had a 5-year history of HIV infection but self-discontinued her antiretroviral treatment due to treatment-related gastrointestinal and neurologic reactions 4 years prior. A biopsy specimen was taken for pathological examination (Figure 1B). ### OUTPUT:

JAMA_FINAL260

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s with previous breast carcinoma diagnosed 11 years prior, currently in complete remission, presented with pruritic lesions on her upper body. Physical examination revealed more than 10 monomorphous, 5- to 10-mm, pink papules with telangiectasias and white background on dermoscopy, distributed on the chest, arms, and back (Figure 1). There were palmoplantar keratosis and pits. The patient underwent thyroid ultrasonography, abdominal ultrasonography, colonoscopy, and central nervous system magnetic resonance imaging. These explorations revealed 1 Thyroid Imaging Reporting and Data System (TI-RADS) level 5 lesion, a kidney mass, and more than 100 colonic polyps. ### OUTPUT:

Cowden syndrome

['Dermatology', 'Gastroenterology', 'Gastrointestinal Cancer', 'Genetics and Genomics', 'Cancer Genetics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s with previous breast carcinoma diagnosed 11 years prior, currently in complete remission, presented with pruritic lesions on his upper body. Physical examination revealed more than 10 monomorphous, 5- to 10-mm, pink papules with telangiectasias and white background on dermoscopy, distributed on the chest, arms, and back (Figure 1). There were palmoplantar keratosis and pits. The patient underwent thyroid ultrasonography, abdominal ultrasonography, colonoscopy, and central nervous system magnetic resonance imaging. These explorations revealed 1 Thyroid Imaging Reporting and Data System (TI-RADS) level 5 lesion, a kidney mass, and more than 100 colonic polyps. ### OUTPUT:

JAMA_FINAL261

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen. ### OUTPUT:

Mpox

['Dermatology', 'Pathology and Laboratory Medicine', 'Mpox (Monkeypox)']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to her significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen. ### OUTPUT:

JAMA_FINAL262

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory. On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy. On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies. ### OUTPUT:

Kikuchi-Fujimoto disease

['Pain Medicine', 'Infectious Diseases', 'Antibiotic Use, Overuse, Resistance, Stewardship']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 28-year-old man presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. He denied recent travel, sick contacts, or autoimmune disease. His medical history was significant for α-thalassemia but otherwise noncontributory. On examination, he had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. He was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over his face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given his persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy. On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies. ### OUTPUT:

JAMA_FINAL263

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis. ### OUTPUT:

Cardiac sarcoidosis

['Geriatrics', 'Heart Failure', 'Cardiac Imaging', 'Rhythm Disorders', 'Cardiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. He had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, he had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and his vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with his previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis. ### OUTPUT:

JAMA_FINAL264

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains. ### OUTPUT:

Diffuse-type neurofibroma

['Headache', 'Neurology', 'Pain Medicine', 'Neuromuscular Diseases', 'Neuropathy']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 27-year-old man presented to his primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on his left scalp, which he had initially noted in high school. He denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and he only reported pain with prolonged pressure. On his scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains. ### OUTPUT:

JAMA_FINAL265

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria. Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C). ### OUTPUT:

Phaeohyphomycosis

['Dermatology', 'Facial Plastic Surgery', 'Fungal Infections', 'Global Health', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria. Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C). ### OUTPUT:

JAMA_FINAL266

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy 13-month-old male was scheduled to undergo excisional biopsy of a left anterior tongue submucosal intramuscular mass (Figure 1). This firm-to-palpation mass was noted at birth and remained proportional in size with the child’s somatic growth, measuring approximately 1 cm in diameter on presentation. Preoperative magnetic resonance imaging (MRI) documented the mass to be uniformly solid and well circumscribed without cystic components or flow voids, hypointense on T2, and hyperintense with homogeneous contrast enhancement on T1. His head, neck, and general examination findings were otherwise normal with no cervical lymphadenopathy or additional masses. ### OUTPUT:

Rhabdomyoma

['Otolaryngology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: Final diagnosis: Rhabdomyoma. Case report: An otherwise healthy 13-month-old female was scheduled to undergo excisional biopsy of a left anterior tongue submucosal intramuscular mass (Figure 1). This firm-to-palpation mass was noted at birth and remained proportional in size with the child’s somatic growth, measuring approximately 1 cm in diameter on presentation. Preoperative magnetic resonance imaging (MRI) documented the mass to be uniformly solid and well circumscribed without cystic components or flow voids, hypointense on T2, and hyperintense with homogeneous contrast enhancement on T1. Her head, neck, and general examination findings were otherwise normal with no cervical lymphadenopathy or additional masses. ### OUTPUT:

JAMA_FINAL267

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old girl with a 7-day history of painless vision loss and central scotoma in her left eye was referred to the department of ophthalmology. Three weeks prior, she had presented with mild fever and flulike symptoms, associated with a severe frontal headache that was mildly relieved by analgesics. Her medical history was positive for relapsing urinary tract infections since early infancy without adequate follow-up. Findings of an ophthalmological examination 1 year prior were reported as normal. At initial examination, she was conscious but somewhat lethargic. Her best-corrected visual acuity was 20/20 OD and 20/80 OS. Pupillary light responses, extrinsic ocular motility, anterior segment biomicroscopy, and intraocular pressure were normal in both eyes. Dilated fundus examination revealed a bilateral sectorial macular star that was more extended in the left eye, with retinal veins slightly dilated and tortuous, attenuated arterioles, some juxta and peripapillary nerve fiber layer infarcts, and optic disc edema with marked papillary telangiectasia; in addition, some faint, small, tan-yellow dots were observed at the level of the retinal pigment epithelium in the posterior pole, some of them already grayish and with a hypopigmented halo (Figure 1). Optical coherence tomography displayed elevated optic discs and hyperreflective material in the outer plexiform layer temporal to the optic disc in both eyes and a macular neurosensory detachment in the left eye. Results of visual field testing were normal in the right eye and showed a central scotoma in the left eye. ### OUTPUT:

Hypertensive retinopathy

['Emergency Medicine', 'Hypertension', 'Urology', 'Retinal Disorders', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 13-year-old boy with a 7-day history of painless vision loss and central scotoma in his left eye was referred to the department of ophthalmology. Three weeks prior, he had presented with mild fever and flulike symptoms, associated with a severe frontal headache that was mildly relieved by analgesics. His medical history was positive for relapsing urinary tract infections since early infancy without adequate follow-up. Findings of an ophthalmological examination 1 year prior were reported as normal. At initial examination, he was conscious but somewhat lethargic. His best-corrected visual acuity was 20/20 OD and 20/80 OS. Pupillary light responses, extrinsic ocular motility, anterior segment biomicroscopy, and intraocular pressure were normal in both eyes. Dilated fundus examination revealed a bilateral sectorial macular star that was more extended in the left eye, with retinal veins slightly dilated and tortuous, attenuated arterioles, some juxta and peripapillary nerve fiber layer infarcts, and optic disc edema with marked papillary telangiectasia; in addition, some faint, small, tan-yellow dots were observed at the level of the retinal pigment epithelium in the posterior pole, some of them already grayish and with a hypopigmented halo (Figure 1). Optical coherence tomography displayed elevated optic discs and hyperreflective material in the outer plexiform layer temporal to the optic disc in both eyes and a macular neurosensory detachment in the left eye. Results of visual field testing were normal in the right eye and showed a central scotoma in the left eye. ### OUTPUT:

JAMA_FINAL268

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 62-year-old healthy man with no recent travel history or sick contacts presented with 2 weeks of midline sore throat without systemic signs, such as fever, myalgia, or rash. A physical examination, including flexible laryngoscopy, revealed cobbling, adherent, thick yellow mucus and ulceration of the uvula (Figure 1A). ### OUTPUT:

Leishmaniasis

['Dermatology', 'Otolaryngology', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 62-year-old healthy woman with no recent travel history or sick contacts presented with 2 weeks of midline sore throat without systemic signs, such as fever, myalgia, or rash. A physical examination, including flexible laryngoscopy, revealed cobbling, adherent, thick yellow mucus and ulceration of the uvula (Figure 1A). ### OUTPUT:

JAMA_FINAL269

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 64-year-old man with a 2-year history of seizure disorder presented to the emergency department (ED) at an outside hospital with breakthrough seizures. One month prior to his ED visit, he had been treated with oral antibiotics when he presented to an urgent care center with left-sided otorrhea, otalgia, and hearing loss. In the ED, he denied headaches, fever, otalgia, otorrhea, or hearing loss. Magnetic resonance imaging of the brain with contrast showed diffuse enhancement and possible coalescence in the left mastoid process with adjacent dural enhancement and sigmoid sinus occlusion. He received intravenous vancomycin and cefepime and was started on a heparin drip before being transferred to our facility. On presentation at our facility, the patient appeared well with normal vital signs. There was no periauricular swelling or erythema. Otoscopic examination showed no inflammation of the external auditory canals, and the tympanic membranes were translucent without evidence of retraction or effusion. Computed tomographic venogram confirmed occlusion of the left transverse and sigmoid sinuses, and computed tomography of the temporal bone showed coalescence of mastoid air cells with erosion into the sigmoid sinus. Mastoidectomy was performed for biopsy and culture specimens. Histologic findings from the specimens demonstrated cells with oval nuclei and abundant cytoplasm arranged in syncytial clusters with occasional whorls, pseudoinclusions, and psammomatous calcifications (Figure, A). Immunohistochemical stains were positive for epithelial membrane antigen (EMA) and vimentin (Figure, B). ### OUTPUT:

Meningioma

['Otolaryngology', 'Otology', 'Epilepsy and Seizures', 'Neurology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 64-year-old woman with a 2-year history of seizure disorder presented to the emergency department (ED) at an outside hospital with breakthrough seizures. One month prior to her ED visit, she had been treated with oral antibiotics when she presented to an urgent care center with left-sided otorrhea, otalgia, and hearing loss. In the ED, she denied headaches, fever, otalgia, otorrhea, or hearing loss. Magnetic resonance imaging of the brain with contrast showed diffuse enhancement and possible coalescence in the left mastoid process with adjacent dural enhancement and sigmoid sinus occlusion. She received intravenous vancomycin and cefepime and was started on a heparin drip before being transferred to our facility. On presentation at our facility, the patient appeared well with normal vital signs. There was no periauricular swelling or erythema. Otoscopic examination showed no inflammation of the external auditory canals, and the tympanic membranes were translucent without evidence of retraction or effusion. Computed tomographic venogram confirmed occlusion of the left transverse and sigmoid sinuses, and computed tomography of the temporal bone showed coalescence of mastoid air cells with erosion into the sigmoid sinus. Mastoidectomy was performed for biopsy and culture specimens. Histologic findings from the specimens demonstrated cells with oval nuclei and abundant cytoplasm arranged in syncytial clusters with occasional whorls, pseudoinclusions, and psammomatous calcifications (Figure, A). Immunohistochemical stains were positive for epithelial membrane antigen (EMA) and vimentin (Figure, B). ### OUTPUT:

JAMA_FINAL270

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 53-year-old woman with a history of stage IVA1 (T4N1M0B2) mycosis fungoides presented with a new 1-month history of hyperpigmentation of the oral mucosa (Figure 1). Examination of the mouth revealed multiple coalescing painless nonpruritic black macules and patches on the tongue, roof of the mouth, and buccal mucosa. Examination of the skin was notable for erythematous and hyperpigmented patches covering 90% of the body surface area, consistent with her known mycosis fungoides. Other notable findings on examination were 1- to 2-cm lymphadenopathy in the bilateral inguinal folds and axillae. Review of systems was notable for fatigue. The patient had previously received 5 cycles of romidepsin with progression of disease, followed by 4 doses of pegylated liposomal doxorubicin hydrochloride, which was followed by partial response. ### OUTPUT:

Medication adverse effect

['Hematology', 'Oncology', 'Otolaryngology', 'Hematologic Cancer', 'Lymphomas']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 53-year-old man with a history of stage IVA1 (T4N1M0B2) mycosis fungoides presented with a new 1-month history of hyperpigmentation of the oral mucosa (Figure 1). Examination of the mouth revealed multiple coalescing painless nonpruritic black macules and patches on the tongue, roof of the mouth, and buccal mucosa. Examination of the skin was notable for erythematous and hyperpigmented patches covering 90% of the body surface area, consistent with his known mycosis fungoides. Other notable findings on examination were 1- to 2-cm lymphadenopathy in the bilateral inguinal folds and axillae. Review of systems was notable for fatigue. The patient had previously received 5 cycles of romidepsin with progression of disease, followed by 4 doses of pegylated liposomal doxorubicin hydrochloride, which was followed by partial response. ### OUTPUT:

JAMA_FINAL271

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 7-year-old boy was admitted to the hospital with 1 week of temperatures up to 40.2 °C (104.4 °F), productive cough, and lethargy, which did not improve after 3 days of oral cefuroxime. He lived in rural China and had close contact with dogs, cattle, and sheep. His blood pressure was 93/60 mm Hg; heart rate, 100/min; respiratory rate, 26/min; and oxygen saturation, 94% on room air. Lung auscultation revealed absent breath sounds on the right hemithorax. His abdomen was soft and nontender, without hepatosplenomegaly. His white blood cell count was 8000/μL, with 25.8% eosinophils (reference range, 0%-9%). C-reactive protein level and results from tuberculin skin test, interferon-γ release assay, nucleic acid amplification testing for tuberculosis, acid-fast bacilli smear microscopy, and HIV antibody testing were normal. A thoracoabdominal computed tomography (CT) scan showed a ruptured 10 × 9 × 5–cm right upper lobe pulmonary cyst compressing the right main bronchus and 3 liver cysts (Figure 1). ### OUTPUT:

Cystic echinococcosis

['Pulmonary Medicine', 'Hepatobiliary Disease', 'Gastroenterology and Hepatology', 'Infectious Diseases', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 7-year-old girl was admitted to the hospital with 1 week of temperatures up to 40.2 °C (104.4 °F), productive cough, and lethargy, which did not improve after 3 days of oral cefuroxime. She lived in rural China and had close contact with dogs, cattle, and sheep. Her blood pressure was 93/60 mm Hg; heart rate, 100/min; respiratory rate, 26/min; and oxygen saturation, 94% on room air. Lung auscultation revealed absent breath sounds on the right hemithorax. Her abdomen was soft and nontender, without hepatosplenomegaly. Her white blood cell count was 8000/μL, with 25.8% eosinophils (reference range, 0%-9%). C-reactive protein level and results from tuberculin skin test, interferon-γ release assay, nucleic acid amplification testing for tuberculosis, acid-fast bacilli smear microscopy, and HIV antibody testing were normal. A thoracoabdominal computed tomography (CT) scan showed a ruptured 10 × 9 × 5–cm right upper lobe pulmonary cyst compressing the right main bronchus and 3 liver cysts (Figure 1). ### OUTPUT:

JAMA_FINAL272

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy individual in his 20s presented to the dermatology clinic for evaluation of annular skin lesions that appeared first on his right ankle and then on other areas of his body over a 3-month period. He reported numbness and paresthesia in the areas of affected skin and an inability to fully extend his fingers. The patient did not take any prescription medications or herbal supplements and had immigrated to the US from Samoa 4 years prior. Physical examination revealed multiple tattoos and annular erythematous plaques on his face, chest (Figure, left panel), back, arms, and legs. The patient had bilateral palpable thickened auricular and ulnar nerves, claw-hand deformity (Figure, right panel), foot drop bilaterally, and decreased sensation to temperature over the areas of skin plaque. Results of testing for rapid plasma reagin, antinuclear antibodies, and rheumatoid factor were negative. Examination of punch biopsy samples from 2 plaques on his back revealed granulomatous periadnexal and perivascular dermatitis with diffuse granulomatous infiltrate and foamy histiocytes. Findings on acid-fast bacilli stains and mycobacterial polymerase chain reaction (PCR) testing were negative. Repeat biopsy of a skin plaque revealed no fungal organisms, and Mycobacterium leprae was not identified on Fite Faraco stain. ### OUTPUT:

Multibacillary leprosy

['Dermatology', 'Infectious Diseases', 'Neuropathy']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy individual in her 20s presented to the dermatology clinic for evaluation of annular skin lesions that appeared first on her right ankle and then on other areas of her body over a 3-month period. She reported numbness and paresthesia in the areas of affected skin and an inability to fully extend her fingers. The patient did not take any prescription medications or herbal supplements and had immigrated to the US from Samoa 4 years prior. Physical examination revealed multiple tattoos and annular erythematous plaques on her face, chest (Figure, left panel), back, arms, and legs. The patient had bilateral palpable thickened auricular and ulnar nerves, claw-hand deformity (Figure, right panel), foot drop bilaterally, and decreased sensation to temperature over the areas of skin plaque. Results of testing for rapid plasma reagin, antinuclear antibodies, and rheumatoid factor were negative. Examination of punch biopsy samples from 2 plaques on her back revealed granulomatous periadnexal and perivascular dermatitis with diffuse granulomatous infiltrate and foamy histiocytes. Findings on acid-fast bacilli stains and mycobacterial polymerase chain reaction (PCR) testing were negative. Repeat biopsy of a skin plaque revealed no fungal organisms, and Mycobacterium leprae was not identified on Fite Faraco stain. ### OUTPUT:

JAMA_FINAL273

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-year-old girl with no medical history presented to the emergency department with 1 day of abnormal gait and bilateral mydriasis. Two weeks prior, she had upper respiratory symptoms and bacterial conjunctivitis treated with topical ofloxacin. On examination, pupils were fixed and dilated to 8 mm, extraocular movements were intact, and fundus examination was normal. She had brisk reflexes, poor coordination, and a wide-based unsteady gait. Bloodwork revealed leukocytosis and an elevated erythrocyte sedimentation rate; cultures remained without growth. Lumbar puncture with cerebrospinal fluid studies, computed tomography scan, and magnetic resonance imaging of brain and orbits were normal. The patient was discharged 3 days later following improvement in lethargy and gait with a diagnosis of acute cerebellar ataxia. When she presented to ophthalmology for 1-week follow-up, her visual acuity was central, steady, and maintained in both eyes. She demonstrated sluggish but reactive pupils and new-onset ophthalmoplegia. She was unable to move either eye in any direction, including with doll’s head maneuver. She was readmitted to the hospital and demonstrated diminished reflexes bilaterally and unsteady gait. Repeat magnetic resonance imaging demonstrated diffuse enhancement of the lower thoracic and cauda equina nerve roots and enhancement of the left oculomotor nerve (Figure). ### OUTPUT:

Miller Fisher syndrome

['Demyelinating Disorders', 'Neuro-ophthalmology', 'Neurology', 'Ophthalmology', 'Pediatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-year-old boy with no medical history presented to the emergency department with 1 day of abnormal gait and bilateral mydriasis. Two weeks prior, he had upper respiratory symptoms and bacterial conjunctivitis treated with topical ofloxacin. On examination, pupils were fixed and dilated to 8 mm, extraocular movements were intact, and fundus examination was normal. He had brisk reflexes, poor coordination, and a wide-based unsteady gait. Bloodwork revealed leukocytosis and an elevated erythrocyte sedimentation rate; cultures remained without growth. Lumbar puncture with cerebrospinal fluid studies, computed tomography scan, and magnetic resonance imaging of brain and orbits were normal. The patient was discharged 3 days later following improvement in lethargy and gait with a diagnosis of acute cerebellar ataxia. When he presented to ophthalmology for 1-week follow-up, his visual acuity was central, steady, and maintained in both eyes. He demonstrated sluggish but reactive pupils and new-onset ophthalmoplegia. He was unable to move either eye in any direction, including with doll’s head maneuver. He was readmitted to the hospital and demonstrated diminished reflexes bilaterally and unsteady gait. Repeat magnetic resonance imaging demonstrated diffuse enhancement of the lower thoracic and cauda equina nerve roots and enhancement of the left oculomotor nerve (Figure). ### OUTPUT:

JAMA_FINAL274

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old man presented with a left shoulder mass. It began with a quarter-size maculopapular lesion and continued to progress during the next 3 years. He reported limited shoulder movements and denied other symptoms. There was no medical or surgical history, and he had a negative personal or familial oncologic history. The patient was a construction worker and used tobacco daily. On physical examination, there was a 24 × 15-cm fungating, necrotic, and ulcerated left shoulder mass (Figure 1A). A punch biopsy showed sheets of highly pleomorphic atypical spindle and epithelial cells within the superficial and deep dermis, extending into the subcutaneous tissue, and with 18 mitoses/mm2. Immunohistochemistry demonstrated SOX10-positive and pankeratin-negative tumor cells. A whole-body positron emission tomographic and computed tomographic scan revealed an intensely hypermetabolic left shoulder mass and multiple hypermetabolic enlarged left axillary lymph nodes, with no distant metastases (Figure 1B). Brain magnetic resonance imaging was negative for intracranial metastasis. ### OUTPUT:

Melanoma

['Dermatology', 'Genetics and Genomics', 'Oncology', 'Skin Cancer', 'Cancer Genetics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 46-year-old woman presented with a left shoulder mass. It began with a quarter-size maculopapular lesion and continued to progress during the next 3 years. She reported limited shoulder movements and denied other symptoms. There was no medical or surgical history, and she had a negative personal or familial oncologic history. The patient was a construction worker and used tobacco daily. On physical examination, there was a 24 × 15-cm fungating, necrotic, and ulcerated left shoulder mass (Figure 1A). A punch biopsy showed sheets of highly pleomorphic atypical spindle and epithelial cells within the superficial and deep dermis, extending into the subcutaneous tissue, and with 18 mitoses/mm2. Immunohistochemistry demonstrated SOX10-positive and pankeratin-negative tumor cells. A whole-body positron emission tomographic and computed tomographic scan revealed an intensely hypermetabolic left shoulder mass and multiple hypermetabolic enlarged left axillary lymph nodes, with no distant metastases (Figure 1B). Brain magnetic resonance imaging was negative for intracranial metastasis. ### OUTPUT:

JAMA_FINAL275

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-year child presented with headache for 1 month and seizures followed by altered consciousness for 1 day. He had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character. Occasionally, the headache became severe accompanied by vomiting, photophobia, and phonophobia. The child had 4 to 5 episodes of generalized tonic-clonic seizures 1 day prior to admission. He remained unconscious for several hours and spontaneously regained consciousness over 24 hours. There was no history of fever, weight loss, limb weakness, vision impairment, or any strokelike illness. His birth and developmental history were unremarkable. On examination, his pulse rate was 80 beats per minute (regular) with all peripheral pulses palpable without any radio-femoral delay. His blood pressure was 170/110 mm Hg with less than 10 mm Hg difference of systolic and diastolic blood pressure in other limbs. Abdominal examination revealed abdominal bruit. Fundus examination revealed papilledema with changes of hypertensive retinopathy. He was not oriented to place and time. The cranial nerves, motor, sensory, and autonomic system examination were unremarkable. Meningeal signs were absent. There was no evidence of neurocutaneous markers. His cranial magnetic resonance imaging revealed bilateral white matter hyperintensity that was more marked in the bilateral parieto-occipital region. Ultrasound of the abdomen revealed a small right kidney and renal Doppler was suggestive of right renal-artery stenosis. His computed tomography angiography revealed short segment (3 cm) and short circumferential thickening of the descending aorta with right renal artery narrowing (Figure 1). His repeat cranial magnetic resonance imaging showed significant reduction in the white matter hyperintensities. ### OUTPUT:

Takayasu arteritis

['Pediatrics', 'Rheumatology', 'Neurology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 6-year child presented with headache for 1 month and seizures followed by altered consciousness for 1 day. She had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character. Occasionally, the headache became severe accompanied by vomiting, photophobia, and phonophobia. The child had 4 to 5 episodes of generalized tonic-clonic seizures 1 day prior to admission. She remained unconscious for several hours and spontaneously regained consciousness over 24 hours. There was no history of fever, weight loss, limb weakness, vision impairment, or any strokelike illness. Her birth and developmental history were unremarkable. On examination, her pulse rate was 80 beats per minute (regular) with all peripheral pulses palpable without any radio-femoral delay. Her blood pressure was 170/110 mm Hg with less than 10 mm Hg difference of systolic and diastolic blood pressure in other limbs. Abdominal examination revealed abdominal bruit. Fundus examination revealed papilledema with changes of hypertensive retinopathy. She was not oriented to place and time. The cranial nerves, motor, sensory, and autonomic system examination were unremarkable. Meningeal signs were absent. There was no evidence of neurocutaneous markers. Her cranial magnetic resonance imaging revealed bilateral white matter hyperintensity that was more marked in the bilateral parieto-occipital region. Ultrasound of the abdomen revealed a small right kidney and renal Doppler was suggestive of right renal-artery stenosis. Her computed tomography angiography revealed short segment (3 cm) and short circumferential thickening of the descending aorta with right renal artery narrowing (Figure 1). Her repeat cranial magnetic resonance imaging showed significant reduction in the white matter hyperintensities. ### OUTPUT:

JAMA_FINAL276

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old woman presented to the otolaryngology clinic for evaluation of a parapharyngeal space (PPS) mass that was incidentally found on magnetic resonance imaging (MRI) of the face. The patient experienced left jaw tightness, aural fullness, and facial discomfort. The MRI results demonstrated a well-circumscribed, ovoid mass in the left prestyloid PPS that measured 12 × 15 × 22 mm. The lesion was isointense on T1-weighted imaging, was hyperintense on T2-weighted imaging, and demonstrated heterogeneous enhancement following gadolinium administration (Figure 1). A computed tomography–guided fine-needle aspiration was performed, which demonstrated blood, fibrin, and rare mesenchymal cells. Given her ongoing symptoms, the patient requested surgical resection. The patient underwent transoral robotic surgery for resection of her PPS mass to achieve definitive diagnosis and treatment. Histopathologic evaluation demonstrated a well-circumscribed, 12-mm mass. ### OUTPUT:

Venous malformation

['Minimally Invasive Surgery', 'Otolaryngology', 'Head and Neck Surgery', 'Radiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 71-year-old man presented to the otolaryngology clinic for evaluation of a parapharyngeal space (PPS) mass that was incidentally found on magnetic resonance imaging (MRI) of the face. The patient experienced left jaw tightness, aural fullness, and facial discomfort. The MRI results demonstrated a well-circumscribed, ovoid mass in the left prestyloid PPS that measured 12 × 15 × 22 mm. The lesion was isointense on T1-weighted imaging, was hyperintense on T2-weighted imaging, and demonstrated heterogeneous enhancement following gadolinium administration (Figure 1). A computed tomography–guided fine-needle aspiration was performed, which demonstrated blood, fibrin, and rare mesenchymal cells. Given his ongoing symptoms, the patient requested surgical resection. The patient underwent transoral robotic surgery for resection of his PPS mass to achieve definitive diagnosis and treatment. Histopathologic evaluation demonstrated a well-circumscribed, 12-mm mass. ### OUTPUT:

JAMA_FINAL277

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 70-year-old woman with hypertension, atrial fibrillation, congestive heart failure, and gallstones presented to the emergency department with 3 days of nausea, vomiting, and abdominal pain. She reported no hematemesis, hematochezia, or melena and had no history of abdominal surgery. On admission to the emergency department, she was afebrile, her blood pressure was 80/60 mm Hg, and heart rate was 122/min. On physical examination, her abdomen was distended, tympanic, and slightly tender to palpation diffusely. Blood testing showed a white blood cell count of 10 450/μL (84.1% neutrophils); C-reactive protein level, 9.5 mg/dL; potassium level, 3.0 mEq/L (reference, 3.6-5.2 mEq/L); and creatinine level, 5.57 mg/dL (429.39 μmol/L, up from a baseline level of 0.80 mg/dL [70.72 μmol/L]). Sodium and liver function values were normal. In the emergency department, she received a 500-mL bolus of intravenous crystalloid fluid and 1 g of intravenous ceftriaxone. A nasogastric tube was placed and initially drained 300 mL of biliary fluid. A non–contrast-enhanced abdominal computed tomography (CT) scan was performed (Figure 1). ### OUTPUT:

Gallstone ileus

['Surgery', 'Hepatobiliary Surgery', 'Hepatobiliary Disease', 'Gastroenterology and Hepatology', 'Radiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 70-year-old man with hypertension, atrial fibrillation, congestive heart failure, and gallstones presented to the emergency department with 3 days of nausea, vomiting, and abdominal pain. He reported no hematemesis, hematochezia, or melena and had no history of abdominal surgery. On admission to the emergency department, he was afebrile, his blood pressure was 80/60 mm Hg, and heart rate was 122/min. On physical examination, his abdomen was distended, tympanic, and slightly tender to palpation diffusely. Blood testing showed a white blood cell count of 10 450/μL (84.1% neutrophils); C-reactive protein level, 9.5 mg/dL; potassium level, 3.0 mEq/L (reference, 3.6-5.2 mEq/L); and creatinine level, 5.57 mg/dL (429.39 μmol/L, up from a baseline level of 0.80 mg/dL [70.72 μmol/L]). Sodium and liver function values were normal. In the emergency department, he received a 500-mL bolus of intravenous crystalloid fluid and 1 g of intravenous ceftriaxone. A nasogastric tube was placed and initially drained 300 mL of biliary fluid. A non–contrast-enhanced abdominal computed tomography (CT) scan was performed (Figure 1). ### OUTPUT:

JAMA_FINAL278

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old man with myelodysplastic syndrome (MDS) with isolated deletion 5q (del5q) presented with multiple nonhealing skin ulcers on the chest and upper extremities. Four years earlier, he started taking lenalidomide, 10 mg/d (28-day cycle), to treat worsening anemia; after 2 cycles of treatment, he became transfusion independent. Since then, he has remained stable with the same dose and schedule of lenalidomide without significant adverse effects. The presenting skin lesions developed 1 month before presentation and began as small pustules that rapidly transformed into painful ulcers. He was treated with valacyclovir for a presumed diagnosis of shingles, but the lesions did not improve. Because of suspected necrotizing fasciitis, he underwent incision and drainage of the lesions. Cultures from the surgical specimen grew methicillin-resistant Staphylococcus hemolyticus. However, the lesions continued to worsen despite vancomycin and additional debridement. Thus, he was transferred to our facility. Physical examination showed multiple cutaneous ulcers with gray undermined borders and red papules of varying depths involving the chest, back, and upper extremity; lesions were as large as 9 × 15 cm. A complete blood cell count showed a white blood cell count of 16.2 × 103/μL (to convert to 109/L, multiply by 1.0) with an absolute neutrophil count of 12.7 × 103/μL, hemoglobin level of 9.4 g/dL (to convert to g/L, multiply by 10.0), and platelet count of 262 × 103/μL with no circulating blasts. Results of additional laboratory studies, including blood culture and tests for herpes zoster virus (via polymerase chain reaction), antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody were all negative. Additionally, the patient also had hypertension and hypercholesterolemia for which he was taking lisinopril and simvastatin, respectively. Pathologic sampling from skin lesions demonstrated a dense dermal infiltrate with predominantly neutrophils along with reactive histiocytes, fibroblasts, and angioplasia (Figure, A). Immunohistochemical staining showed myeloperoxidase-positive neutrophils (Figure, B), histiocytic markers (CD43, CD63, CD168), and CD117-positive mast cells, but no immature myeloid precursors. Results of Grocott-Gomori methenamine silver staining were unremarkable. ### OUTPUT:

Pyoderma gangrenosum

['Dermatology', 'Cutaneous Drug Reactions', 'Clinical Pharmacy and Pharmacology', 'Hematology', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old woman with myelodysplastic syndrome (MDS) with isolated deletion 5q (del5q) presented with multiple nonhealing skin ulcers on the chest and upper extremities. Four years earlier, she started taking lenalidomide, 10 mg/d (28-day cycle), to treat worsening anemia; after 2 cycles of treatment, she became transfusion independent. Since then, she has remained stable with the same dose and schedule of lenalidomide without significant adverse effects. The presenting skin lesions developed 1 month before presentation and began as small pustules that rapidly transformed into painful ulcers. She was treated with valacyclovir for a presumed diagnosis of shingles, but the lesions did not improve. Because of suspected necrotizing fasciitis, she underwent incision and drainage of the lesions. Cultures from the surgical specimen grew methicillin-resistant Staphylococcus hemolyticus. However, the lesions continued to worsen despite vancomycin and additional debridement. Thus, she was transferred to our facility. Physical examination showed multiple cutaneous ulcers with gray undermined borders and red papules of varying depths involving the chest, back, and upper extremity; lesions were as large as 9 × 15 cm. A complete blood cell count showed a white blood cell count of 16.2 × 103/μL (to convert to 109/L, multiply by 1.0) with an absolute neutrophil count of 12.7 × 103/μL, hemoglobin level of 9.4 g/dL (to convert to g/L, multiply by 10.0), and platelet count of 262 × 103/μL with no circulating blasts. Results of additional laboratory studies, including blood culture and tests for herpes zoster virus (via polymerase chain reaction), antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody were all negative. Additionally, the patient also had hypertension and hypercholesterolemia for which she was taking lisinopril and simvastatin, respectively. Pathologic sampling from skin lesions demonstrated a dense dermal infiltrate with predominantly neutrophils along with reactive histiocytes, fibroblasts, and angioplasia (Figure, A). Immunohistochemical staining showed myeloperoxidase-positive neutrophils (Figure, B), histiocytic markers (CD43, CD63, CD168), and CD117-positive mast cells, but no immature myeloid precursors. Results of Grocott-Gomori methenamine silver staining were unremarkable. ### OUTPUT:

JAMA_FINAL279

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A healthy, uncircumcised man in his 30s presented with a 14-year history of dyspareunia and recurrent, purulent discharge from his penis. He had undergone multiple evaluations by dermatologists and urologists and had not responded to systemic antibiotics and topical corticosteroids. Physical examination revealed an erythematous, pinpoint orifice on his glans penis, with peripheral telangiectasias and a linear bluish structure on dermoscopy (Figure, A and B). Ultrasonography revealed a hypoechoic focal zone on the right side of the glans, with multiple hyperechoic bilaminar structures (Figure, C). A biopsy was performed (Figure, D). ### OUTPUT:

Pilonidal sinus

['Dermatology', 'Urology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A healthy, uncircumcised woman in her 30s presented with a 14-year history of dyspareunia and recurrent, purulent discharge from her genital area. She had undergone multiple evaluations by dermatologists and urologists and had not responded to systemic antibiotics and topical corticosteroids. Physical examination revealed an erythematous, pinpoint orifice on her genital area, with peripheral telangiectasias and a linear bluish structure on dermoscopy (Figure, A and B). Ultrasonography revealed a hypoechoic focal zone on the right side of the genital area, with multiple hyperechoic bilaminar structures (Figure, C). A biopsy was performed (Figure, D). ### OUTPUT:

JAMA_FINAL280

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 62-year-old patient presented to the ophthalmology department with sudden painless vision loss in her right eye that occurred 24 hours ago. She also reported a 4-week history of right ear pain and fullness, discomfort over her frontal and maxillary sinuses, and nasal congestion without discharge. Over the past 2 weeks, she had experienced drenching night sweats, cramps in her quadriceps, and weight loss of 3 kg. She denied respiratory symptoms, headaches, scalp tenderness, or jaw claudication. She took no regular medication and did not smoke. At presentation, her visual acuities were perception of light OD and 20/20 OS. There was a right relative afferent pupillary defect. Dilated fundus examination showed a cherry red spot in the right macula with hyperreflectivity and thickening of the inner retinal layers on optical coherence tomography (Figure 1A and B). External eye examination results and ocular motility were normal. Examination by an otolaryngologist revealed normal tympanic membranes and a dry but otherwise normal nasal mucosa on flexible endoscopy. Blood tests showed leukocytosis (white blood cell count, 15 000 /µL; to convert to 109 per liter, multiply by 0.001) with neutrophilia (white blood cell count, 12 500 /µL), elevated C-reactive protein (19.4 mg/dL; to convert to milligrams per liter, multiply by 10), elevated plasma viscosity (2.06 mPas), and thrombocytosis (467 ×103/µL; to convert to ×109 per liter, multiply by 1). Kidney function was within normal limits. Chest radiograph results were unremarkable. ### OUTPUT:

Granulomatosis with polyangiitis

['Otolaryngology', 'Rheumatology', 'Otology', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 62-year-old patient presented to the ophthalmology department with sudden painless vision loss in his right eye that occurred 24 hours ago. He also reported a 4-week history of right ear pain and fullness, discomfort over his frontal and maxillary sinuses, and nasal congestion without discharge. Over the past 2 weeks, he had experienced drenching night sweats, cramps in his quadriceps, and weight loss of 3 kg. He denied respiratory symptoms, headaches, scalp tenderness, or jaw claudication. He took no regular medication and did not smoke. At presentation, his visual acuities were perception of light OD and 20/20 OS. There was a right relative afferent pupillary defect. Dilated fundus examination showed a cherry red spot in the right macula with hyperreflectivity and thickening of the inner retinal layers on optical coherence tomography (Figure 1A and B). External eye examination results and ocular motility were normal. Examination by an otolaryngologist revealed normal tympanic membranes and a dry but otherwise normal nasal mucosa on flexible endoscopy. Blood tests showed leukocytosis (white blood cell count, 15 000 /µL; to convert to 109 per liter, multiply by 0.001) with neutrophilia (white blood cell count, 12 500 /µL), elevated C-reactive protein (19.4 mg/dL; to convert to milligrams per liter, multiply by 10), elevated plasma viscosity (2.06 mPas), and thrombocytosis (467 ×103/µL; to convert to ×109 per liter, multiply by 1). Kidney function was within normal limits. Chest radiograph results were unremarkable. ### OUTPUT:

JAMA_FINAL281

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 25-month-old child with unilateral hearing loss was referred to a pediatric ear, nose, and throat surgeon in a secondary care hospital. Clinical findings suggested unilateral right middle ear effusion associated with ipsilateral conductive hearing loss. After an initial observation period, a right tympanostomy tube was inserted. During the procedure, a clear liquid pulsating from the middle ear was noted, and samples were sent for β-2-transferrine analysis. This confirmed the presence of a cerebrospinal fluid (CSF) leak. The patient was referred to our tertiary referral center hospital. The leak settled with conservative management, and imaging of the brain and skull base was performed. A high-resolution computed tomography scan of the temporal bone showed a lytic aspect of the right temporal bone extending to the petrous apex and the petrous bone, sparing the otic capsule (Figure 1A). There was soft tissue opacification of the right mastoid air cells. Magnetic resonance imaging of the skull base with contrast was performed (Figure 1B). It showed a hyperintense T2 signal in the petrous apex and mastoid air cells. There was a suspected communication into the soft tissues of the right neck in the posterior triangle. Magnetic resonance imaging also showed signs of Chiari malformation type 1. After a skull base multidisciplinary discussion, the patient underwent a bone biopsy through a transmastoid approach. ### OUTPUT:

Gorham-Stout disease

['Otolaryngology', 'Pediatrics', 'Otology', 'Audiology and Hearing']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 25-month-old child with unilateral hearing loss was referred to a pediatric ear, nose, and throat surgeon in a secondary care hospital. Clinical findings suggested unilateral right middle ear effusion associated with ipsilateral conductive hearing loss. After an initial observation period, a right tympanostomy tube was inserted. During the procedure, a clear liquid pulsating from the middle ear was noted, and samples were sent for β-2-transferrine analysis. This confirmed the presence of a cerebrospinal fluid (CSF) leak. The patient was referred to our tertiary referral center hospital. The leak settled with conservative management, and imaging of the brain and skull base was performed. A high-resolution computed tomography scan of the temporal bone showed a lytic aspect of the right temporal bone extending to the petrous apex and the petrous bone, sparing the otic capsule (Figure 1A). There was soft tissue opacification of the right mastoid air cells. Magnetic resonance imaging of the skull base with contrast was performed (Figure 1B). It showed a hyperintense T2 signal in the petrous apex and mastoid air cells. There was a suspected communication into the soft tissues of the right neck in the posterior triangle. Magnetic resonance imaging also showed signs of Chiari malformation type 1. After a skull base multidisciplinary discussion, the patient underwent a bone biopsy through a transmastoid approach. ### OUTPUT:

JAMA_FINAL282

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 60s with no significant medical history presented to the dermatology clinic for evaluation of a gray-white plaque on his soft palate. These findings developed over the prior week and did not improve after treatment with 3 days of oral cefuroxime. The patient reported no sore throat, dysphagia, hoarse voice, cough, dyspnea, nausea, vomiting, headache, fever, night sweats, weight loss, rash, or genital, rectal, or oral ulcers over the past 6 months. He was taking no regular daily medications, did not smoke cigarettes, and had no history of oral trauma. Over the prior 6 months, he reported sexual contact with 1 male partner. Physical examination revealed irregular gray-white ulcers with a surrounding erythema on the soft palate, uvula, and tonsils (Figure 1) and nontender bilateral submandibular lymphadenopathy. His tongue was of normal appearance, and he had no skin lesions or mucosal erosions in the anal or genital areas. ### OUTPUT:

Secondary syphilis

['Otolaryngology', 'Sexually Transmitted Infections', 'Dental Medicine', 'Dermatology', 'Infectious Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 60s with no significant medical history presented to the dermatology clinic for evaluation of a gray-white plaque on her soft palate. These findings developed over the prior week and did not improve after treatment with 3 days of oral cefuroxime. The patient reported no sore throat, dysphagia, hoarse voice, cough, dyspnea, nausea, vomiting, headache, fever, night sweats, weight loss, rash, or genital, rectal, or oral ulcers over the past 6 months. She was taking no regular daily medications, did not smoke cigarettes, and had no history of oral trauma. Over the prior 6 months, she reported sexual contact with 1 female partner. Physical examination revealed irregular gray-white ulcers with a surrounding erythema on the soft palate, uvula, and tonsils (Figure 1) and nontender bilateral submandibular lymphadenopathy. Her tongue was of normal appearance, and she had no skin lesions or mucosal erosions in the anal or genital areas. ### OUTPUT:

JAMA_FINAL283

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 12-year-old girl presented to the clinic with a 3-month history of intermittent stridor. Her symptoms were initially most prominent while playing sports and were suspected to be due to asthma or seasonal allergies. However, medical management with albuterol, intranasal fluticasone, and cetirizine failed to provide relief. More recently, the patient’s parents noted that she developed stridor while sleeping and while at rest, prompting the family to present for medical attention. Previous workup, including pulmonary function testing, was concerning for an upper airway obstructive process, for which she was referred to otolaryngology. In-office flexible videostroboscopy revealed a mass in the distal cervical trachea that appeared nearly obstructive. Chest radiography confirmed the presence of an approximately 1.5-cm, well-circumscribed soft tissue mass within the cervical trachea. Direct laryngoscopy and bronchoscopy were performed in the operating room under general anesthesia. This demonstrated an exophytic, pedunculated mass that emanated from the anterior wall of the cervical trachea (Figure 1A and B). The patient was intubated via Seldinger technique to bypass the mass, with a 4.0-mm cuffed endotracheal tube loaded over a 0-degree Hopkins endoscope (Figure 1C). With the airway secured, attention was turned to excision of the mass. Lidocaine, 1%, with epinephrine 1:100 000 was injected in a submucosal plane, and laryngeal scissors were used to excise the attachment of the mass from the tracheal wall. The mass was then resected en bloc and removed with laryngeal cupped forceps. The attachment site was then ablated with the Coblator (Figure 1D). ### OUTPUT:

Schwannoma

['Otolaryngology', 'Pediatrics', 'Head and Neck Surgery', 'Pulmonary Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 12-year-old boy presented to the clinic with a 3-month history of intermittent stridor. His symptoms were initially most prominent while playing sports and were suspected to be due to asthma or seasonal allergies. However, medical management with albuterol, intranasal fluticasone, and cetirizine failed to provide relief. More recently, the patient’s parents noted that he developed stridor while sleeping and while at rest, prompting the family to present for medical attention. Previous workup, including pulmonary function testing, was concerning for an upper airway obstructive process, for which he was referred to otolaryngology. In-office flexible videostroboscopy revealed a mass in the distal cervical trachea that appeared nearly obstructive. Chest radiography confirmed the presence of an approximately 1.5-cm, well-circumscribed soft tissue mass within the cervical trachea. Direct laryngoscopy and bronchoscopy were performed in the operating room under general anesthesia. This demonstrated an exophytic, pedunculated mass that emanated from the anterior wall of the cervical trachea (Figure 1A and B). The patient was intubated via Seldinger technique to bypass the mass, with a 4.0-mm cuffed endotracheal tube loaded over a 0-degree Hopkins endoscope (Figure 1C). With the airway secured, attention was turned to excision of the mass. Lidocaine, 1%, with epinephrine 1:100 000 was injected in a submucosal plane, and laryngeal scissors were used to excise the attachment of the mass from the tracheal wall. The mass was then resected en bloc and removed with laryngeal cupped forceps. The attachment site was then ablated with the Coblator (Figure 1D). ### OUTPUT:

JAMA_FINAL284

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-40s presented to the emergency department after a fall with head trauma. A head computed tomography showed a 0.9-cm left subdural hematoma with a mild left to right midline shift. Her ethanol level was 202 mg/dL (to convert to millimoles per liter, multiply by 0.2171); magnesium, 1.7 mg/dL (to convert to millimoles per liter, multiply by 0.4114); potassium, 4.4 mEq/L (to convert to millimoles per liter, multiply by 1); and ionized calcium, 4.6 mg/dL (to convert to millimoles per liter, multiply by 0.25). The patient developed cardiac arrest due to ventricular arrhythmias in the emergency department and was successfully resuscitated. Echocardiography demonstrated a left ventricular ejection fraction of 50% and no regional wall motion abnormalities. She subsequently underwent embolization of the middle meningeal artery. After embolization, however, a worsening rightward midline shift was discovered. As a result, on the 11th day of her hospitalization, she had a burr hole evacuation. During day 15 of admission, the patient had 3 episodes of torsade de pointes (TdP) while receiving 50 mg of metoprolol succinate daily, and her 12-lead electrocardiogram (ECG) is shown in Figure 1. ### OUTPUT:

T-wave alternans

['Cardiology', 'Emergency Medicine', 'Rhythm Disorders']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-40s presented to the emergency department after a fall with head trauma. A head computed tomography showed a 0.9-cm left subdural hematoma with a mild left to right midline shift. His ethanol level was 202 mg/dL (to convert to millimoles per liter, multiply by 0.2171); magnesium, 1.7 mg/dL (to convert to millimoles per liter, multiply by 0.4114); potassium, 4.4 mEq/L (to convert to millimoles per liter, multiply by 1); and ionized calcium, 4.6 mg/dL (to convert to millimoles per liter, multiply by 0.25). The patient developed cardiac arrest due to ventricular arrhythmias in the emergency department and was successfully resuscitated. Echocardiography demonstrated a left ventricular ejection fraction of 50% and no regional wall motion abnormalities. He subsequently underwent embolization of the middle meningeal artery. After embolization, however, a worsening rightward midline shift was discovered. As a result, on the 11th day of his hospitalization, he had a burr hole evacuation. During day 15 of admission, the patient had 3 episodes of torsade de pointes (TdP) while receiving 50 mg of metoprolol succinate daily, and his 12-lead electrocardiogram (ECG) is shown in Figure 1. ### OUTPUT:

JAMA_FINAL285

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A female patient in her late 40s presented with a 3-year history of nonhealing ulcers in her groin and axillae. These lesions started as itchy, weepy, reddish papules and plaques, which gradually progressed to form ulcers and were associated with pain and pus discharge. They did not heal completely after multiple courses of topical as well as systemic antibiotics, antifungals, and steroids. She frequently experienced scaling and greasiness on her scalp, which was treated with shampoos and topical steroids. She also complained of polyuria and polydipsia for the past 4 years. General examination revealed multiple mobile, firm, nonmatted, and nontender lymph nodes in cervical and inguinal region. On systemic examination, hepatomegaly (2 cm below the right costal margin) was seen. There was also bilateral enlargement of the parotid area, which was tender on palpation. Cutaneous examination revealed yellowish greasy scales on the scalp, suggestive of seborrheic dermatitis. Erythematous edematous papules were present over the retroauricular areas and the inframammary folds (Figure, A). On examination of external genitalia, deep ulcers were observed in the bilateral inguinal folds, resembling knife-cut ulcers (Figure, B). Similar lesions were present over the junction of labia majora and labia minora and were associated with yellowish pus discharge. A 3.5-mm punch biopsy specimen was obtained for histopathological examination from the edge of an ulcer on one of the groin folds (Figure, C and D). ### OUTPUT:

Langerhans cell histiocytosis

['Hematology', 'Oncology', 'Hematologic Cancer', 'Gynecology', "Women's Health"]

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A male patient in his late 40s presented with a 3-year history of nonhealing ulcers in his groin and axillae. These lesions started as itchy, weepy, reddish papules and plaques, which gradually progressed to form ulcers and were associated with pain and pus discharge. They did not heal completely after multiple courses of topical as well as systemic antibiotics, antifungals, and steroids. He frequently experienced scaling and greasiness on his scalp, which was treated with shampoos and topical steroids. He also complained of polyuria and polydipsia for the past 4 years. General examination revealed multiple mobile, firm, nonmatted, and nontender lymph nodes in cervical and inguinal region. On systemic examination, hepatomegaly (2 cm below the right costal margin) was seen. There was also bilateral enlargement of the parotid area, which was tender on palpation. Cutaneous examination revealed yellowish greasy scales on the scalp, suggestive of seborrheic dermatitis. Erythematous edematous papules were present over the retroauricular areas and the inframammary folds (Figure, A). On examination of external genitalia, deep ulcers were observed in the bilateral inguinal folds, resembling knife-cut ulcers (Figure, B). Similar lesions were present over the junction of the scrotum and were associated with yellowish pus discharge. A 3.5-mm punch biopsy specimen was obtained for histopathological examination from the edge of an ulcer on one of the groin folds (Figure, C and D). ### OUTPUT:

JAMA_FINAL286

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 48-year-old woman presented with 3 days of worsening right orbital swelling, eye pain, blurry vision, and 3 months of bilateral photophobia. She also reported bilateral rhinorrhea, congestion, and right frontal and temporal headaches. Active medical issues included hypertension, very poorly controlled type 2 diabetes, hyperlipidemia, tobacco use, and asthma. Her brother and father both had a history of chronic orbital swelling. Vital signs were unremarkable, and examination of the right eye showed moderate chemosis, injected conjunctiva, and periorbital edema. Both eyes were proptotic, right worse than left. She had normal bilateral extraocular movements, pupillary light reflexes, and gross vision. Computed tomography with contrast revealed bilateral ethmoid and frontal sinus opacification and right worse than left orbital fat stranding (Figure 1A). Magnetic resonance imaging with contrast demonstrated both enlargement and enhancement of bilateral extraocular muscles, especially the right superior rectus (Figure 1B). Initially she was started on antibiotic therapy. Right nasal biopsy, right endoscopic sinus surgery, and right anterior superior orbital tissue biopsy were performed. Intraoperatively, the sinus mucosa demonstrated only edema and mild secretions, but there was no necrosis or purulence. Both orbital and nasal cultures grew methicillin-resistant Staphylococcus aureus. Orbital biopsy showed nodular lymphoplasmacytic infiltrates without evidence of fungal infection or necrosis (Figure 1C). Further workup revealed elevated erythrocyte sedimentation rate, C-reactive protein, total IgG, and IgG4 levels and normal white blood cell count, thyroid-stimulating hormone, angiotensin-converting enzyme, lysozyme, antinuclear antibody, and antineutrophil cytoplasmic antibody (ANCA) levels. ### OUTPUT:

IgG4-related disease

['Ophthalmology', 'Otolaryngology', 'Rhinology and Sinus Disease', 'Orbit']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 48-year-old man presented with 3 days of worsening right orbital swelling, eye pain, blurry vision, and 3 months of bilateral photophobia. He also reported bilateral rhinorrhea, congestion, and right frontal and temporal headaches. Active medical issues included hypertension, very poorly controlled type 2 diabetes, hyperlipidemia, tobacco use, and asthma. His brother and father both had a history of chronic orbital swelling. Vital signs were unremarkable, and examination of the right eye showed moderate chemosis, injected conjunctiva, and periorbital edema. Both eyes were proptotic, right worse than left. He had normal bilateral extraocular movements, pupillary light reflexes, and gross vision. Computed tomography with contrast revealed bilateral ethmoid and frontal sinus opacification and right worse than left orbital fat stranding (Figure 1A). Magnetic resonance imaging with contrast demonstrated both enlargement and enhancement of bilateral extraocular muscles, especially the right superior rectus (Figure 1B). Initially he was started on antibiotic therapy. Right nasal biopsy, right endoscopic sinus surgery, and right anterior superior orbital tissue biopsy were performed. Intraoperatively, the sinus mucosa demonstrated only edema and mild secretions, but there was no necrosis or purulence. Both orbital and nasal cultures grew methicillin-resistant Staphylococcus aureus. Orbital biopsy showed nodular lymphoplasmacytic infiltrates without evidence of fungal infection or necrosis (Figure 1C). Further workup revealed elevated erythrocyte sedimentation rate, C-reactive protein, total IgG, and IgG4 levels and normal white blood cell count, thyroid-stimulating hormone, angiotensin-converting enzyme, lysozyme, antinuclear antibody, and antineutrophil cytoplasmic antibody (ANCA) levels. ### OUTPUT:

JAMA_FINAL287

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his 50s presented with bleeding wounds and nodules on the bilateral hips and forearms. He previously received failed systemic and radiation therapy for tumor stage mycosis fungoides (MF). He had received 11 courses of extended beam radiation therapy, including 3 courses of total skin irradiation of 24 to 30 Gy, and focal irradiation to the left posterior thigh and hip/buttock with 2.5/3 Gy to 12.5/24 Gy, respectively, and the right posterior thigh and hip with 2 Gy to 20 and 26 Gy, respectively. Seven years before this visit, he underwent a reduced-intensity, matched, unrelated donor, allogeneic hematopoietic stem cell transplant (HSCT). His post-transplant course was complicated by severe chronic graft vs host disease of the skin, eyes, and gut, for which he received systemic corticosteroid therapy, tacrolimus, methotrexate, and long-term extracorporeal photopheresis. Three years after the HSCT, he developed chronic ulcerations on the hips, back, and arms at the site of previously irradiated tumors, as well as multiple friable, hemorrhagic, and bleeding nodules on bilateral hips and his forearms while receiving treatment with corticosteroids and extracorporeal photopheresis. He underwent several debulking procedures and excision biopsies of the nodules, which revealed granulation tissue on histology. In this latest visit, physical examination revealed recurrent hemorrhagic and friable nodules on his left lateral hip and left lateral buttock (Figure 1). Similar nodules were noted on his right hip and forearm. The patient underwent repeated debulking and biopsy. He was also treated with micafungin, amphotericin B, levofloxacin, dapsone, acyclovir, pentamidine, penicillin VK, and posaconazole. Positron emission tomography (PET) computed tomography (CT) results did not show evidence of visceral or extracutaneous disease. ### OUTPUT:

Angiosarcoma

['Lymphomas', 'Skin Lymphomas', 'Dermatology', 'Hematology', 'Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her 50s presented with bleeding wounds and nodules on the bilateral hips and forearms. She previously received failed systemic and radiation therapy for tumor stage mycosis fungoides (MF). She had received 11 courses of extended beam radiation therapy, including 3 courses of total skin irradiation of 24 to 30 Gy, and focal irradiation to the left posterior thigh and hip/buttock with 2.5/3 Gy to 12.5/24 Gy, respectively, and the right posterior thigh and hip with 2 Gy to 20 and 26 Gy, respectively. Seven years before this visit, she underwent a reduced-intensity, matched, unrelated donor, allogeneic hematopoietic stem cell transplant (HSCT). Her post-transplant course was complicated by severe chronic graft vs host disease of the skin, eyes, and gut, for which she received systemic corticosteroid therapy, tacrolimus, methotrexate, and long-term extracorporeal photopheresis. Three years after the HSCT, she developed chronic ulcerations on the hips, back, and arms at the site of previously irradiated tumors, as well as multiple friable, hemorrhagic, and bleeding nodules on bilateral hips and her forearms while receiving treatment with corticosteroids and extracorporeal photopheresis. She underwent several debulking procedures and excision biopsies of the nodules, which revealed granulation tissue on histology. In this latest visit, physical examination revealed recurrent hemorrhagic and friable nodules on her left lateral hip and left lateral buttock (Figure 1). Similar nodules were noted on her right hip and forearm. The patient underwent repeated debulking and biopsy. She was also treated with micafungin, amphotericin B, levofloxacin, dapsone, acyclovir, pentamidine, penicillin VK, and posaconazole. Positron emission tomography (PET) computed tomography (CT) results did not show evidence of visceral or extracutaneous disease. ### OUTPUT:

JAMA_FINAL288

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his mid-50s with a medical history of nonspecific T-wave abnormalities on electrocardiogram (ECG) reported new-onset chest discomfort, diaphoresis, and shortness of breath that woke him from sleep. Emergency medical services found him to be in a wide complex tachycardia. He was administered a 150-mg bolus of intravenous amiodarone, which failed to terminate his arrhythmia. He ultimately required synchronized cardioversion with a biphasic direct current shock of 100 J. On arrival to the emergency department, his vital signs were stable. Serum electrolyte levels were within normal range and C-reactive protein was less than 6 mg/dL (to convert to milligrams per liter, multiply by 10). High-sensitivity troponin peaked at 1078 pg/mL. His initial 12-lead ECG is shown in Figure 1A. He continued in sinus rhythm with episodes of nonsustained ventricular tachycardia observed on telemetry, as shown in Figure 1B. Cardiac catheterization revealed patent coronary arteries. Cardiac magnetic resonance imaging was remarkable for a dilated right ventricle with moderately reduced systolic function and transmural late gadolinium enhancement with akinesis and dyskinesis involving the right ventricular (RV) free wall and outflow tract extending to the left ventricular (LV) anterior, septal, and apical segments. ### OUTPUT:

Cardiac sarcoidosis

['Rhythm Disorders', 'Cardiology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her mid-50s with a medical history of nonspecific T-wave abnormalities on electrocardiogram (ECG) reported new-onset chest discomfort, diaphoresis, and shortness of breath that woke her from sleep. Emergency medical services found her to be in a wide complex tachycardia. She was administered a 150-mg bolus of intravenous amiodarone, which failed to terminate her arrhythmia. She ultimately required synchronized cardioversion with a biphasic direct current shock of 100 J. On arrival to the emergency department, her vital signs were stable. Serum electrolyte levels were within normal range and C-reactive protein was less than 6 mg/dL (to convert to milligrams per liter, multiply by 10). High-sensitivity troponin peaked at 1078 pg/mL. Her initial 12-lead ECG is shown in Figure 1A. She continued in sinus rhythm with episodes of nonsustained ventricular tachycardia observed on telemetry, as shown in Figure 1B. Cardiac catheterization revealed patent coronary arteries. Cardiac magnetic resonance imaging was remarkable for a dilated right ventricle with moderately reduced systolic function and transmural late gadolinium enhancement with akinesis and dyskinesis involving the right ventricular (RV) free wall and outflow tract extending to the left ventricular (LV) anterior, septal, and apical segments. ### OUTPUT:

JAMA_FINAL291

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 68-year-old man with a history of keratoconus was referred for evaluation of a choroidal lesion in his left eye. He reported intermittent dull pain in his left eye for 1 month that improved with acetaminophen. His family history was significant for non-Hodgkin lymphoma (mother) and leukemia (mother and maternal grandfather). On examination, his best-corrected visual acuity was 20/25 OD and 20/200 OS, limited by keratoconus. Extraocular movements were full, there was no relative afferent pupillary defect, and intraocular pressures were 13 mm Hg OD and 11 mm Hg OS. There was no proptosis. Anterior segment examination demonstrated keratoconus with corneal scarring in both eyes and Descemet folds in the left eye. Both eyes had mixed cataract. There were no signs of anterior segment or vitreous inflammation. Ophthalmoscopic examination revealed an amelanotic area of choroidal thickening (confirmed by optical coherence tomography) overhanging the inferonasal margin of the optic disc with associated subretinal fluid and scattered areas of hyperpigmentation (Figure 1A). There was an additional, subtle amelanotic elevated lesion under the fovea. Fundus autofluorescence demonstrated hyperautofluorescence in a leopard-spotting pattern (Figure 1B). Indocyanine green angiography revealed hypocyanescent lesions inferonasal to the disc and at the fovea. ### OUTPUT:

Erdheim-Chester disease

['Hematology', 'Oncology', 'Hematologic Cancer', 'Ophthalmology', 'Ophthalmic Imaging']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 68-year-old woman with a history of keratoconus was referred for evaluation of a choroidal lesion in her left eye. She reported intermittent dull pain in her left eye for 1 month that improved with acetaminophen. Her family history was significant for non-Hodgkin lymphoma (mother) and leukemia (mother and maternal grandfather). On examination, her best-corrected visual acuity was 20/25 OD and 20/200 OS, limited by keratoconus. Extraocular movements were full, there was no relative afferent pupillary defect, and intraocular pressures were 13 mm Hg OD and 11 mm Hg OS. There was no proptosis. Anterior segment examination demonstrated keratoconus with corneal scarring in both eyes and Descemet folds in the left eye. Both eyes had mixed cataract. There were no signs of anterior segment or vitreous inflammation. Ophthalmoscopic examination revealed an amelanotic area of choroidal thickening (confirmed by optical coherence tomography) overhanging the inferonasal margin of the optic disc with associated subretinal fluid and scattered areas of hyperpigmentation (Figure 1A). There was an additional, subtle amelanotic elevated lesion under the fovea. Fundus autofluorescence demonstrated hyperautofluorescence in a leopard-spotting pattern (Figure 1B). Indocyanine green angiography revealed hypocyanescent lesions inferonasal to the disc and at the fovea. ### OUTPUT:

JAMA_FINAL292

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 19-year-old male presented for evaluation of painful lesions on the tongue that had been present for at least 3 months. He stated that the pain was exacerbated by spicy foods. He had initially presented to a primary care practitioner, was prescribed clotrimazole lozenges, and reported mild initial improvement followed by symptom progression. Subsequently, the practitioner referred the patient to an otolaryngologist. The patient denied any enlarged lymph nodes, fevers, fatigue, rash, weight loss, or abnormal gastrointestinal symptoms and had no noteworthy medical history. He reported mild alcohol consumption, denied any cigarette or illicit substance use, and endorsed engaging in oral and anal intercourse. A physical examination was notable for bilateral raised leukoplakia on the tongue; it was larger on the right side than the left and had a slightly hairy appearance. The lesion was tender to touch and could not be scraped off (Figure 1A). The lips and oral mucosa were without lesions, masses, or ulcers. The patient had no cervical lymphadenopathy. The findings of the physical examination were otherwise unremarkable. ### OUTPUT:

Secondary syphilis

['Otolaryngology', 'Dental Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 19-year-old female presented for evaluation of painful lesions on the tongue that had been present for at least 3 months. She stated that the pain was exacerbated by spicy foods. She had initially presented to a primary care practitioner, was prescribed clotrimazole lozenges, and reported mild initial improvement followed by symptom progression. Subsequently, the practitioner referred the patient to an otolaryngologist. The patient denied any enlarged lymph nodes, fevers, fatigue, rash, weight loss, or abnormal gastrointestinal symptoms and had no noteworthy medical history. She reported mild alcohol consumption, denied any cigarette or illicit substance use, and endorsed engaging in oral and anal intercourse. A physical examination was notable for bilateral raised leukoplakia on the tongue; it was larger on the right side than the left and had a slightly hairy appearance. The lesion was tender to touch and could not be scraped off (Figure 1A). The lips and oral mucosa were without lesions, masses, or ulcers. The patient had no cervical lymphadenopathy. The findings of the physical examination were otherwise unremarkable. ### OUTPUT:

JAMA_FINAL293

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 12-year-old boy presented with a 3-month history of nasal obstruction, progressive dysphonia, recurrent deep neck abscesses, and tender, bulky cervical lymphadenopathy. Computed tomography (CT) of the neck with contrast at his initial hospital admission was concerning for suppurative lymphadenitis. Despite incision and drainage, and intravenous ampicillin and sulbactam, his cervical lymphadenopathy persisted. Results of subsequent workup—including Haemophilus, tetanus, and pneumococcal antibody titers; QuantiFERON-TB Gold test; serum IgG, IgM, IgA, and IgE levels; absolute lymphocyte count; neutrophil phenotype and function; angiotensin-converting enzyme level; HLA-B27 test; and antinuclear antibody level—were within normal limits. Magnetic resonance imaging of the neck with gadolinium contrast demonstrated bilateral, bulky, enlarged cervical lymph nodes, as well as enhancing nodules in the left laryngeal ventricle (2.3 × 1.6 × 1.2 cm), right false vocal cord, and right tracheal wall (0.6 × 0.4 cm). Findings from nasal endoscopy, awake flexible laryngoscopy, and operative microlaryngoscopy revealed yellow submucosal masses in the left nasal cavity, left laryngeal ventricle, and right trachea, as well as left vocal cord paresis (Figure, A). Biopsies were taken of the tracheal, laryngeal, and nasal cavity masses, and an excisional biopsy was taken of a left cervical lymph node (Figure, B). Histopathologic examination revealed a prominent infiltrate of benign-appearing histiocytes with numerous forms showing emperipolesis and some nuclei showing distinct central nucleoli. Immunohistochemical staining in these cells was positive for S100 and negative for CD1a. ### OUTPUT:

Rosai-Dorfman disease

['Hematology', 'Pediatrics', 'Laryngology', 'Otolaryngology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A previously healthy 12-year-old girl presented with a 3-month history of nasal obstruction, progressive dysphonia, recurrent deep neck abscesses, and tender, bulky cervical lymphadenopathy. Computed tomography (CT) of the neck with contrast at her initial hospital admission was concerning for suppurative lymphadenitis. Despite incision and drainage, and intravenous ampicillin and sulbactam, her cervical lymphadenopathy persisted. Results of subsequent workup—including Haemophilus, tetanus, and pneumococcal antibody titers; QuantiFERON-TB Gold test; serum IgG, IgM, IgA, and IgE levels; absolute lymphocyte count; neutrophil phenotype and function; angiotensin-converting enzyme level; HLA-B27 test; and antinuclear antibody level—were within normal limits. Magnetic resonance imaging of the neck with gadolinium contrast demonstrated bilateral, bulky, enlarged cervical lymph nodes, as well as enhancing nodules in the left laryngeal ventricle (2.3 × 1.6 × 1.2 cm), right false vocal cord, and right tracheal wall (0.6 × 0.4 cm). Findings from nasal endoscopy, awake flexible laryngoscopy, and operative microlaryngoscopy revealed yellow submucosal masses in the left nasal cavity, left laryngeal ventricle, and right trachea, as well as left vocal cord paresis (Figure, A). Biopsies were taken of the tracheal, laryngeal, and nasal cavity masses, and an excisional biopsy was taken of a left cervical lymph node (Figure, B). Histopathologic examination revealed a prominent infiltrate of benign-appearing histiocytes with numerous forms showing emperipolesis and some nuclei showing distinct central nucleoli. Immunohistochemical staining in these cells was positive for S100 and negative for CD1a. ### OUTPUT:

JAMA_FINAL294

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old female patient with a history of hypercholesterolemia and anxiety was referred for progressive imbalance while walking and intense fear of falling for the past 14 years. The patient had become progressively disabled and had been using a wheelchair for 4 years prior to presentation. Neurological examination showed gaze-evoked horizontal nystagmus in both directions along with slow saccades and gaze restriction in both vertical and horizontal planes. There was ataxic dysarthria. Tone was normal in all 4 limbs but stretch reflexes were absent and plantar fascia were mute. Limb power was normal. Ataxia was seen on finger-to-nose and heel-knee-shin tests. Chorea was present in both legs. Ankle inversion with bilateral hammertoes was noted. Electromyography revealed sensory neuronopathy. On brain magnetic resonance imaging (MRI), diffuse cerebellar atrophy was noted along with T2 hyperintensities in bilateral middle cerebellar peduncles, cerebellar white matter, pons, and bilateral thalamus (Figure). Psychiatric treatment was commenced for her severe anxiety but did not relieve the fear of falling. ### OUTPUT:

Mitochondrial ataxia

['Neurogenetics', 'Neurology', 'Neuromuscular Diseases']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 55-year-old male patient with a history of hypercholesterolemia and anxiety was referred for progressive imbalance while walking and intense fear of falling for the past 14 years. The patient had become progressively disabled and had been using a wheelchair for 4 years prior to presentation. Neurological examination showed gaze-evoked horizontal nystagmus in both directions along with slow saccades and gaze restriction in both vertical and horizontal planes. There was ataxic dysarthria. Tone was normal in all 4 limbs but stretch reflexes were absent and plantar fascia were mute. Limb power was normal. Ataxia was seen on finger-to-nose and heel-knee-shin tests. Chorea was present in both legs. Ankle inversion with bilateral hammertoes was noted. Electromyography revealed sensory neuronopathy. On brain magnetic resonance imaging (MRI), diffuse cerebellar atrophy was noted along with T2 hyperintensities in bilateral middle cerebellar peduncles, cerebellar white matter, pons, and bilateral thalamus (Figure). Psychiatric treatment was commenced for his severe anxiety but did not relieve the fear of falling. ### OUTPUT:

JAMA_FINAL295

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A woman in her late 70s with a history of immunoglobulin A monoclonal gammopathy of unknown significance presented with a tender, draining lesion of the central face despite several courses of treatment with antibiotics (Figure, A). The patient lived in Southern California but had visited Kenya for an extended trip a few years prior. Review of systems was negative for fevers, night sweats, weight loss, headache, vision changes, respiratory distress, or arthralgias. On the left nasal dorsum and medial cheek, there was a 3 × 4 cm violaceous plaque with focal purulent drainage. Within several weeks, the lesion rapidly expanded into a vegetative, freely draining plaque covering the cheeks and glabella and approaching the medial canthi (Figure, B). Computed tomography revealed findings consistent with abscess that did not involve the orbits, sinuses, or bone. Chest radiography results were unremarkable. Punch biopsy specimens were obtained for histopathological analysis and tissue cultures (Figure, C). Tissue culture results at 2 weeks remained negative, and a QuantiFERON-TB Gold test result was negative. ### OUTPUT:

Pyoderma gangrenosum

['Dermatology', 'Hematology', 'Pathology and Laboratory Medicine', 'Rheumatology', 'Skin Infections']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A man in his late 70s with a history of immunoglobulin A monoclonal gammopathy of unknown significance presented with a tender, draining lesion of the central face despite several courses of treatment with antibiotics (Figure, A). The patient lived in Southern California but had visited Kenya for an extended trip a few years prior. Review of systems was negative for fevers, night sweats, weight loss, headache, vision changes, respiratory distress, or arthralgias. On the left nasal dorsum and medial cheek, there was a 3 × 4 cm violaceous plaque with focal purulent drainage. Within several weeks, the lesion rapidly expanded into a vegetative, freely draining plaque covering the cheeks and glabella and approaching the medial canthi (Figure, B). Computed tomography revealed findings consistent with abscess that did not involve the orbits, sinuses, or bone. Chest radiography results were unremarkable. Punch biopsy specimens were obtained for histopathological analysis and tissue cultures (Figure, C). Tissue culture results at 2 weeks remained negative, and a QuantiFERON-TB Gold test result was negative. ### OUTPUT:

JAMA_FINAL296

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive. ### OUTPUT:

Solitary fibrous tumor

['Otolaryngology', 'Salivary Gland Disorders', 'Dental Medicine', 'Facial Nerve', 'Facial Plastic Surgery']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An 81-year-old man presented with a 3-month history of a slow-growing mass in his left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive. ### OUTPUT:

JAMA_FINAL297

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C. ### OUTPUT:

Blastomycosis

['Fungal Infections', 'Infectious Diseases', 'Laryngology', 'Otolaryngology', 'Critical Care Medicine']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: An otherwise healthy woman in her 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. She denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. She was treated for asthma with inhaled steroids by her primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. Her neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C. ### OUTPUT:

JAMA_FINAL298

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 29-year-old Pakistani woman was referred to the otolaryngology clinic for increased postnasal drip, pharyngitis, odynophagia, cervicalgia, cervical lymphadenopathy, and right-sided otalgia that had persisted for more than a week. She was breastfeeding her 10-month-old, had no history of alcohol use, and had a remote history of hookah use. She was a Southern California native with travel history to Pakistan, Turkey, Jordan, Israel, Qatar, and Dubai 5 years prior to symptom onset. One month prior to onset, she drove from Los Angeles, California, to Houston, Texas. She denied recent unintentional weight loss, cough, fever, night sweats, chills, stridor, dyspnea, dysphonia, or rash. On examination, her vital signs were within normal limits, and physical examination revealed a small right tonsillolith, mild tonsillar erythema that was worse on the right side, and a mobile 2-cm, right level 2 lymph node that was slightly tender to palpation. Laboratory evaluation was notable for an elevated eosinophil count and positive Epstein-Barr immunoglobulin G. Her white blood cell count and mononucleosis spot test result were within normal parameters. Her symptoms persisted despite treatment with penicillin, azithromycin, and steroids from her primary physician and amoxicillin-clavulanate, sinus rinses, fluticasone propionate, and azelastine spray from an otolaryngologist to treat any contributing postnasal drainage and tonsillitis. Flexible transnasal videolaryngoscopy revealed a lesion on the laryngeal surface of the right epiglottis passing midline extending to the right aryepiglottic fold, but not involving the true vocal cords (Figure 1A). Given inconclusive office biopsy results, direct laryngoscopy with biopsy was performed, showing extensively inflamed squamous mucosa with ulceration, granulation tissue, pseudoepitheliomatous hyperplasia, and atypia (Figure 1B). ### OUTPUT:

Coccidioidomycosis

['Fungal Infections', 'Infectious Diseases', 'Laryngology', 'Otolaryngology', 'Swallowing and Dysphagia']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 29-year-old Pakistani man was referred to the otolaryngology clinic for increased postnasal drip, pharyngitis, odynophagia, cervicalgia, cervical lymphadenopathy, and right-sided otalgia that had persisted for more than a week. He was breastfeeding his 10-month-old, had no history of alcohol use, and had a remote history of hookah use. He was a Southern California native with travel history to Pakistan, Turkey, Jordan, Israel, Qatar, and Dubai 5 years prior to symptom onset. One month prior to onset, he drove from Los Angeles, California, to Houston, Texas. He denied recent unintentional weight loss, cough, fever, night sweats, chills, stridor, dyspnea, dysphonia, or rash. On examination, his vital signs were within normal limits, and physical examination revealed a small right tonsillolith, mild tonsillar erythema that was worse on the right side, and a mobile 2-cm, right level 2 lymph node that was slightly tender to palpation. Laboratory evaluation was notable for an elevated eosinophil count and positive Epstein-Barr immunoglobulin G. His white blood cell count and mononucleosis spot test result were within normal parameters. His symptoms persisted despite treatment with penicillin, azithromycin, and steroids from his primary physician and amoxicillin-clavulanate, sinus rinses, fluticasone propionate, and azelastine spray from an otolaryngologist to treat any contributing postnasal drainage and tonsillitis. Flexible transnasal videolaryngoscopy revealed a lesion on the laryngeal surface of the right epiglottis passing midline extending to the right aryepiglottic fold, but not involving the true vocal cords (Figure 1A). Given inconclusive office biopsy results, direct laryngoscopy with biopsy was performed, showing extensively inflamed squamous mucosa with ulceration, granulation tissue, pseudoepitheliomatous hyperplasia, and atypia (Figure 1B). ### OUTPUT:

JAMA_FINAL299

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old woman presented with horizontal binocular diplopia, right-sided ptosis, and a new headache that was progressive over 3 days. She reported difficulty opening her jaw, pain when chewing, and a 2.3-kg weight loss. The week prior, she experienced left-sided ptosis that persisted for 2 days and subsequently resolved. She denied vision changes, eye pain, scalp tenderness, and myalgias. Past medical history included schizophrenia, hypothyroidism, and supraventricular tachycardia. Her examination demonstrated normal visual acuity in both eyes. Pupils were equal, round, and reactive. There was right upper-eyelid ptosis. Extraocular motility demonstrated limitation of elevation and abduction bilaterally (Figure 1). Results of dilated fundus examination were normal, and the remainder of her neurologic examination results were normal. Her eye movements and ptosis did not change with fatiguability, rest, or an ice-pack test. Investigations revealed a C-reactive protein level of 292 mg/L (normal, <10 mg/L; to convert to milligrams per deciliter, divide by 10) and erythrocyte sedimentation rate of 93 mm/h (normal, <30 mm/h). A lumbar puncture demonstrated normal opening pressure, cell count, and glucose and protein levels. Magnetic resonance imaging with contrast of the brain demonstrated diffuse edema and enhancement of the scalp, skull base, neck, and paraspinal soft tissues, as well as T2 hyperintensity and enhancement of the extraocular muscles bilaterally. An additional test was obtained, and a diagnosis was made. ### OUTPUT:

Giant cell arteritis

['Neuro-ophthalmology', 'Neurology', 'Ophthalmology', 'Rheumatology', 'Geriatrics']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 75-year-old man presented with horizontal binocular diplopia, right-sided ptosis, and a new headache that was progressive over 3 days. He reported difficulty opening his jaw, pain when chewing, and a 2.3-kg weight loss. The week prior, he experienced left-sided ptosis that persisted for 2 days and subsequently resolved. He denied vision changes, eye pain, scalp tenderness, and myalgias. Past medical history included schizophrenia, hypothyroidism, and supraventricular tachycardia. His examination demonstrated normal visual acuity in both eyes. Pupils were equal, round, and reactive. There was right upper-eyelid ptosis. Extraocular motility demonstrated limitation of elevation and abduction bilaterally (Figure 1). Results of dilated fundus examination were normal, and the remainder of his neurologic examination results were normal. His eye movements and ptosis did not change with fatiguability, rest, or an ice-pack test. Investigations revealed a C-reactive protein level of 292 mg/L (normal, <10 mg/L; to convert to milligrams per deciliter, divide by 10) and erythrocyte sedimentation rate of 93 mm/h (normal, <30 mm/h). A lumbar puncture demonstrated normal opening pressure, cell count, and glucose and protein levels. Magnetic resonance imaging with contrast of the brain demonstrated diffuse edema and enhancement of the scalp, skull base, neck, and paraspinal soft tissues, as well as T2 hyperintensity and enhancement of the extraocular muscles bilaterally. An additional test was obtained, and a diagnosis was made. ### OUTPUT:

JAMA_FINAL300

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old African American man presented to the otolaryngology clinic with a several-month history of severe nasal congestion. Five years before this otolaryngology evaluation, the patient developed diffuse skin plaques with erythema and was subsequently diagnosed with hypopigmented cutaneous T-cell lymphoma (CTCL, mycosis fungoides type). The patient was treated with a regimen of narrowband UV-B phototherapy and triamcinolone cream, which he has continued for 4 years. Owing to significant worsening of his symptoms 4 months before his evaluation, a biopsy of his cutaneous lesions was performed to rule out progression of CTCL (Figure 1). Physical examination demonstrated large annular plaques with peripheral hyperpigmentation of the body. There were also confluent, indurated pink plaques with slightly raised edges along the forehead, malar eminence, and scalp. The nasal septum demonstrated an inverted V deformity with compromise of the keystone junction. Nasal passages were obstructed with thick mucus and synechiae formation, nearly obstructing the entire nasal passage bilaterally. ### OUTPUT:

Lepromatous leprosy

['Dermatology', 'Infectious Diseases', 'Otolaryngology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 66-year-old African American woman presented to the otolaryngology clinic with a several-month history of severe nasal congestion. Five years before this otolaryngology evaluation, the patient developed diffuse skin plaques with erythema and was subsequently diagnosed with hypopigmented cutaneous T-cell lymphoma (CTCL, mycosis fungoides type). The patient was treated with a regimen of narrowband UV-B phototherapy and triamcinolone cream, which she has continued for 4 years. Owing to significant worsening of her symptoms 4 months before her evaluation, a biopsy of her cutaneous lesions was performed to rule out progression of CTCL (Figure 1). Physical examination demonstrated large annular plaques with peripheral hyperpigmentation of the body. There were also confluent, indurated pink plaques with slightly raised edges along the forehead, malar eminence, and scalp. The nasal septum demonstrated an inverted V deformity with compromise of the keystone junction. Nasal passages were obstructed with thick mucus and synechiae formation, nearly obstructing the entire nasal passage bilaterally. ### OUTPUT:

JAMA_FINAL301

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 9-year-old boy was referred to a pediatric retina specialist for evaluation of changes in the peripheral retinal pigment epithelium. Ocular history included high hyperopia and amblyopia, and abnormal foveal contour was discovered when he was aged 3 years. Family history was noncontributory. Best-corrected visual acuity was 20/50 in the right eye and 20/30 in the left. Pupils were round and reactive to light, and intraocular pressure and anterior segment examination were within normal limits. Dilated fundus examination revealed blunted foveal reflexes and abnormal vasculature in the inferonasal quadrant of the right eye. Fluorescein angiography displayed symmetric bilateral circular areas of hypofluorescence around the macula and irregular fovea with no leakage (Figure 1A). Color fundus photography showed symmetric bilateral mottling of the retinal pigment epithelium in the periphery (Figure 1B). Spectral-domain optical coherence tomography on initial examination showed an abnormal foveal contour with loss of the foveal pit and intraretinal cystoid cavities within the inner nuclear layer. ### OUTPUT:

Congenital nanophthalmos

['Retinal Disorders', 'Pediatrics', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 9-year-old girl was referred to a pediatric retina specialist for evaluation of changes in the peripheral retinal pigment epithelium. Ocular history included high hyperopia and amblyopia, and abnormal foveal contour was discovered when she was aged 3 years. Family history was noncontributory. Best-corrected visual acuity was 20/50 in the right eye and 20/30 in the left. Pupils were round and reactive to light, and intraocular pressure and anterior segment examination were within normal limits. Dilated fundus examination revealed blunted foveal reflexes and abnormal vasculature in the inferonasal quadrant of the right eye. Fluorescein angiography displayed symmetric bilateral circular areas of hypofluorescence around the macula and irregular fovea with no leakage (Figure 1A). Color fundus photography showed symmetric bilateral mottling of the retinal pigment epithelium in the periphery (Figure 1B). Spectral-domain optical coherence tomography on initial examination showed an abnormal foveal contour with loss of the foveal pit and intraretinal cystoid cavities within the inner nuclear layer. ### OUTPUT:

JAMA_FINAL302

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-year-old boy presented with a vascular lesion involving the left orbit and face. He had a pink macule on his left cheek at birth, which became raised and discolored around age 3 to 4 weeks. He was diagnosed with a capillary hemangioma, and propranolol was started at age 1 month with progression despite dosage increases. Topical timolol was tried without improvement; oral prednisolone decreased the size of the lesion, but was poorly tolerated and discontinued. An ophthalmic evaluation at an outside hospital was concerning for amblyopia because of anisohypermetropia, greater on the left, and a left esotropia and hypertropia. A magnetic resonance image revealed an orbital mass surrounding the left lateral rectus muscle with mass effect on the globe and extension into the eyelid, pterygopalatine fossa, and cheek. Given the risk of amblyopia, the patient underwent 2 embolization and debulking procedures of the orbital and cheek components of the lesion, which were positive for glucose transporter 1 on pathology. However, the esotropia abruptly worsened after the second debulking. At age 3 years, he presented to the clinic with a persistent cheek and orbit lesion, dense amblyopia, large-angle monocular esotropia and hypertropia, and proptosis of the left eye. The left extraocular muscle showed inability to abduct past midline (Figure 1A). A repeated magnetic resonance image showed persistent orbital involvement causing medial displacement of the lateral rectus muscle and mass effect on the globe (Figure 1B). ### OUTPUT:

Infantile hemangioma

['Dermatology', 'Pediatrics', 'Cutaneous Vascular Malformations', 'External Eye Disease', 'Ophthalmology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 3-year-old girl presented with a vascular lesion involving the left orbit and face. She had a pink macule on her left cheek at birth, which became raised and discolored around age 3 to 4 weeks. She was diagnosed with a capillary hemangioma, and propranolol was started at age 1 month with progression despite dosage increases. Topical timolol was tried without improvement; oral prednisolone decreased the size of the lesion, but was poorly tolerated and discontinued. An ophthalmic evaluation at an outside hospital was concerning for amblyopia because of anisohypermetropia, greater on the left, and a left esotropia and hypertropia. A magnetic resonance image revealed an orbital mass surrounding the left lateral rectus muscle with mass effect on the globe and extension into the eyelid, pterygopalatine fossa, and cheek. Given the risk of amblyopia, the patient underwent 2 embolization and debulking procedures of the orbital and cheek components of the lesion, which were positive for glucose transporter 1 on pathology. However, the esotropia abruptly worsened after the second debulking. At age 3 years, she presented to the clinic with a persistent cheek and orbit lesion, dense amblyopia, large-angle monocular esotropia and hypertropia, and proptosis of the left eye. The left extraocular muscle showed inability to abduct past midline (Figure 1A). A repeated magnetic resonance image showed persistent orbital involvement causing medial displacement of the lateral rectus muscle and mass effect on the globe (Figure 1B). ### OUTPUT:

JAMA_FINAL303

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old elementary school principal with a history of cholecystectomy and appendectomy and no use of alcohol, illicit drugs, or cigarettes presented to the emergency department for the fourth time in 3 months with diffuse abdominal pain not associated with nausea, vomiting, diarrhea, constipation, hematochezia, weight loss, fever, or anorexia. On physical examination, the patient had normal vital signs, mild diffuse abdominal tenderness without rebound or guarding, and bluish pigmentation along his gingival margin (Figure, panel A). Blood testing showed alanine aminotransferase level 51 U/L (0.85 μkat/L; reference range, 7-23 U/L [0.12-0.38 μkat/L]), aspartate aminotransaminase 68 U/L (1.14 μkat/L; reference range, 13-30 U/L [0.22-0.50 μkat/L]), total bilirubin 3.2 mg/dL (54.73 μmol/L; reference range, 0.4-1.5 mg/dL [6.84-25.66 μmol/L]) and direct bilirubin 0.9 mg/dL (15.39 μmol/L; reference range, 0.0-0.4 mg/dL [0.0-6.84 μmol/L]). Hemoglobin level was 8.7 g/dL with a normal mean corpuscular volume, and ferritin level was 637.9 ng/mL (reference range, 39.9-465 ng/mL). Blood testing revealed normal lactate dehydrogenase, haptoglobin, iron, vitamin B12, folate, zinc, and copper levels, and results of urinalysis were normal. A peripheral blood smear demonstrated small, bluish-purple punctate inclusions in erythrocytes (Figure, panel B). Results of upper and lower endoscopy and abdominal-pelvic computed tomography performed within the past 3 months were unremarkable. ### OUTPUT:

Lead poisoning

['Complementary and Alternative Medicine', 'Gastroenterology', 'Hematology', 'Toxicology', 'Gastroenterology and Hepatology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 59-year-old elementary school principal with a history of cholecystectomy and appendectomy and no use of alcohol, illicit drugs, or cigarettes presented to the emergency department for the fourth time in 3 months with diffuse abdominal pain not associated with nausea, vomiting, diarrhea, constipation, hematochezia, weight loss, fever, or anorexia. On physical examination, the patient had normal vital signs, mild diffuse abdominal tenderness without rebound or guarding, and bluish pigmentation along her gingival margin (Figure, panel A). Blood testing showed alanine aminotransferase level 51 U/L (0.85 μkat/L; reference range, 7-23 U/L [0.12-0.38 μkat/L]), aspartate aminotransaminase 68 U/L (1.14 μkat/L; reference range, 13-30 U/L [0.22-0.50 μkat/L]), total bilirubin 3.2 mg/dL (54.73 μmol/L; reference range, 0.4-1.5 mg/dL [6.84-25.66 μmol/L]) and direct bilirubin 0.9 mg/dL (15.39 μmol/L; reference range, 0.0-0.4 mg/dL [0.0-6.84 μmol/L]). Hemoglobin level was 8.7 g/dL with a normal mean corpuscular volume, and ferritin level was 637.9 ng/mL (reference range, 39.9-465 ng/mL). Blood testing revealed normal lactate dehydrogenase, haptoglobin, iron, vitamin B12, folate, zinc, and copper levels, and results of urinalysis were normal. A peripheral blood smear demonstrated small, bluish-purple punctate inclusions in erythrocytes (Figure, panel B). Results of upper and lower endoscopy and abdominal-pelvic computed tomography performed within the past 3 months were unremarkable. ### OUTPUT:

JAMA_FINAL304

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 50-year-old man was referred for ophthalmoplegia that developed immediately after an 8.5-hour robotic cystectomy for small cell cancer of the bladder. After recovering from anesthesia in the postanesthesia care unit, he experienced headache, facial numbness, inability to open both his eyes, and inability to move both eyes in any direction. He had a known enhancing central skull base lesion in sella turcica with compression of the optic chiasm and mild mass effect on the pons that was felt to be a pituitary macroadenoma (Figure). His baseline examination before the cystectomy showed visual acuity of 20/20 OU with intact extraocular movements and unremarkable confrontational fields, although a mild bitemporal hemianopia was seen on automated visual fields. ### OUTPUT:

Pituitary apoplexy

['Neurology', 'Oncology', 'Ophthalmology', 'Surgery', 'Surgical Oncology']

Develop a 10-Step differential diagnosis, for each step, give only one differential diagnosis with only the disease name at current step, do not provide repeated hypotheses or diagnoses that appear in previous steps. Rerank all 10 differential diagnosis using all patient information and test results. Let’s think step by step. ### INPUT: A 50-year-old woman was referred for ophthalmoplegia that developed immediately after an 8.5-hour robotic cystectomy for small cell cancer of the bladder. After recovering from anesthesia in the postanesthesia care unit, she experienced headache, facial numbness, inability to open both her eyes, and inability to move both eyes in any direction. She had a known enhancing central skull base lesion in sella turcica with compression of the optic chiasm and mild mass effect on the pons that was felt to be a pituitary macroadenoma (Figure). Her baseline examination before the cystectomy showed visual acuity of 20/20 OU with intact extraocular movements and unremarkable confrontational fields, although a mild bitemporal hemianopia was seen on automated visual fields. ### OUTPUT: