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Surgery_Schwartz_10802 | Surgery_Schwartz | subclinical hypothyroidism and increased antithy-roid antibody levels should be treated because they will sub-sequently develop hypothyroidism. Patients who present with myxedema coma may require initial emergency treatment with large doses of IV T4 (300 to 400 μg), with careful monitoring in an intensive care unit setting.9Thyroiditis. Thyroiditis usually is classified into acute, sub-acute, and chronic forms, each associated with a distinct clinical presentation and histology.Acute (Suppurative) Thyroiditis The thyroid gland is inherently resistant to infection due to its extensive blood and lymphatic supply, high iodide content, and fibrous capsule. However, infectious agents can seed it (a) via the hematoge-nous or lymphatic route, (b) via direct spread from persistent pyriform sinus fistulae or thyroglossal duct cysts, (c) as a result of penetrating trauma to the thyroid gland, or (d) due to immu-nosuppression. Streptococcus and anaerobes account for about 70% of cases; however, | Surgery_Schwartz. subclinical hypothyroidism and increased antithy-roid antibody levels should be treated because they will sub-sequently develop hypothyroidism. Patients who present with myxedema coma may require initial emergency treatment with large doses of IV T4 (300 to 400 μg), with careful monitoring in an intensive care unit setting.9Thyroiditis. Thyroiditis usually is classified into acute, sub-acute, and chronic forms, each associated with a distinct clinical presentation and histology.Acute (Suppurative) Thyroiditis The thyroid gland is inherently resistant to infection due to its extensive blood and lymphatic supply, high iodide content, and fibrous capsule. However, infectious agents can seed it (a) via the hematoge-nous or lymphatic route, (b) via direct spread from persistent pyriform sinus fistulae or thyroglossal duct cysts, (c) as a result of penetrating trauma to the thyroid gland, or (d) due to immu-nosuppression. Streptococcus and anaerobes account for about 70% of cases; however, |
Surgery_Schwartz_10803 | Surgery_Schwartz | fistulae or thyroglossal duct cysts, (c) as a result of penetrating trauma to the thyroid gland, or (d) due to immu-nosuppression. Streptococcus and anaerobes account for about 70% of cases; however, other species also have been cultured.10 Acute suppurative thyroiditis is more common in children and often is preceded by an upper respiratory tract infection or otitis media. It is characterized by severe neck pain radiating to the jaws or ear, fever, chills, odynophagia, and dysphonia. Compli-cations such as systemic sepsis, tracheal or esophageal rupture, jugular vein thrombosis, laryngeal chondritis, and perichondritis or sympathetic trunk paralysis may also occur.The diagnosis is established by leukocytosis on blood tests and FNAB for Gram’s stain, culture, and cytology. CT scans may help to delineate the extent of infection and identify abscesses. A persistent pyriform sinus fistula should always be suspected in children with recurrent acute thyroiditis. The sensitivity of | Surgery_Schwartz. fistulae or thyroglossal duct cysts, (c) as a result of penetrating trauma to the thyroid gland, or (d) due to immu-nosuppression. Streptococcus and anaerobes account for about 70% of cases; however, other species also have been cultured.10 Acute suppurative thyroiditis is more common in children and often is preceded by an upper respiratory tract infection or otitis media. It is characterized by severe neck pain radiating to the jaws or ear, fever, chills, odynophagia, and dysphonia. Compli-cations such as systemic sepsis, tracheal or esophageal rupture, jugular vein thrombosis, laryngeal chondritis, and perichondritis or sympathetic trunk paralysis may also occur.The diagnosis is established by leukocytosis on blood tests and FNAB for Gram’s stain, culture, and cytology. CT scans may help to delineate the extent of infection and identify abscesses. A persistent pyriform sinus fistula should always be suspected in children with recurrent acute thyroiditis. The sensitivity of |
Surgery_Schwartz_10804 | Surgery_Schwartz | may help to delineate the extent of infection and identify abscesses. A persistent pyriform sinus fistula should always be suspected in children with recurrent acute thyroiditis. The sensitivity of identification of fistulae in the acute setting is lowest for barium esophagography (50%) and best for direct endoscopy (100%), with CT scans being intermediate (80%). Both barium esopha-gogram and CT scans have improved sensitivity once the acute inflammation has resolved (100% and 83%, respectively), with CT being better at defining the accurate anatomic pathway and its relationship to the thyroid gland.11 Treatment consists of parenteral antibiotics and drainage of abscesses. Thyroidec-tomy may be needed for persistent abscesses or failure of open drainage. Patients with pyriform sinus fistulae require complete resection of the sinus tract, including the area of the thyroid where the tract terminates, to prevent recurrence. Transnasal flexible fiberoptic laryngoscopy is being | Surgery_Schwartz. may help to delineate the extent of infection and identify abscesses. A persistent pyriform sinus fistula should always be suspected in children with recurrent acute thyroiditis. The sensitivity of identification of fistulae in the acute setting is lowest for barium esophagography (50%) and best for direct endoscopy (100%), with CT scans being intermediate (80%). Both barium esopha-gogram and CT scans have improved sensitivity once the acute inflammation has resolved (100% and 83%, respectively), with CT being better at defining the accurate anatomic pathway and its relationship to the thyroid gland.11 Treatment consists of parenteral antibiotics and drainage of abscesses. Thyroidec-tomy may be needed for persistent abscesses or failure of open drainage. Patients with pyriform sinus fistulae require complete resection of the sinus tract, including the area of the thyroid where the tract terminates, to prevent recurrence. Transnasal flexible fiberoptic laryngoscopy is being |
Surgery_Schwartz_10805 | Surgery_Schwartz | sinus fistulae require complete resection of the sinus tract, including the area of the thyroid where the tract terminates, to prevent recurrence. Transnasal flexible fiberoptic laryngoscopy is being increasingly used to identify the internal opening of the pyriform sinus tract and may also allow electrocauterization of the tract, and success rates similar to open surgery have been reported.Subacute Thyroiditis Subacute thyroiditis can occur in the painful or painless forms. Although the exact etiology is not known, painful thyroiditis is thought to be viral in origin or result from a postviral inflammatory response. Genetic pre-disposition may also play a role, as manifested by its strong association with the HLA-B35 haplotype. One model of patho-genesis suggests that viral or thyroid antigens, when presented by macrophages in the context of HLA-B35, stimulate cytotoxic T lymphocytes and damage thyroid follicular cells.Painful thyroiditis most commonly occurs in 30to 40-year-old | Surgery_Schwartz. sinus fistulae require complete resection of the sinus tract, including the area of the thyroid where the tract terminates, to prevent recurrence. Transnasal flexible fiberoptic laryngoscopy is being increasingly used to identify the internal opening of the pyriform sinus tract and may also allow electrocauterization of the tract, and success rates similar to open surgery have been reported.Subacute Thyroiditis Subacute thyroiditis can occur in the painful or painless forms. Although the exact etiology is not known, painful thyroiditis is thought to be viral in origin or result from a postviral inflammatory response. Genetic pre-disposition may also play a role, as manifested by its strong association with the HLA-B35 haplotype. One model of patho-genesis suggests that viral or thyroid antigens, when presented by macrophages in the context of HLA-B35, stimulate cytotoxic T lymphocytes and damage thyroid follicular cells.Painful thyroiditis most commonly occurs in 30to 40-year-old |
Surgery_Schwartz_10806 | Surgery_Schwartz | antigens, when presented by macrophages in the context of HLA-B35, stimulate cytotoxic T lymphocytes and damage thyroid follicular cells.Painful thyroiditis most commonly occurs in 30to 40-year-old women and is characterized by the sudden or grad-ual onset of neck pain, which may radiate toward the mandible or ear. History of a preceding upper respiratory tract infection often can be elicited. The gland is enlarged, exquisitely ten-der, and firm. The disorder classically progresses through four stages. An initial hyperthyroid phase, due to release of thyroid hormone, is followed by a second, euthyroid phase. The third phase, hypothyroidism, occurs in about 20% to 30% of patients and is followed by resolution and return to the euthyroid state in >90% of patients. A few patients develop recurrent disease.In the early stages of the disease, TSH is decreased, and Tg, T4, and T3 levels are elevated due to the release of pre-formed thyroid hormone from destroyed follicles. The erythro-cyte | Surgery_Schwartz. antigens, when presented by macrophages in the context of HLA-B35, stimulate cytotoxic T lymphocytes and damage thyroid follicular cells.Painful thyroiditis most commonly occurs in 30to 40-year-old women and is characterized by the sudden or grad-ual onset of neck pain, which may radiate toward the mandible or ear. History of a preceding upper respiratory tract infection often can be elicited. The gland is enlarged, exquisitely ten-der, and firm. The disorder classically progresses through four stages. An initial hyperthyroid phase, due to release of thyroid hormone, is followed by a second, euthyroid phase. The third phase, hypothyroidism, occurs in about 20% to 30% of patients and is followed by resolution and return to the euthyroid state in >90% of patients. A few patients develop recurrent disease.In the early stages of the disease, TSH is decreased, and Tg, T4, and T3 levels are elevated due to the release of pre-formed thyroid hormone from destroyed follicles. The erythro-cyte |
Surgery_Schwartz_10807 | Surgery_Schwartz | disease.In the early stages of the disease, TSH is decreased, and Tg, T4, and T3 levels are elevated due to the release of pre-formed thyroid hormone from destroyed follicles. The erythro-cyte sedimentation rate is typically >100 mm/h. RAIU also is decreased (<2% at 24 hours), even in euthyroid patients, due to the release of thyroid hormones from destruction of the thyroid parenchyma. Painful thyroiditis is self-limited, and therefore, treatment is primarily symptomatic. Aspirin and other nonste-roidal anti-inflammatory drugs are used for pain relief, but ste-roids may be indicated in more severe cases. Short-term thyroid replacement may be needed and may shorten the duration of symptoms. Thyroidectomy is reserved for the rare patient who has a prolonged course not responsive to medical measures or for recurrent disease.Painless thyroiditis is considered to be autoimmune in ori-gin and may occur sporadically or in the postpartum period; the latter typically occurs at about 6 weeks | Surgery_Schwartz. disease.In the early stages of the disease, TSH is decreased, and Tg, T4, and T3 levels are elevated due to the release of pre-formed thyroid hormone from destroyed follicles. The erythro-cyte sedimentation rate is typically >100 mm/h. RAIU also is decreased (<2% at 24 hours), even in euthyroid patients, due to the release of thyroid hormones from destruction of the thyroid parenchyma. Painful thyroiditis is self-limited, and therefore, treatment is primarily symptomatic. Aspirin and other nonste-roidal anti-inflammatory drugs are used for pain relief, but ste-roids may be indicated in more severe cases. Short-term thyroid replacement may be needed and may shorten the duration of symptoms. Thyroidectomy is reserved for the rare patient who has a prolonged course not responsive to medical measures or for recurrent disease.Painless thyroiditis is considered to be autoimmune in ori-gin and may occur sporadically or in the postpartum period; the latter typically occurs at about 6 weeks |
Surgery_Schwartz_10808 | Surgery_Schwartz | measures or for recurrent disease.Painless thyroiditis is considered to be autoimmune in ori-gin and may occur sporadically or in the postpartum period; the latter typically occurs at about 6 weeks after delivery in women with high TPO antibody titers in early pregnancy. This timing is thought to coincide with a decrease in the normal immune tolerance of pregnancy and consequent rebound elevation of antibody titers.Painless thyroiditis also is more common in women and usually occurs between 30 and 60 years of age. Physical exami-nation demonstrates a normal sized or minimally enlarged, slightly firm, nontender gland. Laboratory tests and RAIU are similar to those in painful thyroiditis, except for a normal erythrocyte sedimentation rate. The clinical course also paral-lels painful thyroiditis. Patients with symptoms may require β-blockers and thyroid hormone replacement. Thyroidectomy or RAI ablation is only indicated for the rare patient with recur-rent, disabling episodes of | Surgery_Schwartz. measures or for recurrent disease.Painless thyroiditis is considered to be autoimmune in ori-gin and may occur sporadically or in the postpartum period; the latter typically occurs at about 6 weeks after delivery in women with high TPO antibody titers in early pregnancy. This timing is thought to coincide with a decrease in the normal immune tolerance of pregnancy and consequent rebound elevation of antibody titers.Painless thyroiditis also is more common in women and usually occurs between 30 and 60 years of age. Physical exami-nation demonstrates a normal sized or minimally enlarged, slightly firm, nontender gland. Laboratory tests and RAIU are similar to those in painful thyroiditis, except for a normal erythrocyte sedimentation rate. The clinical course also paral-lels painful thyroiditis. Patients with symptoms may require β-blockers and thyroid hormone replacement. Thyroidectomy or RAI ablation is only indicated for the rare patient with recur-rent, disabling episodes of |
Surgery_Schwartz_10809 | Surgery_Schwartz | thyroiditis. Patients with symptoms may require β-blockers and thyroid hormone replacement. Thyroidectomy or RAI ablation is only indicated for the rare patient with recur-rent, disabling episodes of thyroiditis.Brunicardi_Ch38_p1625-p1704.indd 163901/03/19 11:20 AM 1640SPECIFIC CONSIDERATIONSPART IIChronic Thyroiditis Lymphocytic (Hashimoto’s) Thyroiditis. Lymphocytic thy-roiditis was first described by Hashimoto in 1912 as struma lymphomatosa—a transformation of thyroid tissue to lymphoid tissue. It is the most common inflammatory disorder of the thy-roid and the leading cause of hypothyroidism today.Etiology, Pathogenesis, and Pathology Hashimoto’s thyroid-itis is an autoimmune process that is thought to be initiated by the activation of CD4+ T (helper) lymphocytes with specificity for thyroid antigens. Once activated, T cells can recruit cyto-toxic CD8+ T cells to the thyroid. Hypothyroidism results not only from the destruction of thyrocytes by cytotoxic T cells but also by | Surgery_Schwartz. thyroiditis. Patients with symptoms may require β-blockers and thyroid hormone replacement. Thyroidectomy or RAI ablation is only indicated for the rare patient with recur-rent, disabling episodes of thyroiditis.Brunicardi_Ch38_p1625-p1704.indd 163901/03/19 11:20 AM 1640SPECIFIC CONSIDERATIONSPART IIChronic Thyroiditis Lymphocytic (Hashimoto’s) Thyroiditis. Lymphocytic thy-roiditis was first described by Hashimoto in 1912 as struma lymphomatosa—a transformation of thyroid tissue to lymphoid tissue. It is the most common inflammatory disorder of the thy-roid and the leading cause of hypothyroidism today.Etiology, Pathogenesis, and Pathology Hashimoto’s thyroid-itis is an autoimmune process that is thought to be initiated by the activation of CD4+ T (helper) lymphocytes with specificity for thyroid antigens. Once activated, T cells can recruit cyto-toxic CD8+ T cells to the thyroid. Hypothyroidism results not only from the destruction of thyrocytes by cytotoxic T cells but also by |
Surgery_Schwartz_10810 | Surgery_Schwartz | for thyroid antigens. Once activated, T cells can recruit cyto-toxic CD8+ T cells to the thyroid. Hypothyroidism results not only from the destruction of thyrocytes by cytotoxic T cells but also by autoantibodies, which lead to complement fixation and killing by natural killer cells or block the TSH-R. Antibod-ies are directed against three main antigens—Tg (60%), TPO (95%), and TSH-R (60%)—and, less commonly, the sodium/iodine symporter (25%). Apoptosis (programmed cell death) also has been implicated in the pathogenesis of Hashimoto’s thyroiditis. Chronic thyroiditis also has been associated with increased intake of iodine and administration of medications such as interferon-α, lithium, and amiodarone. Support for an inherited predisposition includes an increased incidence of thyroid autoantibodies in first-degree relatives of patients with Hashimoto’s thyroiditis compared to controls and the occur-rence of the autoantibodies and hypothyroidism in patients with specific chromosomal | Surgery_Schwartz. for thyroid antigens. Once activated, T cells can recruit cyto-toxic CD8+ T cells to the thyroid. Hypothyroidism results not only from the destruction of thyrocytes by cytotoxic T cells but also by autoantibodies, which lead to complement fixation and killing by natural killer cells or block the TSH-R. Antibod-ies are directed against three main antigens—Tg (60%), TPO (95%), and TSH-R (60%)—and, less commonly, the sodium/iodine symporter (25%). Apoptosis (programmed cell death) also has been implicated in the pathogenesis of Hashimoto’s thyroiditis. Chronic thyroiditis also has been associated with increased intake of iodine and administration of medications such as interferon-α, lithium, and amiodarone. Support for an inherited predisposition includes an increased incidence of thyroid autoantibodies in first-degree relatives of patients with Hashimoto’s thyroiditis compared to controls and the occur-rence of the autoantibodies and hypothyroidism in patients with specific chromosomal |
Surgery_Schwartz_10811 | Surgery_Schwartz | in first-degree relatives of patients with Hashimoto’s thyroiditis compared to controls and the occur-rence of the autoantibodies and hypothyroidism in patients with specific chromosomal abnormalities such as Turner’s syn-drome and Down syndrome. Associations with HLA-B8, DR3, and DR5 haplotypes of the major histocompatibility complex also have been described. Alterations in CTLA4 have also been shown to increase the risk of developing Hashimoto’s thyroid-itis. Other associated genes include various cytokine genes, GITR (glucocorticoid-induced tumor necrosis factor-receptor) and STAT 3; however, these need further confirmatory studies.11On gross examination, the thyroid gland is usually mildly enlarged throughout and has a pale, gray-tan cut surface that is granular, nodular, and firm. On microscopic examination, the gland is diffusely infiltrated by small lymphocytes and plasma cells and occasionally shows well-developed germinal centers. Thyroid follicles are smaller than normal | Surgery_Schwartz. in first-degree relatives of patients with Hashimoto’s thyroiditis compared to controls and the occur-rence of the autoantibodies and hypothyroidism in patients with specific chromosomal abnormalities such as Turner’s syn-drome and Down syndrome. Associations with HLA-B8, DR3, and DR5 haplotypes of the major histocompatibility complex also have been described. Alterations in CTLA4 have also been shown to increase the risk of developing Hashimoto’s thyroid-itis. Other associated genes include various cytokine genes, GITR (glucocorticoid-induced tumor necrosis factor-receptor) and STAT 3; however, these need further confirmatory studies.11On gross examination, the thyroid gland is usually mildly enlarged throughout and has a pale, gray-tan cut surface that is granular, nodular, and firm. On microscopic examination, the gland is diffusely infiltrated by small lymphocytes and plasma cells and occasionally shows well-developed germinal centers. Thyroid follicles are smaller than normal |
Surgery_Schwartz_10812 | Surgery_Schwartz | On microscopic examination, the gland is diffusely infiltrated by small lymphocytes and plasma cells and occasionally shows well-developed germinal centers. Thyroid follicles are smaller than normal with reduced amounts of colloid and increased interstitial connective tissue. The fol-licles are lined by Hürthle or Askanazy cells, which are charac-terized by abundant eosinophilic, granular cytoplasm.Clinical Presentation Hashimoto’s thyroiditis is also more common in women (male-to-female ratio is 1:10 to 20) between the ages of 30 and 50 years old. The most common presenta-tion is that of a minimally or moderately enlarged firm granular gland discovered on routine physical examination or the aware-ness of a painless anterior neck mass, although 20% of patients present with hypothyroidism, and 5% present with hyperthy-roidism (Hashitoxicosis). In classic goitrous Hashimoto’s thy-roiditis, physical examination reveals a diffusely enlarged, firm gland, which also is lobulated. An | Surgery_Schwartz. On microscopic examination, the gland is diffusely infiltrated by small lymphocytes and plasma cells and occasionally shows well-developed germinal centers. Thyroid follicles are smaller than normal with reduced amounts of colloid and increased interstitial connective tissue. The fol-licles are lined by Hürthle or Askanazy cells, which are charac-terized by abundant eosinophilic, granular cytoplasm.Clinical Presentation Hashimoto’s thyroiditis is also more common in women (male-to-female ratio is 1:10 to 20) between the ages of 30 and 50 years old. The most common presenta-tion is that of a minimally or moderately enlarged firm granular gland discovered on routine physical examination or the aware-ness of a painless anterior neck mass, although 20% of patients present with hypothyroidism, and 5% present with hyperthy-roidism (Hashitoxicosis). In classic goitrous Hashimoto’s thy-roiditis, physical examination reveals a diffusely enlarged, firm gland, which also is lobulated. An |
Surgery_Schwartz_10813 | Surgery_Schwartz | and 5% present with hyperthy-roidism (Hashitoxicosis). In classic goitrous Hashimoto’s thy-roiditis, physical examination reveals a diffusely enlarged, firm gland, which also is lobulated. An enlarged pyramidal lobe often is palpable.Diagnostic Studies When Hashimoto’s thyroiditis is suspected clinically, an elevated TSH and the presence of thyroid autoan-tibodies usually confirm the diagnosis. FNAB with ultrasound guidance is indicated in patients who present with a solitary suspicious nodule or a rapidly enlarging goiter. Thyroid lym-phoma is a rare but well-recognized, ominous complication of chronic autoimmune thyroiditis and has a prevalence 80 times higher than expected frequency in this population than in a control population without thyroiditis. Studies of clonal simi-larity indicate that lymphoma may, in fact, evolve from Hashi-moto’s thyroiditis.12Treatment Thyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining nor-mal | Surgery_Schwartz. and 5% present with hyperthy-roidism (Hashitoxicosis). In classic goitrous Hashimoto’s thy-roiditis, physical examination reveals a diffusely enlarged, firm gland, which also is lobulated. An enlarged pyramidal lobe often is palpable.Diagnostic Studies When Hashimoto’s thyroiditis is suspected clinically, an elevated TSH and the presence of thyroid autoan-tibodies usually confirm the diagnosis. FNAB with ultrasound guidance is indicated in patients who present with a solitary suspicious nodule or a rapidly enlarging goiter. Thyroid lym-phoma is a rare but well-recognized, ominous complication of chronic autoimmune thyroiditis and has a prevalence 80 times higher than expected frequency in this population than in a control population without thyroiditis. Studies of clonal simi-larity indicate that lymphoma may, in fact, evolve from Hashi-moto’s thyroiditis.12Treatment Thyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining nor-mal |
Surgery_Schwartz_10814 | Surgery_Schwartz | that lymphoma may, in fact, evolve from Hashi-moto’s thyroiditis.12Treatment Thyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining nor-mal TSH levels. The management of patients with subclinical hypothyroidism (normal T4 and elevated TSH) is controversial. A systematic review of cohort studies showed that in ageand sex-adjusted analyses, subclinical hypothyroidism is associated with a hazard ratio (HR) for coronary heart disease events of 1.89 (95% confidence interval [CI], 1.28 to 2.80; P <.001) and coronary heart disease mortality of 1.58 (95% CI, 1.10 to 2.27; P = .005) for a TSH level of 10 to 19.9 mIU/L.13 The data for TSH levels of 5 to 10 mIU/L were less convincing. An evalu-ation of the 12 randomized controlled trials in this area only showed a trend toward improvement of some lipid parameters, and none of the included trials evaluated overall mortality or car-diac morbidity. For this reason, levothyroxine is recommended | Surgery_Schwartz. that lymphoma may, in fact, evolve from Hashi-moto’s thyroiditis.12Treatment Thyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining nor-mal TSH levels. The management of patients with subclinical hypothyroidism (normal T4 and elevated TSH) is controversial. A systematic review of cohort studies showed that in ageand sex-adjusted analyses, subclinical hypothyroidism is associated with a hazard ratio (HR) for coronary heart disease events of 1.89 (95% confidence interval [CI], 1.28 to 2.80; P <.001) and coronary heart disease mortality of 1.58 (95% CI, 1.10 to 2.27; P = .005) for a TSH level of 10 to 19.9 mIU/L.13 The data for TSH levels of 5 to 10 mIU/L were less convincing. An evalu-ation of the 12 randomized controlled trials in this area only showed a trend toward improvement of some lipid parameters, and none of the included trials evaluated overall mortality or car-diac morbidity. For this reason, levothyroxine is recommended |
Surgery_Schwartz_10815 | Surgery_Schwartz | area only showed a trend toward improvement of some lipid parameters, and none of the included trials evaluated overall mortality or car-diac morbidity. For this reason, levothyroxine is recommended for all patients with TSH levels >10 μIU/mL and patients with levels of 5 to 10 μIU/mL in the presence of a goiter or anti-TPO antibodies. Treatment is also advised especially for middle-aged patients with cardiovascular risk factors such as hyperlipidemia or hypertension and in pregnant patients. Surgery may occa-sionally be indicated for suspicion of malignancy or for goiters causing compressive symptoms or cosmetic deformity.Riedel’s Thyroiditis Riedel’s thyroiditis is a rare variant of thyroiditis also known as Riedel’s struma or invasive fibrous thyroiditis that is characterized by the replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues. The etiology of this disorder is contro-versial, and it has been reported to occur in | Surgery_Schwartz. area only showed a trend toward improvement of some lipid parameters, and none of the included trials evaluated overall mortality or car-diac morbidity. For this reason, levothyroxine is recommended for all patients with TSH levels >10 μIU/mL and patients with levels of 5 to 10 μIU/mL in the presence of a goiter or anti-TPO antibodies. Treatment is also advised especially for middle-aged patients with cardiovascular risk factors such as hyperlipidemia or hypertension and in pregnant patients. Surgery may occa-sionally be indicated for suspicion of malignancy or for goiters causing compressive symptoms or cosmetic deformity.Riedel’s Thyroiditis Riedel’s thyroiditis is a rare variant of thyroiditis also known as Riedel’s struma or invasive fibrous thyroiditis that is characterized by the replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues. The etiology of this disorder is contro-versial, and it has been reported to occur in |
Surgery_Schwartz_10816 | Surgery_Schwartz | replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues. The etiology of this disorder is contro-versial, and it has been reported to occur in patients with other autoimmune diseases. This association, coupled with the pres-ence of lymphoid infiltration and response to steroid therapy, suggests a primary autoimmune etiology. Riedel’s thyroiditis also is associated with other focal sclerosing syndromes includ-ing mediastinal, retroperitoneal, periorbital, and retro-orbital fibrosis and sclerosing cholangitis, suggesting that it may, in fact, be a primary fibrotic disorder. It is now considered a manifestation of IgG4-related systemic disease characterized by elevated serum IgG4 levels and a lymphoplasmacytic infiltrate with an abundance of IgG4 bearing plasma cells.14 The disease occurs predominantly in women between the ages of 30 and 60 years old. It typically presents as a painless, hard anterior neck mass, which progresses | Surgery_Schwartz. replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues. The etiology of this disorder is contro-versial, and it has been reported to occur in patients with other autoimmune diseases. This association, coupled with the pres-ence of lymphoid infiltration and response to steroid therapy, suggests a primary autoimmune etiology. Riedel’s thyroiditis also is associated with other focal sclerosing syndromes includ-ing mediastinal, retroperitoneal, periorbital, and retro-orbital fibrosis and sclerosing cholangitis, suggesting that it may, in fact, be a primary fibrotic disorder. It is now considered a manifestation of IgG4-related systemic disease characterized by elevated serum IgG4 levels and a lymphoplasmacytic infiltrate with an abundance of IgG4 bearing plasma cells.14 The disease occurs predominantly in women between the ages of 30 and 60 years old. It typically presents as a painless, hard anterior neck mass, which progresses |
Surgery_Schwartz_10817 | Surgery_Schwartz | of IgG4 bearing plasma cells.14 The disease occurs predominantly in women between the ages of 30 and 60 years old. It typically presents as a painless, hard anterior neck mass, which progresses over weeks to years to produce symptoms of compression, including dysphagia, dyspnea, chok-ing, and hoarseness. Patients may present with symptoms of hypothyroidism and hypoparathyroidism as the gland is replaced by fibrous tissue. Physical examination reveals a hard, “woody” thyroid gland with fixation to surrounding tissues. The diagnosis needs to be confirmed by open thyroid biopsy because the firm and fibrous nature of the gland renders FNAB inadequate.Surgery is the mainstay of the treatment. The chief goal of operation is to decompress the trachea by wedge excision of the thyroid isthmus and to make a tissue diagnosis. More extensive resections are not advised due to the infiltrative nature of the fibrotic process that obscures usual landmarks and struc-tures. Hypothyroid patients are | Surgery_Schwartz. of IgG4 bearing plasma cells.14 The disease occurs predominantly in women between the ages of 30 and 60 years old. It typically presents as a painless, hard anterior neck mass, which progresses over weeks to years to produce symptoms of compression, including dysphagia, dyspnea, chok-ing, and hoarseness. Patients may present with symptoms of hypothyroidism and hypoparathyroidism as the gland is replaced by fibrous tissue. Physical examination reveals a hard, “woody” thyroid gland with fixation to surrounding tissues. The diagnosis needs to be confirmed by open thyroid biopsy because the firm and fibrous nature of the gland renders FNAB inadequate.Surgery is the mainstay of the treatment. The chief goal of operation is to decompress the trachea by wedge excision of the thyroid isthmus and to make a tissue diagnosis. More extensive resections are not advised due to the infiltrative nature of the fibrotic process that obscures usual landmarks and struc-tures. Hypothyroid patients are |
Surgery_Schwartz_10818 | Surgery_Schwartz | to make a tissue diagnosis. More extensive resections are not advised due to the infiltrative nature of the fibrotic process that obscures usual landmarks and struc-tures. Hypothyroid patients are treated with thyroid hormone replacement. Some patients who remain symptomatic have been reported to experience dramatic improvement after treatment with corticosteroids and tamoxifen. Mycophenolate mofetil and more recently rituximab has also been used to attenuate the Brunicardi_Ch38_p1625-p1704.indd 164001/03/19 11:20 AM 1641THYROID, PARATHYROID, AND ADRENALCHAPTER 38inflammatory process and led to dramatic symptom improve-ments in some patients.15Goiter. Any enlargement of the thyroid gland is referred to as a goiter. The causes of nontoxic goiters are listed in Table 38-3. Goiters may be diffuse, uninodular, or multinodular. Most non-toxic goiters are thought to result from TSH stimulation second-ary to inadequate thyroid hormone synthesis and other paracrine growth factors.16 | Surgery_Schwartz. to make a tissue diagnosis. More extensive resections are not advised due to the infiltrative nature of the fibrotic process that obscures usual landmarks and struc-tures. Hypothyroid patients are treated with thyroid hormone replacement. Some patients who remain symptomatic have been reported to experience dramatic improvement after treatment with corticosteroids and tamoxifen. Mycophenolate mofetil and more recently rituximab has also been used to attenuate the Brunicardi_Ch38_p1625-p1704.indd 164001/03/19 11:20 AM 1641THYROID, PARATHYROID, AND ADRENALCHAPTER 38inflammatory process and led to dramatic symptom improve-ments in some patients.15Goiter. Any enlargement of the thyroid gland is referred to as a goiter. The causes of nontoxic goiters are listed in Table 38-3. Goiters may be diffuse, uninodular, or multinodular. Most non-toxic goiters are thought to result from TSH stimulation second-ary to inadequate thyroid hormone synthesis and other paracrine growth factors.16 |
Surgery_Schwartz_10819 | Surgery_Schwartz | may be diffuse, uninodular, or multinodular. Most non-toxic goiters are thought to result from TSH stimulation second-ary to inadequate thyroid hormone synthesis and other paracrine growth factors.16 Elevated TSH levels induce diffuse thyroid hyperplasia, followed by focal hyperplasia, resulting in nod-ules that may or may not concentrate iodine, colloid nodules, or microfollicular nodules. The TSH-dependent nodules progress to become autonomous. Familial goiters resulting from inher-ited deficiencies in enzymes necessary for thyroid hormone synthesis may be complete or partial. The term endemic goiter refers to the occurrence of a goiter in a significant proportion of individuals in a particular geographic region. In the past, dietary iodine deficiency was the most common cause of endemic goi-ter. This condition has largely disappeared in North America due to routine use of iodized salt and iodination of fertilizers, animal feeds, and preservatives. However, in areas of iodine | Surgery_Schwartz. may be diffuse, uninodular, or multinodular. Most non-toxic goiters are thought to result from TSH stimulation second-ary to inadequate thyroid hormone synthesis and other paracrine growth factors.16 Elevated TSH levels induce diffuse thyroid hyperplasia, followed by focal hyperplasia, resulting in nod-ules that may or may not concentrate iodine, colloid nodules, or microfollicular nodules. The TSH-dependent nodules progress to become autonomous. Familial goiters resulting from inher-ited deficiencies in enzymes necessary for thyroid hormone synthesis may be complete or partial. The term endemic goiter refers to the occurrence of a goiter in a significant proportion of individuals in a particular geographic region. In the past, dietary iodine deficiency was the most common cause of endemic goi-ter. This condition has largely disappeared in North America due to routine use of iodized salt and iodination of fertilizers, animal feeds, and preservatives. However, in areas of iodine |
Surgery_Schwartz_10820 | Surgery_Schwartz | endemic goi-ter. This condition has largely disappeared in North America due to routine use of iodized salt and iodination of fertilizers, animal feeds, and preservatives. However, in areas of iodine deficiency, such as Central Asia, South America, and Indonesia, up to 90% of the population have goiters. Other dietary goitro-gens that may participate in endemic goiter formation include kelp, cassava, and cabbage. In many sporadic goiters, no obvi-ous cause can be identified.Clinical Features Most patients with nontoxic goiters are asymptomatic, although patients often complain of a pres-sure sensation in the neck. As the goiters become very large, compressive symptoms such as dyspnea and dysphagia ensue. Patients also describe having to clear their throats frequently (catarrh). Dysphonia from RLN injury is rare, except when malignancy is present. Obstruction of venous return at the tho-racic inlet from a substernal goiter results in a positive Pember-ton’s sign—facial flushing and | Surgery_Schwartz. endemic goi-ter. This condition has largely disappeared in North America due to routine use of iodized salt and iodination of fertilizers, animal feeds, and preservatives. However, in areas of iodine deficiency, such as Central Asia, South America, and Indonesia, up to 90% of the population have goiters. Other dietary goitro-gens that may participate in endemic goiter formation include kelp, cassava, and cabbage. In many sporadic goiters, no obvi-ous cause can be identified.Clinical Features Most patients with nontoxic goiters are asymptomatic, although patients often complain of a pres-sure sensation in the neck. As the goiters become very large, compressive symptoms such as dyspnea and dysphagia ensue. Patients also describe having to clear their throats frequently (catarrh). Dysphonia from RLN injury is rare, except when malignancy is present. Obstruction of venous return at the tho-racic inlet from a substernal goiter results in a positive Pember-ton’s sign—facial flushing and |
Surgery_Schwartz_10821 | Surgery_Schwartz | from RLN injury is rare, except when malignancy is present. Obstruction of venous return at the tho-racic inlet from a substernal goiter results in a positive Pember-ton’s sign—facial flushing and dilatation of cervical veins upon raising the arms above the head (Fig. 38-13A). Sudden enlarge-ment of nodules or cysts due to hemorrhage may cause acute pain. Physical examination may reveal a soft, diffusely enlarged gland (simple goiter) or nodules of various size and consistency in case of a multinodular goiter. Deviation or compression of the trachea may be apparent.Diagnostic Tests Patients usually are euthyroid with normal TSH and low-normal or normal free T4 levels. If some nod-ules develop autonomy, patients have suppressed TSH levels or become hyperthyroid. RAI uptake often shows patchy uptake with areas of hot and cold nodules. FNAB is recommended in patients who have a dominant nodule or one that is painful or enlarging, as carcinomas have been reported in 5% to 10% of | Surgery_Schwartz. from RLN injury is rare, except when malignancy is present. Obstruction of venous return at the tho-racic inlet from a substernal goiter results in a positive Pember-ton’s sign—facial flushing and dilatation of cervical veins upon raising the arms above the head (Fig. 38-13A). Sudden enlarge-ment of nodules or cysts due to hemorrhage may cause acute pain. Physical examination may reveal a soft, diffusely enlarged gland (simple goiter) or nodules of various size and consistency in case of a multinodular goiter. Deviation or compression of the trachea may be apparent.Diagnostic Tests Patients usually are euthyroid with normal TSH and low-normal or normal free T4 levels. If some nod-ules develop autonomy, patients have suppressed TSH levels or become hyperthyroid. RAI uptake often shows patchy uptake with areas of hot and cold nodules. FNAB is recommended in patients who have a dominant nodule or one that is painful or enlarging, as carcinomas have been reported in 5% to 10% of |
Surgery_Schwartz_10822 | Surgery_Schwartz | patchy uptake with areas of hot and cold nodules. FNAB is recommended in patients who have a dominant nodule or one that is painful or enlarging, as carcinomas have been reported in 5% to 10% of multinodular goiters. CT scans are helpful to evaluate the extent of retrosternal extension and airway compression (Fig. 38-13B).Treatment Most euthyroid patients with small, diffuse goi-ters do not require treatment. Some physicians give patients with large goiters exogenous thyroid hormone to reduce the TSH stimulation of gland growth; this treatment may result in decrease and/or stabilization of goiter size and is most effective for small diffuse goiters. Endemic goiters are treated by iodine administration. Surgical resection is reserved for goiters that (a) continue to increase despite T4 suppression, (b) cause obstruc-tive symptoms, (c) have substernal extension (considered a rela-tive indication by some groups), (d) have malignancy suspected or proven by FNAB, and (e) are cosmetically | Surgery_Schwartz. patchy uptake with areas of hot and cold nodules. FNAB is recommended in patients who have a dominant nodule or one that is painful or enlarging, as carcinomas have been reported in 5% to 10% of multinodular goiters. CT scans are helpful to evaluate the extent of retrosternal extension and airway compression (Fig. 38-13B).Treatment Most euthyroid patients with small, diffuse goi-ters do not require treatment. Some physicians give patients with large goiters exogenous thyroid hormone to reduce the TSH stimulation of gland growth; this treatment may result in decrease and/or stabilization of goiter size and is most effective for small diffuse goiters. Endemic goiters are treated by iodine administration. Surgical resection is reserved for goiters that (a) continue to increase despite T4 suppression, (b) cause obstruc-tive symptoms, (c) have substernal extension (considered a rela-tive indication by some groups), (d) have malignancy suspected or proven by FNAB, and (e) are cosmetically |
Surgery_Schwartz_10823 | Surgery_Schwartz | (b) cause obstruc-tive symptoms, (c) have substernal extension (considered a rela-tive indication by some groups), (d) have malignancy suspected or proven by FNAB, and (e) are cosmetically unacceptable. Near-total or total thyroidectomy is the treatment of choice, and patients require lifelong T4 therapy.Solitary Thyroid NoduleSolitary thyroid nodules are present in approximately 4% of individuals in the United States, whereas thyroid cancer has a much lower incidence of 40 new cases per 1 million. Therefore, it is of utmost importance to determine which patients with soli-tary thyroid nodule would benefit from surgery.History. Details regarding the nodule, such as time of onset, change in size, and associated symptoms such as pain, dyspha-gia, dyspnea, or choking, should be elicited. Pain is an unusual symptom and, when present, should raise suspicion for intra-thyroidal hemorrhage in a benign nodule, thyroiditis, or malig-nancy. Patients with MTC may complain of a dull, aching | Surgery_Schwartz. (b) cause obstruc-tive symptoms, (c) have substernal extension (considered a rela-tive indication by some groups), (d) have malignancy suspected or proven by FNAB, and (e) are cosmetically unacceptable. Near-total or total thyroidectomy is the treatment of choice, and patients require lifelong T4 therapy.Solitary Thyroid NoduleSolitary thyroid nodules are present in approximately 4% of individuals in the United States, whereas thyroid cancer has a much lower incidence of 40 new cases per 1 million. Therefore, it is of utmost importance to determine which patients with soli-tary thyroid nodule would benefit from surgery.History. Details regarding the nodule, such as time of onset, change in size, and associated symptoms such as pain, dyspha-gia, dyspnea, or choking, should be elicited. Pain is an unusual symptom and, when present, should raise suspicion for intra-thyroidal hemorrhage in a benign nodule, thyroiditis, or malig-nancy. Patients with MTC may complain of a dull, aching |
Surgery_Schwartz_10824 | Surgery_Schwartz | Pain is an unusual symptom and, when present, should raise suspicion for intra-thyroidal hemorrhage in a benign nodule, thyroiditis, or malig-nancy. Patients with MTC may complain of a dull, aching sensation. A history of hoarseness is worrisome, as it may be secondary to malignant involvement of the RLNs. Most impor-tantly, patients should be questioned regarding risk factors for malignancy, such as exposure to ionizing radiation and family history of thyroid and other malignancies associated with thy-roid cancer.External-Beam Radiation Low-dose therapeutic radiation has been used to treat conditions such as tinea capitis (6.5 cGy), thymic enlargement (100 to 400 cGy), enlarged tonsils and adenoids (750 cGy), acne vulgaris (200 to 1500 cGy), and other conditions such as hemangioma and scrofula. Radiation (approximately 4000 cGy) is also an integral part of the manage-ment of patients with Hodgkin’s disease. It is now known that a history of exposure to low-dose ionizing radiation to | Surgery_Schwartz. Pain is an unusual symptom and, when present, should raise suspicion for intra-thyroidal hemorrhage in a benign nodule, thyroiditis, or malig-nancy. Patients with MTC may complain of a dull, aching sensation. A history of hoarseness is worrisome, as it may be secondary to malignant involvement of the RLNs. Most impor-tantly, patients should be questioned regarding risk factors for malignancy, such as exposure to ionizing radiation and family history of thyroid and other malignancies associated with thy-roid cancer.External-Beam Radiation Low-dose therapeutic radiation has been used to treat conditions such as tinea capitis (6.5 cGy), thymic enlargement (100 to 400 cGy), enlarged tonsils and adenoids (750 cGy), acne vulgaris (200 to 1500 cGy), and other conditions such as hemangioma and scrofula. Radiation (approximately 4000 cGy) is also an integral part of the manage-ment of patients with Hodgkin’s disease. It is now known that a history of exposure to low-dose ionizing radiation to |
Surgery_Schwartz_10825 | Surgery_Schwartz | Radiation (approximately 4000 cGy) is also an integral part of the manage-ment of patients with Hodgkin’s disease. It is now known that a history of exposure to low-dose ionizing radiation to the thyroid gland places the patient at increased risk for developing thyroid cancer. The risk increases linearly from 6.5 to 2000 cGy, beyond which the incidence declines as the radiation causes destruc-tion of the thyroid tissue. The risk is maximum 20 to 30 years after exposure, but these patients require lifelong monitoring. During the nuclear fallout from Chernobyl in 1986, 131I release was accompanied by a marked increase in the incidence of both benign and malignant thyroid lesions noted within 4 years of exposure, particularly in children.17 Most thyroid carcinomas following radiation exposure are papillary, and some of these cancers with a solid type of histology and presence of RET/PTC translocations appear to be more aggressive. In general, there is a 40% chance that patients | Surgery_Schwartz. Radiation (approximately 4000 cGy) is also an integral part of the manage-ment of patients with Hodgkin’s disease. It is now known that a history of exposure to low-dose ionizing radiation to the thyroid gland places the patient at increased risk for developing thyroid cancer. The risk increases linearly from 6.5 to 2000 cGy, beyond which the incidence declines as the radiation causes destruc-tion of the thyroid tissue. The risk is maximum 20 to 30 years after exposure, but these patients require lifelong monitoring. During the nuclear fallout from Chernobyl in 1986, 131I release was accompanied by a marked increase in the incidence of both benign and malignant thyroid lesions noted within 4 years of exposure, particularly in children.17 Most thyroid carcinomas following radiation exposure are papillary, and some of these cancers with a solid type of histology and presence of RET/PTC translocations appear to be more aggressive. In general, there is a 40% chance that patients |
Surgery_Schwartz_10826 | Surgery_Schwartz | exposure are papillary, and some of these cancers with a solid type of histology and presence of RET/PTC translocations appear to be more aggressive. In general, there is a 40% chance that patients presenting with a thyroid nodule and a history of radiation have thyroid cancer. Of those patients who have thyroid cancer, the cancer is located in the dominant nodule in 60% of patients, but in the remaining 40% of patients, the cancer is in another nodule in the thyroid gland.Table 38-3Etiology of nontoxic goiterCLASSIFICATIONSPECIFIC ETIOLOGYEndemicIodine deficiency, dietary goitrogens (cassava, cabbage)MedicationsIodide, amiodarone, lithiumThyroiditisSubacute, chronic (Hashimoto’s)FamilialImpaired hormone synthesis from enzyme defectsNeoplasmAdenoma, carcinomaResistance to thyroid hormone—Brunicardi_Ch38_p1625-p1704.indd 164101/03/19 11:20 AM 1642SPECIFIC CONSIDERATIONSPART IIABFigure 38-13. A. Retrosternal extension of a large goiter may result in impeded flow in the superior vena | Surgery_Schwartz. exposure are papillary, and some of these cancers with a solid type of histology and presence of RET/PTC translocations appear to be more aggressive. In general, there is a 40% chance that patients presenting with a thyroid nodule and a history of radiation have thyroid cancer. Of those patients who have thyroid cancer, the cancer is located in the dominant nodule in 60% of patients, but in the remaining 40% of patients, the cancer is in another nodule in the thyroid gland.Table 38-3Etiology of nontoxic goiterCLASSIFICATIONSPECIFIC ETIOLOGYEndemicIodine deficiency, dietary goitrogens (cassava, cabbage)MedicationsIodide, amiodarone, lithiumThyroiditisSubacute, chronic (Hashimoto’s)FamilialImpaired hormone synthesis from enzyme defectsNeoplasmAdenoma, carcinomaResistance to thyroid hormone—Brunicardi_Ch38_p1625-p1704.indd 164101/03/19 11:20 AM 1642SPECIFIC CONSIDERATIONSPART IIABFigure 38-13. A. Retrosternal extension of a large goiter may result in impeded flow in the superior vena |
Surgery_Schwartz_10827 | Surgery_Schwartz | 164101/03/19 11:20 AM 1642SPECIFIC CONSIDERATIONSPART IIABFigure 38-13. A. Retrosternal extension of a large goiter may result in impeded flow in the superior vena cava, leading to dilated veins over the chest wall. This may become more prominent when patients raise their arms above the head—Pemberton’s sign. B. Computed tomography scan demonstrating retrosternal extension and consequent tracheal deviation and compression from a large goiter.Brunicardi_Ch38_p1625-p1704.indd 164201/03/19 11:20 AM 1643THYROID, PARATHYROID, AND ADRENALCHAPTER 38Family History A family history of thyroid cancer is a risk factor for the development of both medullary and nonmedullary thyroid cancer. Familial MTCs occur in isolation or in associa-tion with other tumors as part of multiple endocrine neoplasia type 2 (MEN2) syndromes. Nonmedullary thyroid cancers can occur in association with other known familial cancer syn-dromes such as Cowden’s syndrome, Werner’s syndrome (adult progeroid syndrome), | Surgery_Schwartz. 164101/03/19 11:20 AM 1642SPECIFIC CONSIDERATIONSPART IIABFigure 38-13. A. Retrosternal extension of a large goiter may result in impeded flow in the superior vena cava, leading to dilated veins over the chest wall. This may become more prominent when patients raise their arms above the head—Pemberton’s sign. B. Computed tomography scan demonstrating retrosternal extension and consequent tracheal deviation and compression from a large goiter.Brunicardi_Ch38_p1625-p1704.indd 164201/03/19 11:20 AM 1643THYROID, PARATHYROID, AND ADRENALCHAPTER 38Family History A family history of thyroid cancer is a risk factor for the development of both medullary and nonmedullary thyroid cancer. Familial MTCs occur in isolation or in associa-tion with other tumors as part of multiple endocrine neoplasia type 2 (MEN2) syndromes. Nonmedullary thyroid cancers can occur in association with other known familial cancer syn-dromes such as Cowden’s syndrome, Werner’s syndrome (adult progeroid syndrome), |
Surgery_Schwartz_10828 | Surgery_Schwartz | type 2 (MEN2) syndromes. Nonmedullary thyroid cancers can occur in association with other known familial cancer syn-dromes such as Cowden’s syndrome, Werner’s syndrome (adult progeroid syndrome), familial adenomatous polyposis, and DICER 1 (Table 38-4). Nonmedullary thyroid cancers can also occur independently of these syndromes as the predominant tumors in the families, and in fact nonsyndromic FNMTC accounts for 95% of cases. The definition of familial nonmedul-lary thyroid cancer (FNMTC) is variable across the literature; however, in most studies, it is defined by the presence of two or more first-degree relatives with follicular cell–derived cancers. FNMTC is now recognized as a distinct clinical entity associated with a high incidence of multifocal tumors and benign thyroid nodules. Some studies report that these patients have higher locoregional recurrence rates and consequently shorter disease-free survival. Several candidate chromosomal loci that predispose to these tumors | Surgery_Schwartz. type 2 (MEN2) syndromes. Nonmedullary thyroid cancers can occur in association with other known familial cancer syn-dromes such as Cowden’s syndrome, Werner’s syndrome (adult progeroid syndrome), familial adenomatous polyposis, and DICER 1 (Table 38-4). Nonmedullary thyroid cancers can also occur independently of these syndromes as the predominant tumors in the families, and in fact nonsyndromic FNMTC accounts for 95% of cases. The definition of familial nonmedul-lary thyroid cancer (FNMTC) is variable across the literature; however, in most studies, it is defined by the presence of two or more first-degree relatives with follicular cell–derived cancers. FNMTC is now recognized as a distinct clinical entity associated with a high incidence of multifocal tumors and benign thyroid nodules. Some studies report that these patients have higher locoregional recurrence rates and consequently shorter disease-free survival. Several candidate chromosomal loci that predispose to these tumors |
Surgery_Schwartz_10829 | Surgery_Schwartz | Some studies report that these patients have higher locoregional recurrence rates and consequently shorter disease-free survival. Several candidate chromosomal loci that predispose to these tumors have been identified, includ-ing MNG1 (14q32), thyroid carcinoma with oxphilia (TCO, on 19p13.2), fPTC/papillary renal neoplasia (PRN, on 1q21), NMTC1 (2q21), and FTEN (8p23.1-p22). Susceptibility genes include SRGAP1 (12q14), TITF-1/NKX2.1 (14q13), FOXE1 (9q22), and the telomere-telomerase complex.18Physical Examination. The thyroid gland is best palpated from behind the patient and with the neck in mild extension. The cricoid cartilage is an important landmark, as the isthmus is situated just below it. Nodules that are hard, gritty, or fixed to surrounding structures such as the trachea or strap muscles are more likely to be malignant. The cervical chain of lymph nodes should be assessed as well as the nodes in the posterior triangle.Diagnostic Investigations. An algorithm for the workup | Surgery_Schwartz. Some studies report that these patients have higher locoregional recurrence rates and consequently shorter disease-free survival. Several candidate chromosomal loci that predispose to these tumors have been identified, includ-ing MNG1 (14q32), thyroid carcinoma with oxphilia (TCO, on 19p13.2), fPTC/papillary renal neoplasia (PRN, on 1q21), NMTC1 (2q21), and FTEN (8p23.1-p22). Susceptibility genes include SRGAP1 (12q14), TITF-1/NKX2.1 (14q13), FOXE1 (9q22), and the telomere-telomerase complex.18Physical Examination. The thyroid gland is best palpated from behind the patient and with the neck in mild extension. The cricoid cartilage is an important landmark, as the isthmus is situated just below it. Nodules that are hard, gritty, or fixed to surrounding structures such as the trachea or strap muscles are more likely to be malignant. The cervical chain of lymph nodes should be assessed as well as the nodes in the posterior triangle.Diagnostic Investigations. An algorithm for the workup |
Surgery_Schwartz_10830 | Surgery_Schwartz | muscles are more likely to be malignant. The cervical chain of lymph nodes should be assessed as well as the nodes in the posterior triangle.Diagnostic Investigations. An algorithm for the workup of a solitary thyroid nodule is shown in Fig. 38-14.Fine-Needle Aspiration Biopsy FNAB has become the single most important test in the evaluation of thyroid masses and can be performed with or without ultrasound guidance. Ultrasound guidance is recommended for nodules that are difficult to pal-pate, for cystic or solid-cystic nodules that recur after the initial aspiration, and for multinodular goiters. A 23-gauge needle is inserted into the thyroid mass, and several passes are made while aspirating the syringe. After releasing the suction on the syringe, the needle is withdrawn and the cells are immediately placed on prelabeled dry glass slides; some are immersed in a 70% alcohol solution while others are air dried. A sample of the aspirate is also placed in a 90% alcohol solution for | Surgery_Schwartz. muscles are more likely to be malignant. The cervical chain of lymph nodes should be assessed as well as the nodes in the posterior triangle.Diagnostic Investigations. An algorithm for the workup of a solitary thyroid nodule is shown in Fig. 38-14.Fine-Needle Aspiration Biopsy FNAB has become the single most important test in the evaluation of thyroid masses and can be performed with or without ultrasound guidance. Ultrasound guidance is recommended for nodules that are difficult to pal-pate, for cystic or solid-cystic nodules that recur after the initial aspiration, and for multinodular goiters. A 23-gauge needle is inserted into the thyroid mass, and several passes are made while aspirating the syringe. After releasing the suction on the syringe, the needle is withdrawn and the cells are immediately placed on prelabeled dry glass slides; some are immersed in a 70% alcohol solution while others are air dried. A sample of the aspirate is also placed in a 90% alcohol solution for |
Surgery_Schwartz_10831 | Surgery_Schwartz | are immediately placed on prelabeled dry glass slides; some are immersed in a 70% alcohol solution while others are air dried. A sample of the aspirate is also placed in a 90% alcohol solution for cytospin or cell pellet. The slides are stained by Papanicolaou’s or Wright’s stains and examined under the microscope. If a bloody aspirate is obtained, the patient should be repositioned in a more upright position and the biopsy repeated with a finer (25to 30-gauge) needle.After FNAB, the majority of nodules can be classified into several categories that determine further management. To address the issue of variability in the terminology of fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the “NCI Thyroid Fine Needle Aspiration State of the Science Conference,” which then defined the Bethesda criteria for thyroid FNA.19 Accordingly, optimum cytology specimens should have at least six follicles each containing at least 10 to 15 cells from at least two aspirates.The | Surgery_Schwartz. are immediately placed on prelabeled dry glass slides; some are immersed in a 70% alcohol solution while others are air dried. A sample of the aspirate is also placed in a 90% alcohol solution for cytospin or cell pellet. The slides are stained by Papanicolaou’s or Wright’s stains and examined under the microscope. If a bloody aspirate is obtained, the patient should be repositioned in a more upright position and the biopsy repeated with a finer (25to 30-gauge) needle.After FNAB, the majority of nodules can be classified into several categories that determine further management. To address the issue of variability in the terminology of fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the “NCI Thyroid Fine Needle Aspiration State of the Science Conference,” which then defined the Bethesda criteria for thyroid FNA.19 Accordingly, optimum cytology specimens should have at least six follicles each containing at least 10 to 15 cells from at least two aspirates.The |
Surgery_Schwartz_10832 | Surgery_Schwartz | defined the Bethesda criteria for thyroid FNA.19 Accordingly, optimum cytology specimens should have at least six follicles each containing at least 10 to 15 cells from at least two aspirates.The FNA is classified as “nondiagnostic or unsatisfac-tory” in 2% to 20% of cases and typically results from a virtu-ally acellular specimen, cyst fluid, or the presence of blood or clotting artifact. The risk of malignancy in this setting ranges from 1% to 4%, and reaspiration under ultrasound guidance is recommended. A “benign” result is obtained in 60% to 70% of thyroid FNAs. The most common lesion in this setting is a follicular nodule (includes adenomatoid nodule, colloid nodule, and follicular adenoma). Other diagnoses include lymphocytic (Hashimoto’s) thyroiditis and granulomatous thyroiditis. False-negative results are reported in up to 3% of cases, and follow-up is recommended. A result of “atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)” is | Surgery_Schwartz. defined the Bethesda criteria for thyroid FNA.19 Accordingly, optimum cytology specimens should have at least six follicles each containing at least 10 to 15 cells from at least two aspirates.The FNA is classified as “nondiagnostic or unsatisfac-tory” in 2% to 20% of cases and typically results from a virtu-ally acellular specimen, cyst fluid, or the presence of blood or clotting artifact. The risk of malignancy in this setting ranges from 1% to 4%, and reaspiration under ultrasound guidance is recommended. A “benign” result is obtained in 60% to 70% of thyroid FNAs. The most common lesion in this setting is a follicular nodule (includes adenomatoid nodule, colloid nodule, and follicular adenoma). Other diagnoses include lymphocytic (Hashimoto’s) thyroiditis and granulomatous thyroiditis. False-negative results are reported in up to 3% of cases, and follow-up is recommended. A result of “atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)” is |
Surgery_Schwartz_10833 | Surgery_Schwartz | False-negative results are reported in up to 3% of cases, and follow-up is recommended. A result of “atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)” is obtained in 3% to 6% of biopsies. The risk of malignancy in this scenario is difficult to determine; however, it is thought to be in the range of 5% to 15%. Clinical correlation and a repeat FNA are recommended for AUS lesions (which often results in 23Table 38-4Familial cancer syndromes involving nonmedullary thyroid cancerSYNDROMEGENEMANIFESTATIONTHYROID TUMORCowden’s syndromePTENIntestinal hamartomas, benign and malignant breast tumorsFTC, rarely PTC and Hürthle cell tumorsFAPAPCColon polyps and cancer, duodenal neoplasms, desmoidsPTC cribriform growth patternWerner’s syndromeWRNAdult progeroid syndromePTC, FTC, anaplastic cancerCarney complex type 1PRKAR1αCutaneous and cardiac myxomas, breast and adrenal tumorsPTC, FTCMcCune-Albright syndromeGNAS1Polyostotic fibrous dysplasia, endocrine | Surgery_Schwartz. False-negative results are reported in up to 3% of cases, and follow-up is recommended. A result of “atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)” is obtained in 3% to 6% of biopsies. The risk of malignancy in this scenario is difficult to determine; however, it is thought to be in the range of 5% to 15%. Clinical correlation and a repeat FNA are recommended for AUS lesions (which often results in 23Table 38-4Familial cancer syndromes involving nonmedullary thyroid cancerSYNDROMEGENEMANIFESTATIONTHYROID TUMORCowden’s syndromePTENIntestinal hamartomas, benign and malignant breast tumorsFTC, rarely PTC and Hürthle cell tumorsFAPAPCColon polyps and cancer, duodenal neoplasms, desmoidsPTC cribriform growth patternWerner’s syndromeWRNAdult progeroid syndromePTC, FTC, anaplastic cancerCarney complex type 1PRKAR1αCutaneous and cardiac myxomas, breast and adrenal tumorsPTC, FTCMcCune-Albright syndromeGNAS1Polyostotic fibrous dysplasia, endocrine |
Surgery_Schwartz_10834 | Surgery_Schwartz | syndromePTC, FTC, anaplastic cancerCarney complex type 1PRKAR1αCutaneous and cardiac myxomas, breast and adrenal tumorsPTC, FTCMcCune-Albright syndromeGNAS1Polyostotic fibrous dysplasia, endocrine abnormalities, café-au-lait spotsPTC clear cellDICER 1 syndrome Pleuropulmonary blastoma, cystic nephroma, ovarian sex cord-stromal tumorsMultinodular goiter, thyroid cancerFAP = familial adenomatous polyposis; FTC = follicular thyroid cancer; PTC = papillary thyroid cancer.Brunicardi_Ch38_p1625-p1704.indd 164301/03/19 11:20 AM 1644SPECIFIC CONSIDERATIONSPART IIa more definitive interpretation), although clinical observation or surgery may be appropriate because of worrisome clinical or ultrasound findings. The category of “follicular neoplasm” is intended to identify nodules that might be follicular carcinomas. The term suspicious for a follicular neoplasm is preferred by some laboratories for this category because up to 35% of cases turn out not to be neoplasms but hyperplastic | Surgery_Schwartz. syndromePTC, FTC, anaplastic cancerCarney complex type 1PRKAR1αCutaneous and cardiac myxomas, breast and adrenal tumorsPTC, FTCMcCune-Albright syndromeGNAS1Polyostotic fibrous dysplasia, endocrine abnormalities, café-au-lait spotsPTC clear cellDICER 1 syndrome Pleuropulmonary blastoma, cystic nephroma, ovarian sex cord-stromal tumorsMultinodular goiter, thyroid cancerFAP = familial adenomatous polyposis; FTC = follicular thyroid cancer; PTC = papillary thyroid cancer.Brunicardi_Ch38_p1625-p1704.indd 164301/03/19 11:20 AM 1644SPECIFIC CONSIDERATIONSPART IIa more definitive interpretation), although clinical observation or surgery may be appropriate because of worrisome clinical or ultrasound findings. The category of “follicular neoplasm” is intended to identify nodules that might be follicular carcinomas. The term suspicious for a follicular neoplasm is preferred by some laboratories for this category because up to 35% of cases turn out not to be neoplasms but hyperplastic |
Surgery_Schwartz_10835 | Surgery_Schwartz | be follicular carcinomas. The term suspicious for a follicular neoplasm is preferred by some laboratories for this category because up to 35% of cases turn out not to be neoplasms but hyperplastic proliferations of follicular cells, most commonly those of multinodular goiter. Lobectomy is the preferred treatment for this result, and approx-imately 15% to 35% of lesions placed in this category prove to be malignant. Hürthle cell neoplasms are also included in this category. Most papillary and other carcinomas can be diagnosed by FNA, but the features are subtle at times, such as in follicular variant of papillary carcinomas. If the diagnosis is uncertain, the lesions are classified as “suspicious for malignancy.” Lobec-tomy or near-total thyroidectomy is recommended because 60% to 75% turn out to be malignant. This category also includes lesions suspicious for medullary carcinoma and lymphoma, and ancillary testing such as immunohistochemical analysis and flow cytometry may be helpful. | Surgery_Schwartz. be follicular carcinomas. The term suspicious for a follicular neoplasm is preferred by some laboratories for this category because up to 35% of cases turn out not to be neoplasms but hyperplastic proliferations of follicular cells, most commonly those of multinodular goiter. Lobectomy is the preferred treatment for this result, and approx-imately 15% to 35% of lesions placed in this category prove to be malignant. Hürthle cell neoplasms are also included in this category. Most papillary and other carcinomas can be diagnosed by FNA, but the features are subtle at times, such as in follicular variant of papillary carcinomas. If the diagnosis is uncertain, the lesions are classified as “suspicious for malignancy.” Lobec-tomy or near-total thyroidectomy is recommended because 60% to 75% turn out to be malignant. This category also includes lesions suspicious for medullary carcinoma and lymphoma, and ancillary testing such as immunohistochemical analysis and flow cytometry may be helpful. |
Surgery_Schwartz_10836 | Surgery_Schwartz | out to be malignant. This category also includes lesions suspicious for medullary carcinoma and lymphoma, and ancillary testing such as immunohistochemical analysis and flow cytometry may be helpful. The risk of malignancy in lesions classified as “malignant” by FNA is 97% to 99%, and near-total/total thyroidectomy is recommended.Laboratory Studies Most patients with thyroid nodules are euthyroid. Determining the blood TSH level is helpful. If a patient with a nodule is found to be hyperthyroid, the risk of malignancy is approximately 1%. Serum Tg levels cannot dif-ferentiate benign from malignant thyroid nodules unless the lev-els are extremely high, in which case metastatic thyroid cancer should be suspected. Tg levels are, however, useful in following patients who have undergone total thyroidectomy for thyroid cancer and also for serial evaluation of patients undergoing nonoperative management of thyroid nodules. Serum calcitonin levels should be obtained in patients with MTC or a | Surgery_Schwartz. out to be malignant. This category also includes lesions suspicious for medullary carcinoma and lymphoma, and ancillary testing such as immunohistochemical analysis and flow cytometry may be helpful. The risk of malignancy in lesions classified as “malignant” by FNA is 97% to 99%, and near-total/total thyroidectomy is recommended.Laboratory Studies Most patients with thyroid nodules are euthyroid. Determining the blood TSH level is helpful. If a patient with a nodule is found to be hyperthyroid, the risk of malignancy is approximately 1%. Serum Tg levels cannot dif-ferentiate benign from malignant thyroid nodules unless the lev-els are extremely high, in which case metastatic thyroid cancer should be suspected. Tg levels are, however, useful in following patients who have undergone total thyroidectomy for thyroid cancer and also for serial evaluation of patients undergoing nonoperative management of thyroid nodules. Serum calcitonin levels should be obtained in patients with MTC or a |
Surgery_Schwartz_10837 | Surgery_Schwartz | thyroidectomy for thyroid cancer and also for serial evaluation of patients undergoing nonoperative management of thyroid nodules. Serum calcitonin levels should be obtained in patients with MTC or a family his-tory of MTC or MEN2. There is insufficient evidence to recom-mend routine calcitonin testing for all nodules. All patients with MTC should be tested for RET oncogene mutations and have a 24-hour urine collection with measurement of levels of vanil-lylmandelic acid (VMA), metanephrine, and catecholamine levels to rule out a coexisting pheochromocytoma. About 10% of patients with familial MTC and MEN2A have de novo RET mutations, so that their children are at risk for thyroid cancer.Imaging Ultrasound is helpful for detecting nonpalpable thy-roid nodules, differentiating solid from cystic nodules, and identifying adjacent lymphadenopathy. Ultrasound evaluation can identify features of a nodule that increase the a priori risk of malignancy, such as fine stippled calcification and | Surgery_Schwartz. thyroidectomy for thyroid cancer and also for serial evaluation of patients undergoing nonoperative management of thyroid nodules. Serum calcitonin levels should be obtained in patients with MTC or a family his-tory of MTC or MEN2. There is insufficient evidence to recom-mend routine calcitonin testing for all nodules. All patients with MTC should be tested for RET oncogene mutations and have a 24-hour urine collection with measurement of levels of vanil-lylmandelic acid (VMA), metanephrine, and catecholamine levels to rule out a coexisting pheochromocytoma. About 10% of patients with familial MTC and MEN2A have de novo RET mutations, so that their children are at risk for thyroid cancer.Imaging Ultrasound is helpful for detecting nonpalpable thy-roid nodules, differentiating solid from cystic nodules, and identifying adjacent lymphadenopathy. Ultrasound evaluation can identify features of a nodule that increase the a priori risk of malignancy, such as fine stippled calcification and |
Surgery_Schwartz_10838 | Surgery_Schwartz | nodules, and identifying adjacent lymphadenopathy. Ultrasound evaluation can identify features of a nodule that increase the a priori risk of malignancy, such as fine stippled calcification and enlarged regional nodes; however, a tissue diagnosis is strongly recom-mended before thyroidectomy.20 Ultrasound also provides a noninvasive and inexpensive method of following the size of suspected benign nodules diagnosed by FNAB and for identi-fying enlarged lymph nodes. Ultrasound elastography is used to evaluate tissue stiffness noninvasively. This technique takes advantage of the fact that malignant nodules tend to be harder than benign nodules and thus deform less compared with the surrounding normal thyroid parenchyma. Larger studies are warranted before elastography and newer techniques such as contrast-enhanced ultrasound can be routinely included in the evaluation of thyroid nodules.21 CT and MRI are unnecessary in the routine evaluation of thyroid tumors except for large, fixed, or | Surgery_Schwartz. nodules, and identifying adjacent lymphadenopathy. Ultrasound evaluation can identify features of a nodule that increase the a priori risk of malignancy, such as fine stippled calcification and enlarged regional nodes; however, a tissue diagnosis is strongly recom-mended before thyroidectomy.20 Ultrasound also provides a noninvasive and inexpensive method of following the size of suspected benign nodules diagnosed by FNAB and for identi-fying enlarged lymph nodes. Ultrasound elastography is used to evaluate tissue stiffness noninvasively. This technique takes advantage of the fact that malignant nodules tend to be harder than benign nodules and thus deform less compared with the surrounding normal thyroid parenchyma. Larger studies are warranted before elastography and newer techniques such as contrast-enhanced ultrasound can be routinely included in the evaluation of thyroid nodules.21 CT and MRI are unnecessary in the routine evaluation of thyroid tumors except for large, fixed, or |
Surgery_Schwartz_10839 | Surgery_Schwartz | as contrast-enhanced ultrasound can be routinely included in the evaluation of thyroid nodules.21 CT and MRI are unnecessary in the routine evaluation of thyroid tumors except for large, fixed, or substernal lesions. Scanning the thyroid with 123I or 99mTc is rarely necessary, and thyroid scanning currently is recom-mended in the assessment of thyroid nodules only in patients Solitary thyroid noduleFNABBenignMalignantNondiagnosticRepeatFNAB withu/sguidanceCystColloidnoduleAspirateReaccumulates x 3ThyroidectomyObserveContinuedgrowth,compressivesymptoms+/–FNABAUS/FLUSFN orSuspiciousfor FNSuspiciousformalignancyNear-total/ totalThyroidectomyRepeatFNABLobectomyLobectomy ornear-total/totalthyroidectomyFigure 38-14. Management of a solitary thyroid nodule based on Bethesda criteria. a = except in patients with a history of external radia-tion exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; AUS = atypia of unknown significance; FLUS = follicular lesion | Surgery_Schwartz. as contrast-enhanced ultrasound can be routinely included in the evaluation of thyroid nodules.21 CT and MRI are unnecessary in the routine evaluation of thyroid tumors except for large, fixed, or substernal lesions. Scanning the thyroid with 123I or 99mTc is rarely necessary, and thyroid scanning currently is recom-mended in the assessment of thyroid nodules only in patients Solitary thyroid noduleFNABBenignMalignantNondiagnosticRepeatFNAB withu/sguidanceCystColloidnoduleAspirateReaccumulates x 3ThyroidectomyObserveContinuedgrowth,compressivesymptoms+/–FNABAUS/FLUSFN orSuspiciousfor FNSuspiciousformalignancyNear-total/ totalThyroidectomyRepeatFNABLobectomyLobectomy ornear-total/totalthyroidectomyFigure 38-14. Management of a solitary thyroid nodule based on Bethesda criteria. a = except in patients with a history of external radia-tion exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; AUS = atypia of unknown significance; FLUS = follicular lesion |
Surgery_Schwartz_10840 | Surgery_Schwartz | in patients with a history of external radia-tion exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; AUS = atypia of unknown significance; FLUS = follicular lesion of unknown significance; FN = follicular neoplasm.Brunicardi_Ch38_p1625-p1704.indd 164401/03/19 11:20 AM 1645THYROID, PARATHYROID, AND ADRENALCHAPTER 38who have follicular thyroid nodules on FNAB and a suppressed TSH. PET scanning does not play a major role in the primary evaluation of thyroid nodules.Management. Malignant tumors are treated by thyroidectomy, as discussed earlier and later in this chapter in “Surgical Treat-ment under Malignant Thyroid Disease.” Simple thyroid cysts resolve with aspiration in about 75% of cases, although some require a second or third aspiration. If the cyst persists after three attempts at aspiration, unilateral thyroid lobectomy is rec-ommended. Lobectomy also is recommended for cysts >4 cm in diameter or complex cysts with solid and cystic | Surgery_Schwartz. in patients with a history of external radia-tion exposure or a family history of thyroid cancer; FNAB = fine-needle aspiration biopsy; AUS = atypia of unknown significance; FLUS = follicular lesion of unknown significance; FN = follicular neoplasm.Brunicardi_Ch38_p1625-p1704.indd 164401/03/19 11:20 AM 1645THYROID, PARATHYROID, AND ADRENALCHAPTER 38who have follicular thyroid nodules on FNAB and a suppressed TSH. PET scanning does not play a major role in the primary evaluation of thyroid nodules.Management. Malignant tumors are treated by thyroidectomy, as discussed earlier and later in this chapter in “Surgical Treat-ment under Malignant Thyroid Disease.” Simple thyroid cysts resolve with aspiration in about 75% of cases, although some require a second or third aspiration. If the cyst persists after three attempts at aspiration, unilateral thyroid lobectomy is rec-ommended. Lobectomy also is recommended for cysts >4 cm in diameter or complex cysts with solid and cystic |
Surgery_Schwartz_10841 | Surgery_Schwartz | If the cyst persists after three attempts at aspiration, unilateral thyroid lobectomy is rec-ommended. Lobectomy also is recommended for cysts >4 cm in diameter or complex cysts with solid and cystic components, as the latter have a higher incidence of malignancy (15%). When FNAB is used in complex nodules, the solid portion should be sampled. If a colloid nodule is diagnosed by FNAB, patients should still be observed with serial ultrasound and Tg measure-ments. If the nodule enlarges, repeat FNAB often is indicated. Although controversial, levothyroxine in doses sufficient to maintain a serum TSH level between 0.1 and 1.0 μU/mL may also be administered. In areas with a high prevalence of iodine deficiency, this can decrease nodule size and potentially prevent the growth of new nodules. In iodine-sufficient populations, the data are less impressive. Randomized controlled trial analyses have shown that less than 25% of benign nodules shrink more than 50% with TSH suppression in | Surgery_Schwartz. If the cyst persists after three attempts at aspiration, unilateral thyroid lobectomy is rec-ommended. Lobectomy also is recommended for cysts >4 cm in diameter or complex cysts with solid and cystic components, as the latter have a higher incidence of malignancy (15%). When FNAB is used in complex nodules, the solid portion should be sampled. If a colloid nodule is diagnosed by FNAB, patients should still be observed with serial ultrasound and Tg measure-ments. If the nodule enlarges, repeat FNAB often is indicated. Although controversial, levothyroxine in doses sufficient to maintain a serum TSH level between 0.1 and 1.0 μU/mL may also be administered. In areas with a high prevalence of iodine deficiency, this can decrease nodule size and potentially prevent the growth of new nodules. In iodine-sufficient populations, the data are less impressive. Randomized controlled trial analyses have shown that less than 25% of benign nodules shrink more than 50% with TSH suppression in |
Surgery_Schwartz_10842 | Surgery_Schwartz | In iodine-sufficient populations, the data are less impressive. Randomized controlled trial analyses have shown that less than 25% of benign nodules shrink more than 50% with TSH suppression in iodine-replete populations. Thyroidectomy should be performed if a nodule enlarges on TSH suppression, causes compressive symptoms, or for cos-metic reasons. An exception to this general rule is the patient who has had previous irradiation of the thyroid gland or has a family history of thyroid cancer. In these patients, total or near-total thyroidectomy is recommended because of the high incidence of thyroid cancer and decreased reliability of FNAB in this setting.Malignant Thyroid DiseaseIn the United States, thyroid cancer accounts for <1% of all malignancies (2% of women and 0.5% of men) and is the most rapidly increasing cancer in women. Thyroid cancer is respon-sible for six deaths per million persons annually. Most patients present with a palpable swelling in the neck, which initiates | Surgery_Schwartz. In iodine-sufficient populations, the data are less impressive. Randomized controlled trial analyses have shown that less than 25% of benign nodules shrink more than 50% with TSH suppression in iodine-replete populations. Thyroidectomy should be performed if a nodule enlarges on TSH suppression, causes compressive symptoms, or for cos-metic reasons. An exception to this general rule is the patient who has had previous irradiation of the thyroid gland or has a family history of thyroid cancer. In these patients, total or near-total thyroidectomy is recommended because of the high incidence of thyroid cancer and decreased reliability of FNAB in this setting.Malignant Thyroid DiseaseIn the United States, thyroid cancer accounts for <1% of all malignancies (2% of women and 0.5% of men) and is the most rapidly increasing cancer in women. Thyroid cancer is respon-sible for six deaths per million persons annually. Most patients present with a palpable swelling in the neck, which initiates |
Surgery_Schwartz_10843 | Surgery_Schwartz | is the most rapidly increasing cancer in women. Thyroid cancer is respon-sible for six deaths per million persons annually. Most patients present with a palpable swelling in the neck, which initiates assessment through a combination of history, physical exami-nation, and FNAB.Molecular Genetics of Thyroid Tumorigenesis. Several oncogenes and tumor suppressor genes are involved in thy-roid tumorigenesis,22 as depicted in Table 38-5. The RET proto-oncogene (Fig. 38-15) plays a significant role in the pathogenesis of thyroid cancers. It is located on chromosome 10 and encodes a receptor tyrosine kinase, which binds sev-eral growth factors such as glial-derived neurotrophic factor and neurturin. The RET protein is expressed in tissues derived from the embryonic nervous and excretory systems. Therefore, Table 38-5Oncogenes, tumor suppressor genes, and other genetic alterations implicated in thyroid tumorigenesisGENEFUNCTIONTUMOROncogenes RETMembrane receptor with tyrosine kinase | Surgery_Schwartz. is the most rapidly increasing cancer in women. Thyroid cancer is respon-sible for six deaths per million persons annually. Most patients present with a palpable swelling in the neck, which initiates assessment through a combination of history, physical exami-nation, and FNAB.Molecular Genetics of Thyroid Tumorigenesis. Several oncogenes and tumor suppressor genes are involved in thy-roid tumorigenesis,22 as depicted in Table 38-5. The RET proto-oncogene (Fig. 38-15) plays a significant role in the pathogenesis of thyroid cancers. It is located on chromosome 10 and encodes a receptor tyrosine kinase, which binds sev-eral growth factors such as glial-derived neurotrophic factor and neurturin. The RET protein is expressed in tissues derived from the embryonic nervous and excretory systems. Therefore, Table 38-5Oncogenes, tumor suppressor genes, and other genetic alterations implicated in thyroid tumorigenesisGENEFUNCTIONTUMOROncogenes RETMembrane receptor with tyrosine kinase |
Surgery_Schwartz_10844 | Surgery_Schwartz | Therefore, Table 38-5Oncogenes, tumor suppressor genes, and other genetic alterations implicated in thyroid tumorigenesisGENEFUNCTIONTUMOROncogenes RETMembrane receptor with tyrosine kinase activitySporadic and familial MTC, PTC (RET/PTC rearrangements)METSameOverexpressed in PTCTRK1SameActivated in some PTCTSH-RLinked to heterotrimeric G proteinHyperfunctioning adenomaGsα (gsp)Signal transduction molecule (GTP binding)Hyperfunctioning adenoma, follicular adenomaRasSignal transduction proteinFollicular adenoma and carcinoma, PTCPAX8/PPARγ1OncoproteinFollicular adenoma, follicular carcinomaB-Raf (BRAF)Signal transductionPTC, tall cell and poorly differentiated, anaplasticCTNNB1 (β-catenin)Signal transductionUpregulated in poorly differentiated and anaplastic cancersTERT promoterChromosome integrityMutated in thyroid cancers including PTC, FTC and anaplastic cancersTumor suppressors p53Cell cycle regulator, arrests cells in G1, induces apoptosisDedifferentiated PTC, FTC, anaplastic | Surgery_Schwartz. Therefore, Table 38-5Oncogenes, tumor suppressor genes, and other genetic alterations implicated in thyroid tumorigenesisGENEFUNCTIONTUMOROncogenes RETMembrane receptor with tyrosine kinase activitySporadic and familial MTC, PTC (RET/PTC rearrangements)METSameOverexpressed in PTCTRK1SameActivated in some PTCTSH-RLinked to heterotrimeric G proteinHyperfunctioning adenomaGsα (gsp)Signal transduction molecule (GTP binding)Hyperfunctioning adenoma, follicular adenomaRasSignal transduction proteinFollicular adenoma and carcinoma, PTCPAX8/PPARγ1OncoproteinFollicular adenoma, follicular carcinomaB-Raf (BRAF)Signal transductionPTC, tall cell and poorly differentiated, anaplasticCTNNB1 (β-catenin)Signal transductionUpregulated in poorly differentiated and anaplastic cancersTERT promoterChromosome integrityMutated in thyroid cancers including PTC, FTC and anaplastic cancersTumor suppressors p53Cell cycle regulator, arrests cells in G1, induces apoptosisDedifferentiated PTC, FTC, anaplastic |
Surgery_Schwartz_10845 | Surgery_Schwartz | integrityMutated in thyroid cancers including PTC, FTC and anaplastic cancersTumor suppressors p53Cell cycle regulator, arrests cells in G1, induces apoptosisDedifferentiated PTC, FTC, anaplastic cancersp16Cell cycle regulator, inhibits cyclin-dependent kinaseThyroid cancer cell linesPTENProtein tyrosine phosphataseFollicular adenoma and carcinomaOther genetic alterations microRNASmall, noncoding RNASpecific types upregulated in papillary and some follicular carcinomasFTC = follicular thyroid cancer; GTP = guanosine triphosphate; MTC = medullary thyroid cancer; PTC = papillary thyroid cancer.Brunicardi_Ch38_p1625-p1704.indd 164501/03/19 11:20 AM 1646SPECIFIC CONSIDERATIONSPART IIReceptorGDNFTyrosinekinaseIntracellularExtracellularSubstrateATP620618811609634830804768= MEN2A & FMTC mutation= MEN2B mutation= FMTC mutation= Hirschsprung's disease mutation918Figure 38-15. Structure of the RET tyrosine kinase receptor. Multiple endocrine neoplasia type 2A (MEN2A) and type 2B | Surgery_Schwartz. integrityMutated in thyroid cancers including PTC, FTC and anaplastic cancersTumor suppressors p53Cell cycle regulator, arrests cells in G1, induces apoptosisDedifferentiated PTC, FTC, anaplastic cancersp16Cell cycle regulator, inhibits cyclin-dependent kinaseThyroid cancer cell linesPTENProtein tyrosine phosphataseFollicular adenoma and carcinomaOther genetic alterations microRNASmall, noncoding RNASpecific types upregulated in papillary and some follicular carcinomasFTC = follicular thyroid cancer; GTP = guanosine triphosphate; MTC = medullary thyroid cancer; PTC = papillary thyroid cancer.Brunicardi_Ch38_p1625-p1704.indd 164501/03/19 11:20 AM 1646SPECIFIC CONSIDERATIONSPART IIReceptorGDNFTyrosinekinaseIntracellularExtracellularSubstrateATP620618811609634830804768= MEN2A & FMTC mutation= MEN2B mutation= FMTC mutation= Hirschsprung's disease mutation918Figure 38-15. Structure of the RET tyrosine kinase receptor. Multiple endocrine neoplasia type 2A (MEN2A) and type 2B |
Surgery_Schwartz_10846 | Surgery_Schwartz | mutation= MEN2B mutation= FMTC mutation= Hirschsprung's disease mutation918Figure 38-15. Structure of the RET tyrosine kinase receptor. Multiple endocrine neoplasia type 2A (MEN2A) and type 2B (MEN2B), famil-ial medullary thyroid cancer (FMTC), and Hirschsprung’s disease result from germline mutations in the RET proto-oncogene. The extracel-lular domain binds the ligand glial-derived neurotrophic factor (GDNF) and contains 28 cysteine residues. Mutations in cysteine residues at codons 609, 611, 618, 620, and 634, which are in the juxtamembrane region of the receptor, are associated with MEN2A and FMTC. The ATP-binding site is located intracellularly near the site, which binds the substrate for the tyrosine kinase catalytic domain. Mutations at codon 918 (Met to Thr) alter the substrate binding pocket located in the intracellular region and cause MEN2B. FMTC is associated with mutations at codons 768 and 804. ATP = adenosine triphosphate. (Reproduced with permission from Wells S, | Surgery_Schwartz. mutation= MEN2B mutation= FMTC mutation= Hirschsprung's disease mutation918Figure 38-15. Structure of the RET tyrosine kinase receptor. Multiple endocrine neoplasia type 2A (MEN2A) and type 2B (MEN2B), famil-ial medullary thyroid cancer (FMTC), and Hirschsprung’s disease result from germline mutations in the RET proto-oncogene. The extracel-lular domain binds the ligand glial-derived neurotrophic factor (GDNF) and contains 28 cysteine residues. Mutations in cysteine residues at codons 609, 611, 618, 620, and 634, which are in the juxtamembrane region of the receptor, are associated with MEN2A and FMTC. The ATP-binding site is located intracellularly near the site, which binds the substrate for the tyrosine kinase catalytic domain. Mutations at codon 918 (Met to Thr) alter the substrate binding pocket located in the intracellular region and cause MEN2B. FMTC is associated with mutations at codons 768 and 804. ATP = adenosine triphosphate. (Reproduced with permission from Wells S, |
Surgery_Schwartz_10847 | Surgery_Schwartz | binding pocket located in the intracellular region and cause MEN2B. FMTC is associated with mutations at codons 768 and 804. ATP = adenosine triphosphate. (Reproduced with permission from Wells S, Franz C. Medullary carcinoma of the thyroid gland, World J Surg. 2000 Aug;24(8):952-956.)RET disruption can lead to developmental abnormalities in organs derived from these systems, such as the enteric nervous system (Hirschsprung’s disease) and kidney. Germline muta-tions in the RET proto-oncogene are known to predispose to MEN2A, MEN2B, and familial MTCs, and somatic mutations have been demonstrated in tumors derived from the neural crest, such as MTCs (30%) and pheochromocytomas. The tyrosine kinase domain of RET can fuse with other genes by rearrange-ment. These fusion products also function as oncogenes and have been implicated in the pathogenesis of PTCs. At least 15 RET/PTC rearrangements have been described and appear to be early events in tumorigenesis. Young age and radiation | Surgery_Schwartz. binding pocket located in the intracellular region and cause MEN2B. FMTC is associated with mutations at codons 768 and 804. ATP = adenosine triphosphate. (Reproduced with permission from Wells S, Franz C. Medullary carcinoma of the thyroid gland, World J Surg. 2000 Aug;24(8):952-956.)RET disruption can lead to developmental abnormalities in organs derived from these systems, such as the enteric nervous system (Hirschsprung’s disease) and kidney. Germline muta-tions in the RET proto-oncogene are known to predispose to MEN2A, MEN2B, and familial MTCs, and somatic mutations have been demonstrated in tumors derived from the neural crest, such as MTCs (30%) and pheochromocytomas. The tyrosine kinase domain of RET can fuse with other genes by rearrange-ment. These fusion products also function as oncogenes and have been implicated in the pathogenesis of PTCs. At least 15 RET/PTC rearrangements have been described and appear to be early events in tumorigenesis. Young age and radiation |
Surgery_Schwartz_10848 | Surgery_Schwartz | as oncogenes and have been implicated in the pathogenesis of PTCs. At least 15 RET/PTC rearrangements have been described and appear to be early events in tumorigenesis. Young age and radiation expo-sure seem to be independent risk factors for the development of RET/PTC rearrangements. Up to 70% of papillary cancers in children exposed to the radiation fallout from the 1986 Cher-nobyl disaster carry RET/PTC rearrangements, the most com-mon being RET/PTC1 and RET/PTC3. These rearrangements confer constitutive activation of the receptor tyrosine kinases. RET/PTC3 is associated with a solid type of PTC that appears to present at a higher stage and to be more aggressive. It has now been established that RET/PTC signaling involves the mitogen-activated protein kinase (MAPK) pathway via other signaling molecules such as Ras, Raf, and MEK. In normal cells, physi-ologic activation of Raf kinases occurs via direct interaction with guanosine triphosphate (GTP)–bound Ras, a membrane-bound small | Surgery_Schwartz. as oncogenes and have been implicated in the pathogenesis of PTCs. At least 15 RET/PTC rearrangements have been described and appear to be early events in tumorigenesis. Young age and radiation expo-sure seem to be independent risk factors for the development of RET/PTC rearrangements. Up to 70% of papillary cancers in children exposed to the radiation fallout from the 1986 Cher-nobyl disaster carry RET/PTC rearrangements, the most com-mon being RET/PTC1 and RET/PTC3. These rearrangements confer constitutive activation of the receptor tyrosine kinases. RET/PTC3 is associated with a solid type of PTC that appears to present at a higher stage and to be more aggressive. It has now been established that RET/PTC signaling involves the mitogen-activated protein kinase (MAPK) pathway via other signaling molecules such as Ras, Raf, and MEK. In normal cells, physi-ologic activation of Raf kinases occurs via direct interaction with guanosine triphosphate (GTP)–bound Ras, a membrane-bound small |
Surgery_Schwartz_10849 | Surgery_Schwartz | molecules such as Ras, Raf, and MEK. In normal cells, physi-ologic activation of Raf kinases occurs via direct interaction with guanosine triphosphate (GTP)–bound Ras, a membrane-bound small G protein. Activated Raf, a serine-threonine kinase, in turn phosphorylates MEK, another serine-threonine kinase. This leads to phosphorylation of ERK/MAPK, which phosphor-ylates regulatory molecules in the nucleus, thereby altering gene expression. Aberrant activation of the MAPK pathway leads to tumorigenesis. Aside from RET/PTC alterations, mutations in the Ras genes can also activate the MAPK pathway. Mutated RAS oncogenes have been identified in up to 20% to 40% of thyroid follicular adenomas and carcinomas, multinodular goi-ters, and papillary and anaplastic carcinomas. There are three Raf kinases, A-Raf, B-Raf (BRAF), and C-Raf. Mutations in BRAF also have been implicated in aberrant MAPK pathway activation and tumorigenesis. Of the various identified BRAF mutations, T1799A (V600E amino | Surgery_Schwartz. molecules such as Ras, Raf, and MEK. In normal cells, physi-ologic activation of Raf kinases occurs via direct interaction with guanosine triphosphate (GTP)–bound Ras, a membrane-bound small G protein. Activated Raf, a serine-threonine kinase, in turn phosphorylates MEK, another serine-threonine kinase. This leads to phosphorylation of ERK/MAPK, which phosphor-ylates regulatory molecules in the nucleus, thereby altering gene expression. Aberrant activation of the MAPK pathway leads to tumorigenesis. Aside from RET/PTC alterations, mutations in the Ras genes can also activate the MAPK pathway. Mutated RAS oncogenes have been identified in up to 20% to 40% of thyroid follicular adenomas and carcinomas, multinodular goi-ters, and papillary and anaplastic carcinomas. There are three Raf kinases, A-Raf, B-Raf (BRAF), and C-Raf. Mutations in BRAF also have been implicated in aberrant MAPK pathway activation and tumorigenesis. Of the various identified BRAF mutations, T1799A (V600E amino |
Surgery_Schwartz_10850 | Surgery_Schwartz | A-Raf, B-Raf (BRAF), and C-Raf. Mutations in BRAF also have been implicated in aberrant MAPK pathway activation and tumorigenesis. Of the various identified BRAF mutations, T1799A (V600E amino acid substitution) is the most common and occurs frequently in thyroid cancers. Interestingly, BRAF mutations occur in papillary and anaplastic tumors (aver-age prevalence of 44% and 22%, respectively),23 but not in fol-licular thyroid cancers, suggesting a role in the pathogenesis of these malignancies. Studies also show that BRAF mutations are associated with more aggressive clinicopathologic features, including larger tumor size, invasion, and lymphadenopathy, and may have a role as prognostic markers.The p53 gene is a tumor suppressor gene encoding a transcriptional regulator, which causes cell cycle arrest allow-ing repair of damaged DNA, thus helping to maintain genomic integrity. Mutations of p53 are rare in PTCs but common in undifferentiated thyroid cancers and thyroid cancer cell | Surgery_Schwartz. A-Raf, B-Raf (BRAF), and C-Raf. Mutations in BRAF also have been implicated in aberrant MAPK pathway activation and tumorigenesis. Of the various identified BRAF mutations, T1799A (V600E amino acid substitution) is the most common and occurs frequently in thyroid cancers. Interestingly, BRAF mutations occur in papillary and anaplastic tumors (aver-age prevalence of 44% and 22%, respectively),23 but not in fol-licular thyroid cancers, suggesting a role in the pathogenesis of these malignancies. Studies also show that BRAF mutations are associated with more aggressive clinicopathologic features, including larger tumor size, invasion, and lymphadenopathy, and may have a role as prognostic markers.The p53 gene is a tumor suppressor gene encoding a transcriptional regulator, which causes cell cycle arrest allow-ing repair of damaged DNA, thus helping to maintain genomic integrity. Mutations of p53 are rare in PTCs but common in undifferentiated thyroid cancers and thyroid cancer cell |
Surgery_Schwartz_10851 | Surgery_Schwartz | cell cycle arrest allow-ing repair of damaged DNA, thus helping to maintain genomic integrity. Mutations of p53 are rare in PTCs but common in undifferentiated thyroid cancers and thyroid cancer cell lines. Other cell cycle regulators and tumor suppressors such as p15 and p16 are mutated more commonly in thyroid cancer cell lines than in primary tumors. An oncogene resulting from the fusion of the DNA binding domain of the thyroid-transcription fac-tor PAX8 gene to the peroxisome proliferator-activated receptor gamma 1 (PPARγ1) has been noted to play an important role Brunicardi_Ch38_p1625-p1704.indd 164601/03/19 11:21 AM 1647THYROID, PARATHYROID, AND ADRENALCHAPTER 38in the development of follicular neoplasms, including follicular cancers. Mutations in the telomerase reverse transcriptase cata-lytic subunit (TERT) promoter unit have also been recently been identified in well-differentiated thyroid cancers and appear to be related to poor prognosis. Thyroid cancer stem cells have | Surgery_Schwartz. cell cycle arrest allow-ing repair of damaged DNA, thus helping to maintain genomic integrity. Mutations of p53 are rare in PTCs but common in undifferentiated thyroid cancers and thyroid cancer cell lines. Other cell cycle regulators and tumor suppressors such as p15 and p16 are mutated more commonly in thyroid cancer cell lines than in primary tumors. An oncogene resulting from the fusion of the DNA binding domain of the thyroid-transcription fac-tor PAX8 gene to the peroxisome proliferator-activated receptor gamma 1 (PPARγ1) has been noted to play an important role Brunicardi_Ch38_p1625-p1704.indd 164601/03/19 11:21 AM 1647THYROID, PARATHYROID, AND ADRENALCHAPTER 38in the development of follicular neoplasms, including follicular cancers. Mutations in the telomerase reverse transcriptase cata-lytic subunit (TERT) promoter unit have also been recently been identified in well-differentiated thyroid cancers and appear to be related to poor prognosis. Thyroid cancer stem cells have |
Surgery_Schwartz_10852 | Surgery_Schwartz | cata-lytic subunit (TERT) promoter unit have also been recently been identified in well-differentiated thyroid cancers and appear to be related to poor prognosis. Thyroid cancer stem cells have also been identified; however, their role in thyroid carcinogenesis remains to be determined.24 Mutations in the kinases PIK3CA and AKT1 are rare in thyroid cancers and tend to occur as late events in tumorigenesis.Specific Tumor Types Papillary Carcinoma Papillary carcinoma accounts for 80% of all thyroid malignancies in iodine-sufficient areas and is the predominant thyroid cancer in children and individuals exposed to external radiation. Papillary carcinoma occurs more often in women, with a 2:1 female-to-male ratio, and the mean age at presentation is 30 to 40 years. Most patients are euthyroid and present with a slow-growing painless mass in the neck. Dys-phagia, dyspnea, and dysphonia usually are associated with locally advanced invasive disease. Lymph node metastases are common, | Surgery_Schwartz. cata-lytic subunit (TERT) promoter unit have also been recently been identified in well-differentiated thyroid cancers and appear to be related to poor prognosis. Thyroid cancer stem cells have also been identified; however, their role in thyroid carcinogenesis remains to be determined.24 Mutations in the kinases PIK3CA and AKT1 are rare in thyroid cancers and tend to occur as late events in tumorigenesis.Specific Tumor Types Papillary Carcinoma Papillary carcinoma accounts for 80% of all thyroid malignancies in iodine-sufficient areas and is the predominant thyroid cancer in children and individuals exposed to external radiation. Papillary carcinoma occurs more often in women, with a 2:1 female-to-male ratio, and the mean age at presentation is 30 to 40 years. Most patients are euthyroid and present with a slow-growing painless mass in the neck. Dys-phagia, dyspnea, and dysphonia usually are associated with locally advanced invasive disease. Lymph node metastases are common, |
Surgery_Schwartz_10853 | Surgery_Schwartz | and present with a slow-growing painless mass in the neck. Dys-phagia, dyspnea, and dysphonia usually are associated with locally advanced invasive disease. Lymph node metastases are common, especially in children and young adults, and may be the presenting complaint. “Lateral aberrant thyroid” almost always denotes a cervical lymph node that has been invaded by metastatic cancer. Suspicion of thyroid cancer often originates through physical examination of patients and a review of their history. Diagnosis is established by FNAB of the thyroid mass or lymph node. Once thyroid cancer is diagnosed on FNAB, a complete neck ultrasound is strongly recommended to evalu-ate the contralateral lobe and for lymph node metastases in the central and lateral neck compartments. Distant metastases are uncommon at initial presentation, but may ultimately develop in up to 20% of patients. The most common sites are lungs, fol-lowed by bone, liver, and brain.Pathology. On gross examination, PTCs | Surgery_Schwartz. and present with a slow-growing painless mass in the neck. Dys-phagia, dyspnea, and dysphonia usually are associated with locally advanced invasive disease. Lymph node metastases are common, especially in children and young adults, and may be the presenting complaint. “Lateral aberrant thyroid” almost always denotes a cervical lymph node that has been invaded by metastatic cancer. Suspicion of thyroid cancer often originates through physical examination of patients and a review of their history. Diagnosis is established by FNAB of the thyroid mass or lymph node. Once thyroid cancer is diagnosed on FNAB, a complete neck ultrasound is strongly recommended to evalu-ate the contralateral lobe and for lymph node metastases in the central and lateral neck compartments. Distant metastases are uncommon at initial presentation, but may ultimately develop in up to 20% of patients. The most common sites are lungs, fol-lowed by bone, liver, and brain.Pathology. On gross examination, PTCs |
Surgery_Schwartz_10854 | Surgery_Schwartz | are uncommon at initial presentation, but may ultimately develop in up to 20% of patients. The most common sites are lungs, fol-lowed by bone, liver, and brain.Pathology. On gross examination, PTCs generally are hard and whitish and remain flat on sectioning with a blade, in contrast to normal tissue or benign nodular lesions that tend to bulge. Mac-roscopic calcification, necrosis, or cystic change may be appar-ent. Histologically, papillary carcinomas may exhibit papillary projections (Fig. 38-16A), a mixed pattern of papillary and fol-licular structures, or a pure follicular pattern (follicular variant). The diagnosis is established by characteristic nuclear cellular features. Cells are cuboidal with pale, abundant cytoplasm, crowded nuclei that may demonstrate “grooving,” and intranu-clear cytoplasmic inclusions (leading to the designation of Orphan Annie nuclei [Fig. 38-16B]), which allow diagnosis by FNAB. Psammoma bodies, which are microscopic, calcified deposits representing | Surgery_Schwartz. are uncommon at initial presentation, but may ultimately develop in up to 20% of patients. The most common sites are lungs, fol-lowed by bone, liver, and brain.Pathology. On gross examination, PTCs generally are hard and whitish and remain flat on sectioning with a blade, in contrast to normal tissue or benign nodular lesions that tend to bulge. Mac-roscopic calcification, necrosis, or cystic change may be appar-ent. Histologically, papillary carcinomas may exhibit papillary projections (Fig. 38-16A), a mixed pattern of papillary and fol-licular structures, or a pure follicular pattern (follicular variant). The diagnosis is established by characteristic nuclear cellular features. Cells are cuboidal with pale, abundant cytoplasm, crowded nuclei that may demonstrate “grooving,” and intranu-clear cytoplasmic inclusions (leading to the designation of Orphan Annie nuclei [Fig. 38-16B]), which allow diagnosis by FNAB. Psammoma bodies, which are microscopic, calcified deposits representing |
Surgery_Schwartz_10855 | Surgery_Schwartz | cytoplasmic inclusions (leading to the designation of Orphan Annie nuclei [Fig. 38-16B]), which allow diagnosis by FNAB. Psammoma bodies, which are microscopic, calcified deposits representing clumps of sloughed cells, also may be present. Mixed papillary-follicular tumors and follicular variant of papillary thyroid carcinoma (FVPTC) are classified as papil-lary carcinomas because they behave biologically as papillary carcinomas. Two main subtypes of FVPTC are recognized: encapsulated and nonencapsulated (infiltrative). The for-mer is challenging to diagnose. Since the tumors have no invasion, the diagnosis relies on the finding of characteristic nuclei, which can be subjective. In addition, several studies have shown that the encapsulated tumors have an indolent behavior and are genetically distinct from their infiltrative counterparts. As such, these tumors are now designated noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).25 Multifocality is | Surgery_Schwartz. cytoplasmic inclusions (leading to the designation of Orphan Annie nuclei [Fig. 38-16B]), which allow diagnosis by FNAB. Psammoma bodies, which are microscopic, calcified deposits representing clumps of sloughed cells, also may be present. Mixed papillary-follicular tumors and follicular variant of papillary thyroid carcinoma (FVPTC) are classified as papil-lary carcinomas because they behave biologically as papillary carcinomas. Two main subtypes of FVPTC are recognized: encapsulated and nonencapsulated (infiltrative). The for-mer is challenging to diagnose. Since the tumors have no invasion, the diagnosis relies on the finding of characteristic nuclei, which can be subjective. In addition, several studies have shown that the encapsulated tumors have an indolent behavior and are genetically distinct from their infiltrative counterparts. As such, these tumors are now designated noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).25 Multifocality is |
Surgery_Schwartz_10856 | Surgery_Schwartz | distinct from their infiltrative counterparts. As such, these tumors are now designated noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).25 Multifocality is common in papillary carcinoma and may be present in up to 85% of cases on microscopic examination. Mul-tifocality is associated with an increased risk of cervical nodal metastases, and these tumors may rarely invade adjacent struc-tures such as the trachea, esophagus, and RLNs. Other variants of papillary carcinoma include tall cell, insular, columnar, dif-fuse sclerosing, clear cell, trabecular, and poorly differentiated types. These variants account for about 1% of all papillary car-cinomas and are generally associated with a worse prognosis.Minimal or occult/microcarcinoma refers to tumors of 1 cm or less in size with no evidence of local invasiveness through the thyroid capsule or angioinvasion, and that are not associated with lymph node metastases. They are nonpalpable and usually are | Surgery_Schwartz. distinct from their infiltrative counterparts. As such, these tumors are now designated noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).25 Multifocality is common in papillary carcinoma and may be present in up to 85% of cases on microscopic examination. Mul-tifocality is associated with an increased risk of cervical nodal metastases, and these tumors may rarely invade adjacent struc-tures such as the trachea, esophagus, and RLNs. Other variants of papillary carcinoma include tall cell, insular, columnar, dif-fuse sclerosing, clear cell, trabecular, and poorly differentiated types. These variants account for about 1% of all papillary car-cinomas and are generally associated with a worse prognosis.Minimal or occult/microcarcinoma refers to tumors of 1 cm or less in size with no evidence of local invasiveness through the thyroid capsule or angioinvasion, and that are not associated with lymph node metastases. They are nonpalpable and usually are |
Surgery_Schwartz_10857 | Surgery_Schwartz | 1 cm or less in size with no evidence of local invasiveness through the thyroid capsule or angioinvasion, and that are not associated with lymph node metastases. They are nonpalpable and usually are incidental findings at operative, histologic, or autopsy examination. Studies have demonstrated occult PTC to be present in 2% to 36% of thyroid glands removed at autopsy. These tumors are also being identified more frequently due to the widespread use of ultrasound. These occult tumors are generally associated with a better prognosis than larger tumors, but they may be more aggressive than previously appreciated. About 25% of patients with these tumors have associated occult lymph node metastases.Prognostic Indicators. In general, patients with PTC have an excellent prognosis with a >95% 10-year survival rate. Sev-eral prognostic indicators have been incorporated into various 4Figure 38-16. A. Histomicrograph of a papillary thyroid cancer (hematoxylin-eosin stain). B. Fine-needle | Surgery_Schwartz. 1 cm or less in size with no evidence of local invasiveness through the thyroid capsule or angioinvasion, and that are not associated with lymph node metastases. They are nonpalpable and usually are incidental findings at operative, histologic, or autopsy examination. Studies have demonstrated occult PTC to be present in 2% to 36% of thyroid glands removed at autopsy. These tumors are also being identified more frequently due to the widespread use of ultrasound. These occult tumors are generally associated with a better prognosis than larger tumors, but they may be more aggressive than previously appreciated. About 25% of patients with these tumors have associated occult lymph node metastases.Prognostic Indicators. In general, patients with PTC have an excellent prognosis with a >95% 10-year survival rate. Sev-eral prognostic indicators have been incorporated into various 4Figure 38-16. A. Histomicrograph of a papillary thyroid cancer (hematoxylin-eosin stain). B. Fine-needle |
Surgery_Schwartz_10858 | Surgery_Schwartz | 10-year survival rate. Sev-eral prognostic indicators have been incorporated into various 4Figure 38-16. A. Histomicrograph of a papillary thyroid cancer (hematoxylin-eosin stain). B. Fine-needle aspiration biopsy specimen from a papillary thyroid cancer showing typical intranuclear cytoplasmic inclusions in the center of the slide.Brunicardi_Ch38_p1625-p1704.indd 164701/03/19 11:21 AM 1648SPECIFIC CONSIDERATIONSPART IIstaging systems, which enable patients to be stratified into low-risk and high-risk groups. Unfortunately, all of these classifica-tion systems rely on data that are not available preoperatively.In 1987, Hay and colleagues26 at the Mayo Clinic proposed the AGES scoring system, which incorporates Age, histologic Grade, Extrathyroidal invasion, and metastases and tumor Size to predict the risk of dying from papillary cancer. Low-risk patients are young, with well-differentiated tumors, no metas-tases, and small primary lesions, whereas high-risk patients are older, | Surgery_Schwartz. 10-year survival rate. Sev-eral prognostic indicators have been incorporated into various 4Figure 38-16. A. Histomicrograph of a papillary thyroid cancer (hematoxylin-eosin stain). B. Fine-needle aspiration biopsy specimen from a papillary thyroid cancer showing typical intranuclear cytoplasmic inclusions in the center of the slide.Brunicardi_Ch38_p1625-p1704.indd 164701/03/19 11:21 AM 1648SPECIFIC CONSIDERATIONSPART IIstaging systems, which enable patients to be stratified into low-risk and high-risk groups. Unfortunately, all of these classifica-tion systems rely on data that are not available preoperatively.In 1987, Hay and colleagues26 at the Mayo Clinic proposed the AGES scoring system, which incorporates Age, histologic Grade, Extrathyroidal invasion, and metastases and tumor Size to predict the risk of dying from papillary cancer. Low-risk patients are young, with well-differentiated tumors, no metas-tases, and small primary lesions, whereas high-risk patients are older, |
Surgery_Schwartz_10859 | Surgery_Schwartz | Size to predict the risk of dying from papillary cancer. Low-risk patients are young, with well-differentiated tumors, no metas-tases, and small primary lesions, whereas high-risk patients are older, with poorly differentiated tumors, local invasion, dis-tant metastases, and large primary lesions. The MACIS scale is a postoperative system modified from the AGES scale. This scale incorporates distant Metastases, Age at presentation (<40 or >40 years old), Completeness of original surgical resection, extrathyroidal Invasion, and Size of original lesion (in centime-ters) and classifies patients into four risk groups based on their scores. Cady proposed the AMES system27 to classify differen-tiated thyroid tumors into lowand high-risk groups using Age (men <40 years old, women <50 years old), Metastases, Extra-thyroidal spread, and Size of tumors (< or >5 cm). A simplified system by DeGroot and associates28 uses four groups—class I (intrathyroidal), class II (cervical nodal metastases), | Surgery_Schwartz. Size to predict the risk of dying from papillary cancer. Low-risk patients are young, with well-differentiated tumors, no metas-tases, and small primary lesions, whereas high-risk patients are older, with poorly differentiated tumors, local invasion, dis-tant metastases, and large primary lesions. The MACIS scale is a postoperative system modified from the AGES scale. This scale incorporates distant Metastases, Age at presentation (<40 or >40 years old), Completeness of original surgical resection, extrathyroidal Invasion, and Size of original lesion (in centime-ters) and classifies patients into four risk groups based on their scores. Cady proposed the AMES system27 to classify differen-tiated thyroid tumors into lowand high-risk groups using Age (men <40 years old, women <50 years old), Metastases, Extra-thyroidal spread, and Size of tumors (< or >5 cm). A simplified system by DeGroot and associates28 uses four groups—class I (intrathyroidal), class II (cervical nodal metastases), |
Surgery_Schwartz_10860 | Surgery_Schwartz | Metastases, Extra-thyroidal spread, and Size of tumors (< or >5 cm). A simplified system by DeGroot and associates28 uses four groups—class I (intrathyroidal), class II (cervical nodal metastases), class III (extrathyroidal invasion), and class IV (distant metastases)—to determine prognosis. Another classification system is the TNM system (Tumor, Nodal status, Metastases; Table 38-6), which used by most medical centers in North America and has been recently updated.29 In this new version, minimal extrathyroidal extension is no longer considered T3a disease. Thyroglobulin doubling time (using levels obtained when TSH is <0.1 mIU/L) has also been demonstrated to be an independent prognostic marker for metastatic disease and recurrence.30Several molecular and genetic markers such as tumor DNA aneuploidy, decreased cyclic adenosine monophosphate response to TSH, increased epidermal growth factor binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence of p53 | Surgery_Schwartz. Metastases, Extra-thyroidal spread, and Size of tumors (< or >5 cm). A simplified system by DeGroot and associates28 uses four groups—class I (intrathyroidal), class II (cervical nodal metastases), class III (extrathyroidal invasion), and class IV (distant metastases)—to determine prognosis. Another classification system is the TNM system (Tumor, Nodal status, Metastases; Table 38-6), which used by most medical centers in North America and has been recently updated.29 In this new version, minimal extrathyroidal extension is no longer considered T3a disease. Thyroglobulin doubling time (using levels obtained when TSH is <0.1 mIU/L) has also been demonstrated to be an independent prognostic marker for metastatic disease and recurrence.30Several molecular and genetic markers such as tumor DNA aneuploidy, decreased cyclic adenosine monophosphate response to TSH, increased epidermal growth factor binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence of p53 |
Surgery_Schwartz_10861 | Surgery_Schwartz | DNA aneuploidy, decreased cyclic adenosine monophosphate response to TSH, increased epidermal growth factor binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence of p53 mutations also have been associated with a worse prognosis. The presence of BRAF V600E mutation, as previously mentioned, is associated with aggressive tumor characteristics, including extrathyroidal extension, older age at presentation, and lymph node and distant metastases. This muta-tion also appears to be an independent predictor of both tumor recurrence (even for early-stage disease) and tumor-related mortality. Some studies propose that BRAF mutation status on FNAB can be used to tailor initial management including more extensive initial surgical excision, high-dose postoperative RAI therapy, increased TSH suppression, and closer follow-up.31 The correlation of RET/PTC rearrangements and Ras mutations with prognosis is less clear. TERT promoter mutations have been associated with | Surgery_Schwartz. DNA aneuploidy, decreased cyclic adenosine monophosphate response to TSH, increased epidermal growth factor binding, presence of N-ras and gsp mutations, overexpression of c-myc, and presence of p53 mutations also have been associated with a worse prognosis. The presence of BRAF V600E mutation, as previously mentioned, is associated with aggressive tumor characteristics, including extrathyroidal extension, older age at presentation, and lymph node and distant metastases. This muta-tion also appears to be an independent predictor of both tumor recurrence (even for early-stage disease) and tumor-related mortality. Some studies propose that BRAF mutation status on FNAB can be used to tailor initial management including more extensive initial surgical excision, high-dose postoperative RAI therapy, increased TSH suppression, and closer follow-up.31 The correlation of RET/PTC rearrangements and Ras mutations with prognosis is less clear. TERT promoter mutations have been associated with |
Surgery_Schwartz_10862 | Surgery_Schwartz | therapy, increased TSH suppression, and closer follow-up.31 The correlation of RET/PTC rearrangements and Ras mutations with prognosis is less clear. TERT promoter mutations have been associated with poor disease-specific and disease-free survival.Surgical Treatment. Most authors agree that patients with high-risk tumors (judged by any of the classification systems discussed earlier in “Prognostic Indicators”) or bilateral tumors should undergo total or near-total thyroidectomy. The optimal surgical strategy in the majority of patients with low-risk (small, unilateral) cancers was controversial for many years, with the focus of the debate centering around outcome data and risks associated with extent of thyroidectomy in this group of patients. Proponents of total thyroidectomy indicate that it enables the use of RAI to effectively detect and treat residual thyroid tissue or metastatic disease and makes serum Tg level a more sensitive marker of recurrent or persistent disease. It is | Surgery_Schwartz. therapy, increased TSH suppression, and closer follow-up.31 The correlation of RET/PTC rearrangements and Ras mutations with prognosis is less clear. TERT promoter mutations have been associated with poor disease-specific and disease-free survival.Surgical Treatment. Most authors agree that patients with high-risk tumors (judged by any of the classification systems discussed earlier in “Prognostic Indicators”) or bilateral tumors should undergo total or near-total thyroidectomy. The optimal surgical strategy in the majority of patients with low-risk (small, unilateral) cancers was controversial for many years, with the focus of the debate centering around outcome data and risks associated with extent of thyroidectomy in this group of patients. Proponents of total thyroidectomy indicate that it enables the use of RAI to effectively detect and treat residual thyroid tissue or metastatic disease and makes serum Tg level a more sensitive marker of recurrent or persistent disease. It is |
Surgery_Schwartz_10863 | Surgery_Schwartz | that it enables the use of RAI to effectively detect and treat residual thyroid tissue or metastatic disease and makes serum Tg level a more sensitive marker of recurrent or persistent disease. It is also known that a significant proportion (33% to 50%) of patients who develop a recurrence die from their disease,32 and even though the data are retrospective, long-term, follow-up studies suggest that recur-rence rates are lowered and that survival is improved in patients undergoing near-total or total thyroidectomy28,32-36 (Fig. 38-17). In addition, diminished survival is noted in patients with low-risk disease (mortality rates of 5% at 10 to 20 years), and it is not possible to accurately risk stratify patients preoperatively. In the last 10 years, a large study of >50,000 patients with papillary cancer demonstrated that, in multivariate analyses, total thyroid-ectomy led to a significantly improved recurrence and survival for tumors >1 cm. Furthermore, the authors also showed that | Surgery_Schwartz. that it enables the use of RAI to effectively detect and treat residual thyroid tissue or metastatic disease and makes serum Tg level a more sensitive marker of recurrent or persistent disease. It is also known that a significant proportion (33% to 50%) of patients who develop a recurrence die from their disease,32 and even though the data are retrospective, long-term, follow-up studies suggest that recur-rence rates are lowered and that survival is improved in patients undergoing near-total or total thyroidectomy28,32-36 (Fig. 38-17). In addition, diminished survival is noted in patients with low-risk disease (mortality rates of 5% at 10 to 20 years), and it is not possible to accurately risk stratify patients preoperatively. In the last 10 years, a large study of >50,000 patients with papillary cancer demonstrated that, in multivariate analyses, total thyroid-ectomy led to a significantly improved recurrence and survival for tumors >1 cm. Furthermore, the authors also showed that |
Surgery_Schwartz_10864 | Surgery_Schwartz | papillary cancer demonstrated that, in multivariate analyses, total thyroid-ectomy led to a significantly improved recurrence and survival for tumors >1 cm. Furthermore, the authors also showed that patients with tumors 1 to 2 cm in diameter who were treated with lobectomy had a 24% higher risk of recurrence and a 49% higher risk of thyroid cancer mortality.37 Based on this informa-tion, the American Thyroid Association 2009 guidelines for the evidence-based management of thyroid cancers recommended a near-total or total thyroidectomy for primary cancers >1 cm unless there are contraindications to the surgery.38 However, additional studies since then have demonstrated no survival dif-ferences based on initial surgical procedure when adjusting for complexity/risk and comorbid diseases.39 This finding, coupled with a trend for increased use of ultrasound and Tg measure-ments to assess for recurrences and the declining use of RAI ablation, led to revised guidelines in 2015. Accordingly, | Surgery_Schwartz. papillary cancer demonstrated that, in multivariate analyses, total thyroid-ectomy led to a significantly improved recurrence and survival for tumors >1 cm. Furthermore, the authors also showed that patients with tumors 1 to 2 cm in diameter who were treated with lobectomy had a 24% higher risk of recurrence and a 49% higher risk of thyroid cancer mortality.37 Based on this informa-tion, the American Thyroid Association 2009 guidelines for the evidence-based management of thyroid cancers recommended a near-total or total thyroidectomy for primary cancers >1 cm unless there are contraindications to the surgery.38 However, additional studies since then have demonstrated no survival dif-ferences based on initial surgical procedure when adjusting for complexity/risk and comorbid diseases.39 This finding, coupled with a trend for increased use of ultrasound and Tg measure-ments to assess for recurrences and the declining use of RAI ablation, led to revised guidelines in 2015. Accordingly, |
Surgery_Schwartz_10865 | Surgery_Schwartz | finding, coupled with a trend for increased use of ultrasound and Tg measure-ments to assess for recurrences and the declining use of RAI ablation, led to revised guidelines in 2015. Accordingly, either near-total/total thyroidectomy or lobectomy constitute appropriate initial treatment for tumors >1 cm and <4 cm without extrathyroidal extension or lymph node involvement (cN0). Of note, the guidelines do state that the treatment team may elect near-total/total thyroidectomy to facilitate RAI ther-apy, enhance follow-up based on disease features, or if the patient expresses a preference for complete thyroid excision.40There has also been in change in the management of pap-illary microcarcinomas (<1 cm) since at least two trials from Japan have shown that active surveillance (defined as observa-tion without immediate surgery) can be a viable and safe first line of treatment for these very-low-risk tumors without extra-thyroidal extension or lymph node metastases.41 Tumors that progress | Surgery_Schwartz. finding, coupled with a trend for increased use of ultrasound and Tg measure-ments to assess for recurrences and the declining use of RAI ablation, led to revised guidelines in 2015. Accordingly, either near-total/total thyroidectomy or lobectomy constitute appropriate initial treatment for tumors >1 cm and <4 cm without extrathyroidal extension or lymph node involvement (cN0). Of note, the guidelines do state that the treatment team may elect near-total/total thyroidectomy to facilitate RAI ther-apy, enhance follow-up based on disease features, or if the patient expresses a preference for complete thyroid excision.40There has also been in change in the management of pap-illary microcarcinomas (<1 cm) since at least two trials from Japan have shown that active surveillance (defined as observa-tion without immediate surgery) can be a viable and safe first line of treatment for these very-low-risk tumors without extra-thyroidal extension or lymph node metastases.41 Tumors that progress |
Surgery_Schwartz_10866 | Surgery_Schwartz | without immediate surgery) can be a viable and safe first line of treatment for these very-low-risk tumors without extra-thyroidal extension or lymph node metastases.41 Tumors that progress during monitoring are treated by surgery. If surgery is chosen as initial treatment for these patients, a thyroid lobec-tomy is considered sufficient.When PTC is diagnosed by FNAB, the definitive operation can be done without confirming the diagnosis by frozen section during the operation. Patients with a nodule that is suspicious for papillary cancer should be treated by thyroid lobectomy, isthmu-sectomy, and removal of any pyramidal lobe or adjacent lymph nodes. If intraoperative frozen-section examination of a lymph node or primary tumor confirms carcinoma, completion total or near-total thyroidectomy is performed. If a definitive diagnosis cannot be made or the surgeon is concerned about the viability of the parathyroid glands or the status of the RLN, the opera-tion is terminated. When final | Surgery_Schwartz. without immediate surgery) can be a viable and safe first line of treatment for these very-low-risk tumors without extra-thyroidal extension or lymph node metastases.41 Tumors that progress during monitoring are treated by surgery. If surgery is chosen as initial treatment for these patients, a thyroid lobec-tomy is considered sufficient.When PTC is diagnosed by FNAB, the definitive operation can be done without confirming the diagnosis by frozen section during the operation. Patients with a nodule that is suspicious for papillary cancer should be treated by thyroid lobectomy, isthmu-sectomy, and removal of any pyramidal lobe or adjacent lymph nodes. If intraoperative frozen-section examination of a lymph node or primary tumor confirms carcinoma, completion total or near-total thyroidectomy is performed. If a definitive diagnosis cannot be made or the surgeon is concerned about the viability of the parathyroid glands or the status of the RLN, the opera-tion is terminated. When final |
Surgery_Schwartz_10867 | Surgery_Schwartz | is performed. If a definitive diagnosis cannot be made or the surgeon is concerned about the viability of the parathyroid glands or the status of the RLN, the opera-tion is terminated. When final histology confirms carcinoma, completion thyroidectomy is performed if deemed necessary based on risk-stratification. During thyroidectomy, enlarged or obviously involved central neck nodes should be removed (ther-apeutic central-compartment, level VI), along with nodes with known lateral neck metastases. Some investigators recommend routine bilateral central neck dissection due to the high inci-dence of microscopic metastases and data showing improved rates of recurrence and survival (compared to historic controls). 5Brunicardi_Ch38_p1625-p1704.indd 164801/03/19 11:21 AM 1649THYROID, PARATHYROID, AND ADRENALCHAPTER 38Table 38-6TNM classification of thyroid tumors PAPILLAEY or FOLLICULAR TUMORSDIAGNOSIS AGETUMORNODEMETASTASISSTAGE<55 yearsAny TAny NM0I<55 yearsAny TAny NM1II≥55 | Surgery_Schwartz. is performed. If a definitive diagnosis cannot be made or the surgeon is concerned about the viability of the parathyroid glands or the status of the RLN, the opera-tion is terminated. When final histology confirms carcinoma, completion thyroidectomy is performed if deemed necessary based on risk-stratification. During thyroidectomy, enlarged or obviously involved central neck nodes should be removed (ther-apeutic central-compartment, level VI), along with nodes with known lateral neck metastases. Some investigators recommend routine bilateral central neck dissection due to the high inci-dence of microscopic metastases and data showing improved rates of recurrence and survival (compared to historic controls). 5Brunicardi_Ch38_p1625-p1704.indd 164801/03/19 11:21 AM 1649THYROID, PARATHYROID, AND ADRENALCHAPTER 38Table 38-6TNM classification of thyroid tumors PAPILLAEY or FOLLICULAR TUMORSDIAGNOSIS AGETUMORNODEMETASTASISSTAGE<55 yearsAny TAny NM0I<55 yearsAny TAny NM1II≥55 |
Surgery_Schwartz_10868 | Surgery_Schwartz | PARATHYROID, AND ADRENALCHAPTER 38Table 38-6TNM classification of thyroid tumors PAPILLAEY or FOLLICULAR TUMORSDIAGNOSIS AGETUMORNODEMETASTASISSTAGE<55 yearsAny TAny NM0I<55 yearsAny TAny NM1II≥55 yearsT1N0/NXM0I≥55 yearsT1N1M0II≥55 yearsT2N0/NXM0I≥55 yearsT2N1M0II≥55 yearsT3a/T3bAny NM0II≥55 yearsT4aAny NM0III≥55 yearsT4bAny NM0IVA≥55 yearsAny TAny NM1IVBMEDULLARY THYROID CANCERTUMORNODEMETASTASISSTAGET1N0M0IT2N0M0IIT3N0M0IIT1–3N1aM0IIIT4aAny NM0IVAT1–3N1bM0IVAT4bAny NM0IVBAny TAny NM1IVCANAPLASTIC CANCERTUMORNODEMETASTASISSTAGET1–T3aN0/NXM0IVAT1–T3aN1M0IVBT3bAny NM0IVBT4Any NM0IVBAny TAny NM1IVCDEFINITIONSPrimary tumor (T)TX = Primary tumor cannot be assessedT0 = No evidence of primary tumorT1 = Tumor ≤2 cm in greatest dimension limited to the thyroid T1a = Tumor ≤1 cm in greatest dimension limited to the thyroid T1b = Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroidT2 = Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroidT3 = Tumor >4 cm limited to | Surgery_Schwartz. PARATHYROID, AND ADRENALCHAPTER 38Table 38-6TNM classification of thyroid tumors PAPILLAEY or FOLLICULAR TUMORSDIAGNOSIS AGETUMORNODEMETASTASISSTAGE<55 yearsAny TAny NM0I<55 yearsAny TAny NM1II≥55 yearsT1N0/NXM0I≥55 yearsT1N1M0II≥55 yearsT2N0/NXM0I≥55 yearsT2N1M0II≥55 yearsT3a/T3bAny NM0II≥55 yearsT4aAny NM0III≥55 yearsT4bAny NM0IVA≥55 yearsAny TAny NM1IVBMEDULLARY THYROID CANCERTUMORNODEMETASTASISSTAGET1N0M0IT2N0M0IIT3N0M0IIT1–3N1aM0IIIT4aAny NM0IVAT1–3N1bM0IVAT4bAny NM0IVBAny TAny NM1IVCANAPLASTIC CANCERTUMORNODEMETASTASISSTAGET1–T3aN0/NXM0IVAT1–T3aN1M0IVBT3bAny NM0IVBT4Any NM0IVBAny TAny NM1IVCDEFINITIONSPrimary tumor (T)TX = Primary tumor cannot be assessedT0 = No evidence of primary tumorT1 = Tumor ≤2 cm in greatest dimension limited to the thyroid T1a = Tumor ≤1 cm in greatest dimension limited to the thyroid T1b = Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroidT2 = Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroidT3 = Tumor >4 cm limited to |
Surgery_Schwartz_10869 | Surgery_Schwartz | limited to the thyroid T1b = Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroidT2 = Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroidT3 = Tumor >4 cm limited to the thyroid, or gross extrathyroidal extension invading only strap muscles T3a = Tumor >4 cm limited to the thyroid T3b = Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any sizeT4 = Includes gross extrathyroidal extension beyond the strap muscles T4a = Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size T4b = Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any sizeRegional lymph nodes (N)NX = Regional lymph nodes cannot be assessedN0 = No evidence of locoregional lymph node metastasis N0a = One or more cytologically or | Surgery_Schwartz. limited to the thyroid T1b = Tumor >1 cm but ≤2 cm in greatest dimension limited to the thyroidT2 = Tumor >2 cm but ≤4 cm in greatest dimension limited to the thyroidT3 = Tumor >4 cm limited to the thyroid, or gross extrathyroidal extension invading only strap muscles T3a = Tumor >4 cm limited to the thyroid T3b = Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any sizeT4 = Includes gross extrathyroidal extension beyond the strap muscles T4a = Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size T4b = Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any sizeRegional lymph nodes (N)NX = Regional lymph nodes cannot be assessedN0 = No evidence of locoregional lymph node metastasis N0a = One or more cytologically or |
Surgery_Schwartz_10870 | Surgery_Schwartz | vessels from a tumor of any sizeRegional lymph nodes (N)NX = Regional lymph nodes cannot be assessedN0 = No evidence of locoregional lymph node metastasis N0a = One or more cytologically or histologically confirmed benign lymph nodes N0b = No radiologic or clinical evidence of locoregional lymph node metastasisN1 = Metastasis to regional nodes N1a = Metastasis to level VI or VII (pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease. N1b = Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodesDistant Metastasis (M)M0 = No distant metastasisM1 = Distant metastasisUsed with the permission of the American College of Surgeons. Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.Brunicardi_Ch38_p1625-p1704.indd 164901/03/19 11:21 AM 1650SPECIFIC CONSIDERATIONSPART IIHowever, | Surgery_Schwartz. vessels from a tumor of any sizeRegional lymph nodes (N)NX = Regional lymph nodes cannot be assessedN0 = No evidence of locoregional lymph node metastasis N0a = One or more cytologically or histologically confirmed benign lymph nodes N0b = No radiologic or clinical evidence of locoregional lymph node metastasisN1 = Metastasis to regional nodes N1a = Metastasis to level VI or VII (pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease. N1b = Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodesDistant Metastasis (M)M0 = No distant metastasisM1 = Distant metastasisUsed with the permission of the American College of Surgeons. Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.Brunicardi_Ch38_p1625-p1704.indd 164901/03/19 11:21 AM 1650SPECIFIC CONSIDERATIONSPART IIHowever, |
Surgery_Schwartz_10871 | Surgery_Schwartz | MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.Brunicardi_Ch38_p1625-p1704.indd 164901/03/19 11:21 AM 1650SPECIFIC CONSIDERATIONSPART IIHowever, these risks need to be balanced with the increased risk of hypoparathyroidism with routine central neck dissection and the fact that some studies do not show any difference in recur-rence rates or rates of low or undetectable Tg levels. The updated 2015 ATA guidelines for thyroid cancer management suggest that prophylactic (ipsilateral or bilateral) dissection may be per-formed in patients with advanced (T3 or T4) papillary thyroid carcinoma, or if the lateral neck nodes are involved with tumor (N1b), or if the information will help in treatment planning.40 The American Head and Neck Society urges the involvement of multidisciplinary teams in the decision-making process for pro-phylactic CND and indicates that it can be considered in patients with high risk of recurrence (to include older | Surgery_Schwartz. MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.Brunicardi_Ch38_p1625-p1704.indd 164901/03/19 11:21 AM 1650SPECIFIC CONSIDERATIONSPART IIHowever, these risks need to be balanced with the increased risk of hypoparathyroidism with routine central neck dissection and the fact that some studies do not show any difference in recur-rence rates or rates of low or undetectable Tg levels. The updated 2015 ATA guidelines for thyroid cancer management suggest that prophylactic (ipsilateral or bilateral) dissection may be per-formed in patients with advanced (T3 or T4) papillary thyroid carcinoma, or if the lateral neck nodes are involved with tumor (N1b), or if the information will help in treatment planning.40 The American Head and Neck Society urges the involvement of multidisciplinary teams in the decision-making process for pro-phylactic CND and indicates that it can be considered in patients with high risk of recurrence (to include older |
Surgery_Schwartz_10872 | Surgery_Schwartz | the involvement of multidisciplinary teams in the decision-making process for pro-phylactic CND and indicates that it can be considered in patients with high risk of recurrence (to include older or young age, mul-tifocal disease and extrathyroidal extension in addition to the aforementioned factors).42 Further prospective studies are needed before definitive recommendations can be made in this regard.Biopsy-proven lymph node metastases detected clini-cally or by imaging in the lateral neck in patients with papil-lary carcinoma are managed with modified radical or functional neck dissection,40 as described later in this chapter in “Thyroid Surgery.” Dissection of the posterior triangle and suprahyoid dissection usually are not necessary unless there is extensive metastatic disease in levels 2, 3, and 4, but should be performed when appropriate. Prophylactic lateral neck node dissection is not necessary in patients with PTC because these cancers do not appear to metastasize systemically | Surgery_Schwartz. the involvement of multidisciplinary teams in the decision-making process for pro-phylactic CND and indicates that it can be considered in patients with high risk of recurrence (to include older or young age, mul-tifocal disease and extrathyroidal extension in addition to the aforementioned factors).42 Further prospective studies are needed before definitive recommendations can be made in this regard.Biopsy-proven lymph node metastases detected clini-cally or by imaging in the lateral neck in patients with papil-lary carcinoma are managed with modified radical or functional neck dissection,40 as described later in this chapter in “Thyroid Surgery.” Dissection of the posterior triangle and suprahyoid dissection usually are not necessary unless there is extensive metastatic disease in levels 2, 3, and 4, but should be performed when appropriate. Prophylactic lateral neck node dissection is not necessary in patients with PTC because these cancers do not appear to metastasize systemically |
Surgery_Schwartz_10873 | Surgery_Schwartz | 2, 3, and 4, but should be performed when appropriate. Prophylactic lateral neck node dissection is not necessary in patients with PTC because these cancers do not appear to metastasize systemically from lymph nodes, and micrometastases often can be ablated with RAI therapy.Follicular Carcinoma Follicular carcinomas account for 10% of thyroid cancers and occur more commonly in iodinedeficient areas. The overall incidence of this tumor is declining in the United States, probably due to iodine supplementation and improved histologic classification. Women have a higher incidence of follicular cancer, with a female-to-male ratio of 3:1, and a mean age at presentation of 50 years old. Follicular cancers usually present as solitary thyroid nodules, occasion-ally with a history of rapid size increase, and long-standing goi-ter. Pain is uncommon, unless hemorrhage into the nodule has occurred. Unlike papillary cancers, cervical lymphadenopathy is uncommon at initial presentation (about 5%), | Surgery_Schwartz. 2, 3, and 4, but should be performed when appropriate. Prophylactic lateral neck node dissection is not necessary in patients with PTC because these cancers do not appear to metastasize systemically from lymph nodes, and micrometastases often can be ablated with RAI therapy.Follicular Carcinoma Follicular carcinomas account for 10% of thyroid cancers and occur more commonly in iodinedeficient areas. The overall incidence of this tumor is declining in the United States, probably due to iodine supplementation and improved histologic classification. Women have a higher incidence of follicular cancer, with a female-to-male ratio of 3:1, and a mean age at presentation of 50 years old. Follicular cancers usually present as solitary thyroid nodules, occasion-ally with a history of rapid size increase, and long-standing goi-ter. Pain is uncommon, unless hemorrhage into the nodule has occurred. Unlike papillary cancers, cervical lymphadenopathy is uncommon at initial presentation (about 5%), |
Surgery_Schwartz_10874 | Surgery_Schwartz | and long-standing goi-ter. Pain is uncommon, unless hemorrhage into the nodule has occurred. Unlike papillary cancers, cervical lymphadenopathy is uncommon at initial presentation (about 5%), although distant metastases may be present. In <1% of cases, follicular cancers may be hyperfunctioning, leading patients to present with signs and symptoms of thyrotoxicosis. FNAB is unable to distinguish benign follicular lesions from follicular carcinomas. Therefore, preoperative clinical diagnosis of cancer is difficult unless dis-tant metastases are present. Large follicular tumors (>4 cm) in older men are more likely to be malignant.Due to the limitations inherent in the FNAB diagnosis, a number of studies have focused on identifying molecular mark-ers to distinguish benign from malignant follicular lesions. Many of these genetic changes can be identified using tissue obtained during FNAB. While no single marker has met the ideal charac-teristics of being simple to use, reproducible, and | Surgery_Schwartz. and long-standing goi-ter. Pain is uncommon, unless hemorrhage into the nodule has occurred. Unlike papillary cancers, cervical lymphadenopathy is uncommon at initial presentation (about 5%), although distant metastases may be present. In <1% of cases, follicular cancers may be hyperfunctioning, leading patients to present with signs and symptoms of thyrotoxicosis. FNAB is unable to distinguish benign follicular lesions from follicular carcinomas. Therefore, preoperative clinical diagnosis of cancer is difficult unless dis-tant metastases are present. Large follicular tumors (>4 cm) in older men are more likely to be malignant.Due to the limitations inherent in the FNAB diagnosis, a number of studies have focused on identifying molecular mark-ers to distinguish benign from malignant follicular lesions. Many of these genetic changes can be identified using tissue obtained during FNAB. While no single marker has met the ideal charac-teristics of being simple to use, reproducible, and |
Surgery_Schwartz_10875 | Surgery_Schwartz | lesions. Many of these genetic changes can be identified using tissue obtained during FNAB. While no single marker has met the ideal charac-teristics of being simple to use, reproducible, and cost-effective, several combinations of markers appear to be useful in differen-tiating benign from malignant lesions. A commonly used panel of seven genes used to “rule in” malignancy detects mutations in BRAF, Ras, RET/PTC, and PAX/PPARg and has been associated with a sensitivity of 57% to 75%, specificity of 97% to 100%, PPV of 87% to 100%, and NPV of 79% to 86% in the case of nodules consistent with Follicular/Hürthle cell neoplasm or sus-picious of the same.43 In contrast, the Afirma Gene Expression Classifier (GEC) uses a “rule out” strategy to identify benign nodules. This method uses material from additional FNA passes (in an RNA-preserving solution) to analyze a 167 gene panel, and the results obtained are reported as benign or suspicious.44 It is reported to have a lower PPV of 37% but | Surgery_Schwartz. lesions. Many of these genetic changes can be identified using tissue obtained during FNAB. While no single marker has met the ideal charac-teristics of being simple to use, reproducible, and cost-effective, several combinations of markers appear to be useful in differen-tiating benign from malignant lesions. A commonly used panel of seven genes used to “rule in” malignancy detects mutations in BRAF, Ras, RET/PTC, and PAX/PPARg and has been associated with a sensitivity of 57% to 75%, specificity of 97% to 100%, PPV of 87% to 100%, and NPV of 79% to 86% in the case of nodules consistent with Follicular/Hürthle cell neoplasm or sus-picious of the same.43 In contrast, the Afirma Gene Expression Classifier (GEC) uses a “rule out” strategy to identify benign nodules. This method uses material from additional FNA passes (in an RNA-preserving solution) to analyze a 167 gene panel, and the results obtained are reported as benign or suspicious.44 It is reported to have a lower PPV of 37% but |
Surgery_Schwartz_10876 | Surgery_Schwartz | from additional FNA passes (in an RNA-preserving solution) to analyze a 167 gene panel, and the results obtained are reported as benign or suspicious.44 It is reported to have a lower PPV of 37% but a better NPV of 94% for Follicular/Hürthle cell neoplasms. Next generation sequenc-ing techniques have been used to enhance malignancy detection Less than near-totalthyroidectomyP = 0.02Less thannear-totalthyroidectomy00510152025303524681012Cumulative death (%)Near-total or totalthyroidectomyNear-totalor totalthyroidectomyYears after initial therapy04361135262907227218111200640290698555464416365131432092100032Figure 38-17. Improved survival in patients with papillary or follicular thyroid cancer following total or near-total thyroidectomy compared to those who underwent less than near-total thyroidectomy. (Reproduced with permission from Mazzaferri E, Jhiang S: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer, Am J Med. 1994 | Surgery_Schwartz. from additional FNA passes (in an RNA-preserving solution) to analyze a 167 gene panel, and the results obtained are reported as benign or suspicious.44 It is reported to have a lower PPV of 37% but a better NPV of 94% for Follicular/Hürthle cell neoplasms. Next generation sequenc-ing techniques have been used to enhance malignancy detection Less than near-totalthyroidectomyP = 0.02Less thannear-totalthyroidectomy00510152025303524681012Cumulative death (%)Near-total or totalthyroidectomyNear-totalor totalthyroidectomyYears after initial therapy04361135262907227218111200640290698555464416365131432092100032Figure 38-17. Improved survival in patients with papillary or follicular thyroid cancer following total or near-total thyroidectomy compared to those who underwent less than near-total thyroidectomy. (Reproduced with permission from Mazzaferri E, Jhiang S: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer, Am J Med. 1994 |
Surgery_Schwartz_10877 | Surgery_Schwartz | near-total thyroidectomy. (Reproduced with permission from Mazzaferri E, Jhiang S: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer, Am J Med. 1994 Nov;97(5):418-428.)Brunicardi_Ch38_p1625-p1704.indd 165001/03/19 11:21 AM 1651THYROID, PARATHYROID, AND ADRENALCHAPTER 38by including additional mutations and gene arrangements. The advanced version of this assay (ThyroSeqV2) had a sensitivity of 90%, specificity of 93%, PPV of 83%, and NPV of 96% in a study of Follicular/Hüurthle cell neoplasm/suspicious of the same nodules, making it useful as both a “rule in” and “rule out” test.45 Of note, these assays have also been evaluated in “AUS/FLUS” and “suspicious for malignancy” nodules with varying results, i.e., the performance characteristics of these tests have been noted to change depending upon the prevalence of malig-nancy in the tested population (pretest probability). At this time, the ATA guidelines do not advise molecular | Surgery_Schwartz. near-total thyroidectomy. (Reproduced with permission from Mazzaferri E, Jhiang S: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer, Am J Med. 1994 Nov;97(5):418-428.)Brunicardi_Ch38_p1625-p1704.indd 165001/03/19 11:21 AM 1651THYROID, PARATHYROID, AND ADRENALCHAPTER 38by including additional mutations and gene arrangements. The advanced version of this assay (ThyroSeqV2) had a sensitivity of 90%, specificity of 93%, PPV of 83%, and NPV of 96% in a study of Follicular/Hüurthle cell neoplasm/suspicious of the same nodules, making it useful as both a “rule in” and “rule out” test.45 Of note, these assays have also been evaluated in “AUS/FLUS” and “suspicious for malignancy” nodules with varying results, i.e., the performance characteristics of these tests have been noted to change depending upon the prevalence of malig-nancy in the tested population (pretest probability). At this time, the ATA guidelines do not advise molecular |
Surgery_Schwartz_10878 | Surgery_Schwartz | of these tests have been noted to change depending upon the prevalence of malig-nancy in the tested population (pretest probability). At this time, the ATA guidelines do not advise molecular testing in the work-up of “suspicious for malignancy” nodules. Molecular testing may be used to supplement cytology results for malignancy risk assessment in “AUS/FLUS” or “follicular/Hürthle cell neo-plasm/suspicious of the same” nodules depending on feasibility and informed patient preference.40 Expression arrays also have been used to investigate the role of microRNAs, which are a new class of small, noncoding RNAs that have been implicated in carcinogenesis. The specific microRNAs miR-197 and miR-346 are upregulated in follicular thyroid cancers46 and have the potential to be used as diagnostic markers. Additional studies have also demonstrated the feasibility of studying a panel of microRNAs in a small number of FNA samples. ThyGenX/ThyraMIR uses a mutation panel supplemented with 10 miRNA | Surgery_Schwartz. of these tests have been noted to change depending upon the prevalence of malig-nancy in the tested population (pretest probability). At this time, the ATA guidelines do not advise molecular testing in the work-up of “suspicious for malignancy” nodules. Molecular testing may be used to supplement cytology results for malignancy risk assessment in “AUS/FLUS” or “follicular/Hürthle cell neo-plasm/suspicious of the same” nodules depending on feasibility and informed patient preference.40 Expression arrays also have been used to investigate the role of microRNAs, which are a new class of small, noncoding RNAs that have been implicated in carcinogenesis. The specific microRNAs miR-197 and miR-346 are upregulated in follicular thyroid cancers46 and have the potential to be used as diagnostic markers. Additional studies have also demonstrated the feasibility of studying a panel of microRNAs in a small number of FNA samples. ThyGenX/ThyraMIR uses a mutation panel supplemented with 10 miRNA |
Surgery_Schwartz_10879 | Surgery_Schwartz | markers. Additional studies have also demonstrated the feasibility of studying a panel of microRNAs in a small number of FNA samples. ThyGenX/ThyraMIR uses a mutation panel supplemented with 10 miRNA markers,47 whereas Rosetta GX Reveal is exclusively based on miRNA markers; however, both require further validation.48Pathology. Follicular carcinomas usually are solitary lesions, and the majority are surrounded by a capsule. Histologically, follicles are present, but the lumen may be devoid of colloid. Architectural patterns depend on the degree of differentiation demonstrated by the tumor. Malignancy is defined by the pres-ence of capsular and vascular invasion (Fig. 38-18). In general, minimally invasive tumors appear grossly encapsulated and have microscopic invasion through the tumor capsule without extension into the parenchyma and/or invasion into smallto medium-sized vessels (venous caliber) in or immediately out-side the capsule, but not within the tumor. On the other hand, | Surgery_Schwartz. markers. Additional studies have also demonstrated the feasibility of studying a panel of microRNAs in a small number of FNA samples. ThyGenX/ThyraMIR uses a mutation panel supplemented with 10 miRNA markers,47 whereas Rosetta GX Reveal is exclusively based on miRNA markers; however, both require further validation.48Pathology. Follicular carcinomas usually are solitary lesions, and the majority are surrounded by a capsule. Histologically, follicles are present, but the lumen may be devoid of colloid. Architectural patterns depend on the degree of differentiation demonstrated by the tumor. Malignancy is defined by the pres-ence of capsular and vascular invasion (Fig. 38-18). In general, minimally invasive tumors appear grossly encapsulated and have microscopic invasion through the tumor capsule without extension into the parenchyma and/or invasion into smallto medium-sized vessels (venous caliber) in or immediately out-side the capsule, but not within the tumor. On the other hand, |
Surgery_Schwartz_10880 | Surgery_Schwartz | capsule without extension into the parenchyma and/or invasion into smallto medium-sized vessels (venous caliber) in or immediately out-side the capsule, but not within the tumor. On the other hand, widely invasive tumors demonstrate evidence of large vessel invasion and/or broad areas of tumor invasion through the cap-sule. They may, in fact, be unencapsulated. It is important to note that there is a wide variation of opinion among clinicians and pathologists with respect to the above definitions. Tumor infiltration and invasion, as well as tumor thrombus within the middle thyroid or jugular veins, may be apparent at operation.Surgical Treatment and Prognosis. Patients diagnosed by FNAB as having a follicular lesion should undergo thyroid lobectomy because at least 70% to 80% of these patients will have benign adenomas. Total thyroidectomy is recommended by some surgeons in older patients with follicular lesions >4 cm because of the higher risk of cancer in this setting (50%) and | Surgery_Schwartz. capsule without extension into the parenchyma and/or invasion into smallto medium-sized vessels (venous caliber) in or immediately out-side the capsule, but not within the tumor. On the other hand, widely invasive tumors demonstrate evidence of large vessel invasion and/or broad areas of tumor invasion through the cap-sule. They may, in fact, be unencapsulated. It is important to note that there is a wide variation of opinion among clinicians and pathologists with respect to the above definitions. Tumor infiltration and invasion, as well as tumor thrombus within the middle thyroid or jugular veins, may be apparent at operation.Surgical Treatment and Prognosis. Patients diagnosed by FNAB as having a follicular lesion should undergo thyroid lobectomy because at least 70% to 80% of these patients will have benign adenomas. Total thyroidectomy is recommended by some surgeons in older patients with follicular lesions >4 cm because of the higher risk of cancer in this setting (50%) and |
Surgery_Schwartz_10881 | Surgery_Schwartz | patients will have benign adenomas. Total thyroidectomy is recommended by some surgeons in older patients with follicular lesions >4 cm because of the higher risk of cancer in this setting (50%) and certainly should be performed in patients with atypia on FNA, a family history of thyroid cancer, or a history of radiation exposure. Intraoperative frozen-section examination usually is not helpful, but it should be performed when there is evidence of capsular or vascular invasion or when adjacent lymphadenopa-thy is present. Total thyroidectomy should be performed when thyroid cancer is diagnosed. There is debate among experts about whether patients with minimally invasive follicular can-cers should undergo completion thyroidectomy because the prognosis is so good in these patients. A diagnosis of frankly invasive carcinoma or follicular carcinoma with angioinvasion, with or without capsular invasion, necessitates completion of total thyroidectomy primarily so that 131I can be used to | Surgery_Schwartz. patients will have benign adenomas. Total thyroidectomy is recommended by some surgeons in older patients with follicular lesions >4 cm because of the higher risk of cancer in this setting (50%) and certainly should be performed in patients with atypia on FNA, a family history of thyroid cancer, or a history of radiation exposure. Intraoperative frozen-section examination usually is not helpful, but it should be performed when there is evidence of capsular or vascular invasion or when adjacent lymphadenopa-thy is present. Total thyroidectomy should be performed when thyroid cancer is diagnosed. There is debate among experts about whether patients with minimally invasive follicular can-cers should undergo completion thyroidectomy because the prognosis is so good in these patients. A diagnosis of frankly invasive carcinoma or follicular carcinoma with angioinvasion, with or without capsular invasion, necessitates completion of total thyroidectomy primarily so that 131I can be used to |
Surgery_Schwartz_10882 | Surgery_Schwartz | of frankly invasive carcinoma or follicular carcinoma with angioinvasion, with or without capsular invasion, necessitates completion of total thyroidectomy primarily so that 131I can be used to detect and ablate metastatic disease. Prophylactic nodal dissection is not needed because nodal involvement is infrequent, but in the unusual patient with nodal metastases, therapeutic neck dissec-tion is recommended. Prophylactic central neck dissection may be considered in patients with large tumors. The cumulative mortality from follicular thyroid cancer is approximately 15% at 10 years and 30% at 20 years. Poor long-term prognosis is predicted by age over 50 years old at presentation, tumor size >4 cm, higher tumor grade, marked vascular invasion, extrathy-roidal invasion, and distant metastases at the time of diagnosis.Hürthle Cell Carcinoma Hürthle cell carcinomas account for approximately 3% of all thyroid malignancies and, under the World Health Organization classification, are | Surgery_Schwartz. of frankly invasive carcinoma or follicular carcinoma with angioinvasion, with or without capsular invasion, necessitates completion of total thyroidectomy primarily so that 131I can be used to detect and ablate metastatic disease. Prophylactic nodal dissection is not needed because nodal involvement is infrequent, but in the unusual patient with nodal metastases, therapeutic neck dissec-tion is recommended. Prophylactic central neck dissection may be considered in patients with large tumors. The cumulative mortality from follicular thyroid cancer is approximately 15% at 10 years and 30% at 20 years. Poor long-term prognosis is predicted by age over 50 years old at presentation, tumor size >4 cm, higher tumor grade, marked vascular invasion, extrathy-roidal invasion, and distant metastases at the time of diagnosis.Hürthle Cell Carcinoma Hürthle cell carcinomas account for approximately 3% of all thyroid malignancies and, under the World Health Organization classification, are |
Surgery_Schwartz_10883 | Surgery_Schwartz | at the time of diagnosis.Hürthle Cell Carcinoma Hürthle cell carcinomas account for approximately 3% of all thyroid malignancies and, under the World Health Organization classification, are considered to be a subtype of follicular thyroid cancer. Hürthle cell cancers also are characterized by vascular or capsular invasion and, there-fore, cannot be diagnosed by FNAB. Tumors contain sheets of eosinophilic cells packed with mitochondria, which are derived from the oxyphilic cells of the thyroid gland. Hürthle cell tumors differ from follicular carcinomas in that they are more often multifocal and bilateral (about 30%), usually do not take up RAI (about 5%), are more likely to metastasize to local nodes (25%) and distant sites, and are associated with a higher mortal-ity rate (about 20% at 10 years). Hence, they are considered to be a separate class of tumors by some groups.Management is similar to that of follicular neoplasms, with lobectomy and isthmusectomy being sufficient surgical | Surgery_Schwartz. at the time of diagnosis.Hürthle Cell Carcinoma Hürthle cell carcinomas account for approximately 3% of all thyroid malignancies and, under the World Health Organization classification, are considered to be a subtype of follicular thyroid cancer. Hürthle cell cancers also are characterized by vascular or capsular invasion and, there-fore, cannot be diagnosed by FNAB. Tumors contain sheets of eosinophilic cells packed with mitochondria, which are derived from the oxyphilic cells of the thyroid gland. Hürthle cell tumors differ from follicular carcinomas in that they are more often multifocal and bilateral (about 30%), usually do not take up RAI (about 5%), are more likely to metastasize to local nodes (25%) and distant sites, and are associated with a higher mortal-ity rate (about 20% at 10 years). Hence, they are considered to be a separate class of tumors by some groups.Management is similar to that of follicular neoplasms, with lobectomy and isthmusectomy being sufficient surgical |
Surgery_Schwartz_10884 | Surgery_Schwartz | 10 years). Hence, they are considered to be a separate class of tumors by some groups.Management is similar to that of follicular neoplasms, with lobectomy and isthmusectomy being sufficient surgical treatment for unilateral Hürthle cell adenomas. When Hürthle cell neoplasms are found to be invasive on definitive paraffin-section histology, then total thyroidectomy should be performed. These patients should also undergo routine central neck node removal, similar to patients with MTC, and modified radical neck dissection when lateral neck nodes are palpable or identi-fied by ultrasonography. Although RAI scanning and ablation usually are ineffective, they probably should be considered to ablate any residual normal thyroid tissue and occasionally ablate tumors because there is no other good therapy.Postoperative Management of Differentiated Thyroid Cancer Radioiodine Therapy The issue of whether RAI therapy offers any benefit to patients with differentiated thyroid cancer Figure | Surgery_Schwartz. 10 years). Hence, they are considered to be a separate class of tumors by some groups.Management is similar to that of follicular neoplasms, with lobectomy and isthmusectomy being sufficient surgical treatment for unilateral Hürthle cell adenomas. When Hürthle cell neoplasms are found to be invasive on definitive paraffin-section histology, then total thyroidectomy should be performed. These patients should also undergo routine central neck node removal, similar to patients with MTC, and modified radical neck dissection when lateral neck nodes are palpable or identi-fied by ultrasonography. Although RAI scanning and ablation usually are ineffective, they probably should be considered to ablate any residual normal thyroid tissue and occasionally ablate tumors because there is no other good therapy.Postoperative Management of Differentiated Thyroid Cancer Radioiodine Therapy The issue of whether RAI therapy offers any benefit to patients with differentiated thyroid cancer Figure |
Surgery_Schwartz_10885 | Surgery_Schwartz | good therapy.Postoperative Management of Differentiated Thyroid Cancer Radioiodine Therapy The issue of whether RAI therapy offers any benefit to patients with differentiated thyroid cancer Figure 38-18. Hematoxylin-eosin–stained section from follicular thyroid carcinoma showing capsular invasion.Brunicardi_Ch38_p1625-p1704.indd 165101/03/19 11:21 AM 1652SPECIFIC CONSIDERATIONSPART IIremains controversial in the absence of prospective, random-ized controlled trials. Long-term cohort studies by Mazzaferri and associates and DeGroot and colleagues demonstrate that postoperative RAI therapy reduces recurrence (Fig. 38-19) and provides a small improvement in survival, even in low-risk patients.28,34 Screening with RAI is more sensitive than chest X-ray or CT scanning for detecting metastases; however, it is less sensitive than Tg measurements for detecting metastatic disease in most differentiated thyroid cancers except Hürthle cell tumors. Screening and treatment are facilitated by | Surgery_Schwartz. good therapy.Postoperative Management of Differentiated Thyroid Cancer Radioiodine Therapy The issue of whether RAI therapy offers any benefit to patients with differentiated thyroid cancer Figure 38-18. Hematoxylin-eosin–stained section from follicular thyroid carcinoma showing capsular invasion.Brunicardi_Ch38_p1625-p1704.indd 165101/03/19 11:21 AM 1652SPECIFIC CONSIDERATIONSPART IIremains controversial in the absence of prospective, random-ized controlled trials. Long-term cohort studies by Mazzaferri and associates and DeGroot and colleagues demonstrate that postoperative RAI therapy reduces recurrence (Fig. 38-19) and provides a small improvement in survival, even in low-risk patients.28,34 Screening with RAI is more sensitive than chest X-ray or CT scanning for detecting metastases; however, it is less sensitive than Tg measurements for detecting metastatic disease in most differentiated thyroid cancers except Hürthle cell tumors. Screening and treatment are facilitated by |
Surgery_Schwartz_10886 | Surgery_Schwartz | however, it is less sensitive than Tg measurements for detecting metastatic disease in most differentiated thyroid cancers except Hürthle cell tumors. Screening and treatment are facilitated by the removal of all normal thyroid tissue, which effectively competes for iodine uptake. Metastatic differentiated thyroid carcinoma can be detected and treated by 131I in about 75% of patients. Multiple studies show that RAI effectively treats >70% of lung micrometastases that are detected by RAI scan in the presence of a normal chest X-ray, whereas the success rates drop to <10% with pulmonary macrometastases. Early detection therefore is very important to improve prognosis.Several features place patients at increased risk for local recurrences or metastases. The 2015 ATA guidelines use various features to risk-stratify tumors.40 Low-risk papillary thyroid cancer includes those without local tumor invasion, all macroscopic tumor resected, absence of aggressive histol-ogy (e.g., tall cell, | Surgery_Schwartz. however, it is less sensitive than Tg measurements for detecting metastatic disease in most differentiated thyroid cancers except Hürthle cell tumors. Screening and treatment are facilitated by the removal of all normal thyroid tissue, which effectively competes for iodine uptake. Metastatic differentiated thyroid carcinoma can be detected and treated by 131I in about 75% of patients. Multiple studies show that RAI effectively treats >70% of lung micrometastases that are detected by RAI scan in the presence of a normal chest X-ray, whereas the success rates drop to <10% with pulmonary macrometastases. Early detection therefore is very important to improve prognosis.Several features place patients at increased risk for local recurrences or metastases. The 2015 ATA guidelines use various features to risk-stratify tumors.40 Low-risk papillary thyroid cancer includes those without local tumor invasion, all macroscopic tumor resected, absence of aggressive histol-ogy (e.g., tall cell, |
Surgery_Schwartz_10887 | Surgery_Schwartz | features to risk-stratify tumors.40 Low-risk papillary thyroid cancer includes those without local tumor invasion, all macroscopic tumor resected, absence of aggressive histol-ogy (e.g., tall cell, columnar cell carcinoma), no known dis-tant metastases (clinical or on RAI scan if done), no vascular invasion, clinical N0 or ≤5 pathologic N1 micrometastases (<0.2 cm in largest dimension), intrathyroidal, encapsulated fol-licular variant of papillary thyroid cancer, intrathyroidal, well differentiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion and intrathyroi-dal papillary microcarcinoma (unifocal or multifocal, including BRAFV600E mutated). Intermediate-risk tumors include those showing microscopic invasion of tumor into the perithyroidal soft tissues or RAI-avid metastatic foci in the neck on the first posttreatment whole-body RAI scan. This group also includes tumors with aggressive histology (e.g., tall cell, columnar cell | Surgery_Schwartz. features to risk-stratify tumors.40 Low-risk papillary thyroid cancer includes those without local tumor invasion, all macroscopic tumor resected, absence of aggressive histol-ogy (e.g., tall cell, columnar cell carcinoma), no known dis-tant metastases (clinical or on RAI scan if done), no vascular invasion, clinical N0 or ≤5 pathologic N1 micrometastases (<0.2 cm in largest dimension), intrathyroidal, encapsulated fol-licular variant of papillary thyroid cancer, intrathyroidal, well differentiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion and intrathyroi-dal papillary microcarcinoma (unifocal or multifocal, including BRAFV600E mutated). Intermediate-risk tumors include those showing microscopic invasion of tumor into the perithyroidal soft tissues or RAI-avid metastatic foci in the neck on the first posttreatment whole-body RAI scan. This group also includes tumors with aggressive histology (e.g., tall cell, columnar cell |
Surgery_Schwartz_10888 | Surgery_Schwartz | soft tissues or RAI-avid metastatic foci in the neck on the first posttreatment whole-body RAI scan. This group also includes tumors with aggressive histology (e.g., tall cell, columnar cell carcinoma), papillary thyroid cancer with vascular invasion, clinical N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest dimension and multifocal papillary microcar-cinoma with extra-thyroidal extension (ETE) and BRAFV600E mutated (if known). High-risk tumors include those demon-strating macroscopic invasion of tumor into the perithyroidal soft tissues (gross ETE), incomplete tumor resection, and pres-ence of distant metastases (or postoperative serum thyroglobu-lin suggestive of distant metastase) or pathologic N1 with any metastatic lymph node ≥3 cm in largest dimension. Follicular thyroid cancers with extensive vascular invasion (>4 foci of vascular invasion) also fall into this category. It is important to note that this risk assessment represents a continuum with recurrence | Surgery_Schwartz. soft tissues or RAI-avid metastatic foci in the neck on the first posttreatment whole-body RAI scan. This group also includes tumors with aggressive histology (e.g., tall cell, columnar cell carcinoma), papillary thyroid cancer with vascular invasion, clinical N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest dimension and multifocal papillary microcar-cinoma with extra-thyroidal extension (ETE) and BRAFV600E mutated (if known). High-risk tumors include those demon-strating macroscopic invasion of tumor into the perithyroidal soft tissues (gross ETE), incomplete tumor resection, and pres-ence of distant metastases (or postoperative serum thyroglobu-lin suggestive of distant metastase) or pathologic N1 with any metastatic lymph node ≥3 cm in largest dimension. Follicular thyroid cancers with extensive vascular invasion (>4 foci of vascular invasion) also fall into this category. It is important to note that this risk assessment represents a continuum with recurrence |
Surgery_Schwartz_10889 | Surgery_Schwartz | thyroid cancers with extensive vascular invasion (>4 foci of vascular invasion) also fall into this category. It is important to note that this risk assessment represents a continuum with recurrence rates from 1% to 2% for low-risk cancers to >50% for high-risk cancers.The current ATA guidelines recommend RAI therapy after surgical treatment for all patients with high-risk disease, i.e., those with gross ETE and M1 disease. RAI therapy is not rec-ommended for patients with papillary microcarcinomas, either uni -or multifocal. RAI remnant ablation is not routinely recom-mended after thyroidectomy for ATA low-risk DTC patients. However, it may be considered in patients with aggressive histology or vascular invasion. Consideration of RAI is recom-mended for patients with intermediate-risk disease and “gen-erally favored” for patients with microscopic ETE due to the risk of recurrent disease, large (>2–3 cm) or clinically evident lymph nodes (central, mediastinal, and lateral neck) or | Surgery_Schwartz. thyroid cancers with extensive vascular invasion (>4 foci of vascular invasion) also fall into this category. It is important to note that this risk assessment represents a continuum with recurrence rates from 1% to 2% for low-risk cancers to >50% for high-risk cancers.The current ATA guidelines recommend RAI therapy after surgical treatment for all patients with high-risk disease, i.e., those with gross ETE and M1 disease. RAI therapy is not rec-ommended for patients with papillary microcarcinomas, either uni -or multifocal. RAI remnant ablation is not routinely recom-mended after thyroidectomy for ATA low-risk DTC patients. However, it may be considered in patients with aggressive histology or vascular invasion. Consideration of RAI is recom-mended for patients with intermediate-risk disease and “gen-erally favored” for patients with microscopic ETE due to the risk of recurrent disease, large (>2–3 cm) or clinically evident lymph nodes (central, mediastinal, and lateral neck) or |
Surgery_Schwartz_10890 | Surgery_Schwartz | disease and “gen-erally favored” for patients with microscopic ETE due to the risk of recurrent disease, large (>2–3 cm) or clinically evident lymph nodes (central, mediastinal, and lateral neck) or presence of extranodal extension. Advancing age may also favor RAI use. However, RAI is not needed for patients with a few (<5) microscopic nodal metastases in the central compartment in the absence of other adverse features as there is insufficient evi-dence for its utility in this setting. It is generally favored for patients with lateral neck disease. There is currently no estab-lished role for molecular testing in determining RAI therapy.Remnant ablation can be performed with either thyroid hormone withdrawal or recombinant TSH (rTSH) stimula-tion. This is based on randomized studies showing that both techniques are equally effective in preparing patients for abla-tion, with the latter being associated with an improved quality of life.49,50 In patients with ATA high-risk disease | Surgery_Schwartz. disease and “gen-erally favored” for patients with microscopic ETE due to the risk of recurrent disease, large (>2–3 cm) or clinically evident lymph nodes (central, mediastinal, and lateral neck) or presence of extranodal extension. Advancing age may also favor RAI use. However, RAI is not needed for patients with a few (<5) microscopic nodal metastases in the central compartment in the absence of other adverse features as there is insufficient evi-dence for its utility in this setting. It is generally favored for patients with lateral neck disease. There is currently no estab-lished role for molecular testing in determining RAI therapy.Remnant ablation can be performed with either thyroid hormone withdrawal or recombinant TSH (rTSH) stimula-tion. This is based on randomized studies showing that both techniques are equally effective in preparing patients for abla-tion, with the latter being associated with an improved quality of life.49,50 In patients with ATA high-risk disease |
Surgery_Schwartz_10891 | Surgery_Schwartz | showing that both techniques are equally effective in preparing patients for abla-tion, with the latter being associated with an improved quality of life.49,50 In patients with ATA high-risk disease (including distant metastases), there is insufficient data to recommend thy-rogen-mediated ablation, and hormone withdrawal is preferred. Furthermore, if patients have comorbidities that can be exac-erbated by severe hypothyroidism (cardiac or psychiatric con-ditions), consideration should be given to thyrogen-mediated RAI. If hormone withdrawal is used, T4 therapy should be dis-continued for approximately 6 weeks before scanning with 131I. Patients should receive T3 during this time period to decrease the period of hypothyroidism. T3 has a shorter half-life than T4 (1 day vs. 1 week) and needs to be discontinued for 2 weeks to allow TSH levels to rise before treatment. Levels >30 mU/L are considered optimal, based on noncontrolled studies. A low-iodine diet also is recommended during this | Surgery_Schwartz. showing that both techniques are equally effective in preparing patients for abla-tion, with the latter being associated with an improved quality of life.49,50 In patients with ATA high-risk disease (including distant metastases), there is insufficient data to recommend thy-rogen-mediated ablation, and hormone withdrawal is preferred. Furthermore, if patients have comorbidities that can be exac-erbated by severe hypothyroidism (cardiac or psychiatric con-ditions), consideration should be given to thyrogen-mediated RAI. If hormone withdrawal is used, T4 therapy should be dis-continued for approximately 6 weeks before scanning with 131I. Patients should receive T3 during this time period to decrease the period of hypothyroidism. T3 has a shorter half-life than T4 (1 day vs. 1 week) and needs to be discontinued for 2 weeks to allow TSH levels to rise before treatment. Levels >30 mU/L are considered optimal, based on noncontrolled studies. A low-iodine diet also is recommended during this |
Surgery_Schwartz_10892 | Surgery_Schwartz | to be discontinued for 2 weeks to allow TSH levels to rise before treatment. Levels >30 mU/L are considered optimal, based on noncontrolled studies. A low-iodine diet also is recommended during this 2-week period. The usual protocol involved administering a screening dose of 1 to 3 mCi and measuring uptake 24 hours later. After a total thy-roidectomy, this value should be <1%. A “hot” spot in the neck after initial screening usually represents residual normal tissue in the thyroid bed. Some investigators recommend omitting the scanning dose altogether to minimize thyrocyte “stunning” and subsequent requirement for higher treatment doses. Others recommend scanning only if the size of the remnant cannot be determined by the operative report or ultrasound, or if the results would alter the decision to treat or the dose to be administered. Current guidelines recommend using either 123I or low-activity 131I (1to 3-mCi dose) and delivering a therapeutic dose within 72 hours.The recommended | Surgery_Schwartz. to be discontinued for 2 weeks to allow TSH levels to rise before treatment. Levels >30 mU/L are considered optimal, based on noncontrolled studies. A low-iodine diet also is recommended during this 2-week period. The usual protocol involved administering a screening dose of 1 to 3 mCi and measuring uptake 24 hours later. After a total thy-roidectomy, this value should be <1%. A “hot” spot in the neck after initial screening usually represents residual normal tissue in the thyroid bed. Some investigators recommend omitting the scanning dose altogether to minimize thyrocyte “stunning” and subsequent requirement for higher treatment doses. Others recommend scanning only if the size of the remnant cannot be determined by the operative report or ultrasound, or if the results would alter the decision to treat or the dose to be administered. Current guidelines recommend using either 123I or low-activity 131I (1to 3-mCi dose) and delivering a therapeutic dose within 72 hours.The recommended |
Surgery_Schwartz_10893 | Surgery_Schwartz | to treat or the dose to be administered. Current guidelines recommend using either 123I or low-activity 131I (1to 3-mCi dose) and delivering a therapeutic dose within 72 hours.The recommended dose of RAI is 30 mCi if remnant abla-tion is performed after total thyroidectomy for ATA low-risk thyroid or intermediate-risk cancer with lower risk features (i.e., low-volume central neck nodal metastases with no other known gross residual disease or any other adverse features). If RAI is given for adjuvant treatment to treat suspected microscopic dis-ease (in the absence of metastatic disease), doses ranging from 30 to 150 mCi are recommended, and there is no solid evidence to show that higher doses reduce the recurrence rates for T3 and N1 disease in this setting.If patients have an elevated Tg level, but negative RAI scan on follow-up, some physicians recommend treating once with 100 mCi of 131I and repeating the imaging 1 to 2 weeks later. Approximately one-third of these patients | Surgery_Schwartz. to treat or the dose to be administered. Current guidelines recommend using either 123I or low-activity 131I (1to 3-mCi dose) and delivering a therapeutic dose within 72 hours.The recommended dose of RAI is 30 mCi if remnant abla-tion is performed after total thyroidectomy for ATA low-risk thyroid or intermediate-risk cancer with lower risk features (i.e., low-volume central neck nodal metastases with no other known gross residual disease or any other adverse features). If RAI is given for adjuvant treatment to treat suspected microscopic dis-ease (in the absence of metastatic disease), doses ranging from 30 to 150 mCi are recommended, and there is no solid evidence to show that higher doses reduce the recurrence rates for T3 and N1 disease in this setting.If patients have an elevated Tg level, but negative RAI scan on follow-up, some physicians recommend treating once with 100 mCi of 131I and repeating the imaging 1 to 2 weeks later. Approximately one-third of these patients |
Surgery_Schwartz_10894 | Surgery_Schwartz | Tg level, but negative RAI scan on follow-up, some physicians recommend treating once with 100 mCi of 131I and repeating the imaging 1 to 2 weeks later. Approximately one-third of these patients demonstrate uptake on posttreatment imaging, and Tg levels usually decrease in these patients, documenting therapeutic benefit. The maxi-mum dose of radioiodine that can be administered at one time without performing dosimetry is approximately 200 mCi with a cumulative dose of 1000 to 1500 mCi. Up to 500 mCi can be given with proper pretreatment dosimetry. Recent studies also Brunicardi_Ch38_p1625-p1704.indd 165201/03/19 11:21 AM 1653THYROID, PARATHYROID, AND ADRENALCHAPTER 38Initial medical therapyall recurrencesNoneT4 aloneP< .05403530252015105P< .0001Years after initial therapyPercent cancer recurrences605040302010004035302520151050NoneT4 + RAI T4 alone T4 + RAI remnant | Surgery_Schwartz. Tg level, but negative RAI scan on follow-up, some physicians recommend treating once with 100 mCi of 131I and repeating the imaging 1 to 2 weeks later. Approximately one-third of these patients demonstrate uptake on posttreatment imaging, and Tg levels usually decrease in these patients, documenting therapeutic benefit. The maxi-mum dose of radioiodine that can be administered at one time without performing dosimetry is approximately 200 mCi with a cumulative dose of 1000 to 1500 mCi. Up to 500 mCi can be given with proper pretreatment dosimetry. Recent studies also Brunicardi_Ch38_p1625-p1704.indd 165201/03/19 11:21 AM 1653THYROID, PARATHYROID, AND ADRENALCHAPTER 38Initial medical therapyall recurrencesNoneT4 aloneP< .05403530252015105P< .0001Years after initial therapyPercent cancer recurrences605040302010004035302520151050NoneT4 + RAI T4 alone T4 + RAI remnant |
Surgery_Schwartz_10895 | Surgery_Schwartz | therapyall recurrencesNoneT4 aloneP< .05403530252015105P< .0001Years after initial therapyPercent cancer recurrences605040302010004035302520151050NoneT4 + RAI T4 alone T4 + RAI remnant ablation34/16315/230101/78922/1120/13551/6035/823/10217/4621/661/847/3782/541/6710/3264/390/386/2290/250/2610/1350/130/181/51Initial medical therapydistant recurrencesNoneT4 aloneP<.0002P<.02Years after initial therapyPercent distant recurrence35302520151050None 8/163 9/112 3/82 0/66 1/54 4/39 0/25 0/13T4 alone 19/789 15/603 7/462 0/378 2/326 4/229 8/135 1/51T4 + RAI 2/230 0/135 1/102 0/84 1/67 0/38 0/26 0/11T4 + RAI remnant ablationABFigure 38-19. Tumor recurrence at a median of 16.7 years after thyroid surgery. The numerator is the number of patients with recurrence, and the denominator is the number of patients in each time interval. The P values | Surgery_Schwartz. therapyall recurrencesNoneT4 aloneP< .05403530252015105P< .0001Years after initial therapyPercent cancer recurrences605040302010004035302520151050NoneT4 + RAI T4 alone T4 + RAI remnant ablation34/16315/230101/78922/1120/13551/6035/823/10217/4621/661/847/3782/541/6710/3264/390/386/2290/250/2610/1350/130/181/51Initial medical therapydistant recurrencesNoneT4 aloneP<.0002P<.02Years after initial therapyPercent distant recurrence35302520151050None 8/163 9/112 3/82 0/66 1/54 4/39 0/25 0/13T4 alone 19/789 15/603 7/462 0/378 2/326 4/229 8/135 1/51T4 + RAI 2/230 0/135 1/102 0/84 1/67 0/38 0/26 0/11T4 + RAI remnant ablationABFigure 38-19. Tumor recurrence at a median of 16.7 years after thyroid surgery. The numerator is the number of patients with recurrence, and the denominator is the number of patients in each time interval. The P values |
Surgery_Schwartz_10896 | Surgery_Schwartz | recurrence at a median of 16.7 years after thyroid surgery. The numerator is the number of patients with recurrence, and the denominator is the number of patients in each time interval. The P values are derived from log-rank statistical analysis of 40-year life-table data. Figure shows that all recurrences (A) and distant metastases (B) were reduced in patients who received radioactive iodine (RAI) in addition to thyroxine (T4) therapy. (Reproduced with permission from Mazzaferri E, Kloos R: Current approaches to primary therapy for papillary and follicular thyroid cancer, Clin Endocrinol Metab. 2001 Apr;86(4):1447-1363.)Brunicardi_Ch38_p1625-p1704.indd 165301/03/19 11:21 AM 1654SPECIFIC CONSIDERATIONSPART IIshow an increase in the number of second cancers in patients treated with RAI.51 The early and delayed complications of RAI therapy are listed in Table 38-7.Thyroid Hormone T4 is necessary as replacement therapy in patients after total or near-total thyroidectomy, and also has | Surgery_Schwartz. recurrence at a median of 16.7 years after thyroid surgery. The numerator is the number of patients with recurrence, and the denominator is the number of patients in each time interval. The P values are derived from log-rank statistical analysis of 40-year life-table data. Figure shows that all recurrences (A) and distant metastases (B) were reduced in patients who received radioactive iodine (RAI) in addition to thyroxine (T4) therapy. (Reproduced with permission from Mazzaferri E, Kloos R: Current approaches to primary therapy for papillary and follicular thyroid cancer, Clin Endocrinol Metab. 2001 Apr;86(4):1447-1363.)Brunicardi_Ch38_p1625-p1704.indd 165301/03/19 11:21 AM 1654SPECIFIC CONSIDERATIONSPART IIshow an increase in the number of second cancers in patients treated with RAI.51 The early and delayed complications of RAI therapy are listed in Table 38-7.Thyroid Hormone T4 is necessary as replacement therapy in patients after total or near-total thyroidectomy, and also has |
Surgery_Schwartz_10897 | Surgery_Schwartz | The early and delayed complications of RAI therapy are listed in Table 38-7.Thyroid Hormone T4 is necessary as replacement therapy in patients after total or near-total thyroidectomy, and also has the additional effect of suppressing TSH and reducing the growth stimulus for any possible residual thyroid cancer cells. TSH suppression reduces tumor recurrence rates. Current guidelines advise maintaining initial TSH levels <0.1 mU/mL in patients with high-risk thyroid cancer and in the range of 0.1 to 0.5 mU/mL in patients with intermediate-risk disease. For low-risk patients (with or without remnant ablation) with undetectable serum Tg levels, TSH levels can be maintained at the lower end of the reference range (0.5–2 mU/L). If these patients have low measureable Tg levels, it is recommended that TSH be maintained at or slightly below lower limit of normal (0.1 to 0.5 mU/L) while continuing surveillance for recurrence. In low-risk patients treated with lobectomy alone, it is advised | Surgery_Schwartz. The early and delayed complications of RAI therapy are listed in Table 38-7.Thyroid Hormone T4 is necessary as replacement therapy in patients after total or near-total thyroidectomy, and also has the additional effect of suppressing TSH and reducing the growth stimulus for any possible residual thyroid cancer cells. TSH suppression reduces tumor recurrence rates. Current guidelines advise maintaining initial TSH levels <0.1 mU/mL in patients with high-risk thyroid cancer and in the range of 0.1 to 0.5 mU/mL in patients with intermediate-risk disease. For low-risk patients (with or without remnant ablation) with undetectable serum Tg levels, TSH levels can be maintained at the lower end of the reference range (0.5–2 mU/L). If these patients have low measureable Tg levels, it is recommended that TSH be maintained at or slightly below lower limit of normal (0.1 to 0.5 mU/L) while continuing surveillance for recurrence. In low-risk patients treated with lobectomy alone, it is advised |
Surgery_Schwartz_10898 | Surgery_Schwartz | that TSH be maintained at or slightly below lower limit of normal (0.1 to 0.5 mU/L) while continuing surveillance for recurrence. In low-risk patients treated with lobectomy alone, it is advised to keep TSH in the mid to lower reference range (0.5–2 mU/L), and hor-mone therapy may be needed to maintain these levels. Further TSH suppression levels are determined by response to therapy. The risk of tumor recurrence must be balanced with the side effects associated with prolonged TSH suppression, including osteopenia and cardiac problems, particularly in older patients.Follow-Up of Patients With Differentiated Thyroid Cancer Thyroglobulin Measurement Tg and anti-Tg antibody levels should be measured initially at 6 to 12 month intervals and more frequently in patients with high-risk tumors. Further measure-ments are guided by response to therapy. Patients are considered to have an excellent response to treatment if suppressed Tg is <0.2 ng/mL and stimulated Tg is <1 ng/mL with negative | Surgery_Schwartz. that TSH be maintained at or slightly below lower limit of normal (0.1 to 0.5 mU/L) while continuing surveillance for recurrence. In low-risk patients treated with lobectomy alone, it is advised to keep TSH in the mid to lower reference range (0.5–2 mU/L), and hor-mone therapy may be needed to maintain these levels. Further TSH suppression levels are determined by response to therapy. The risk of tumor recurrence must be balanced with the side effects associated with prolonged TSH suppression, including osteopenia and cardiac problems, particularly in older patients.Follow-Up of Patients With Differentiated Thyroid Cancer Thyroglobulin Measurement Tg and anti-Tg antibody levels should be measured initially at 6 to 12 month intervals and more frequently in patients with high-risk tumors. Further measure-ments are guided by response to therapy. Patients are considered to have an excellent response to treatment if suppressed Tg is <0.2 ng/mL and stimulated Tg is <1 ng/mL with negative |
Surgery_Schwartz_10899 | Surgery_Schwartz | Further measure-ments are guided by response to therapy. Patients are considered to have an excellent response to treatment if suppressed Tg is <0.2 ng/mL and stimulated Tg is <1 ng/mL with negative imag-ing. In these patients, Tg levels can be followed every 12 to 24 months while on thyroid hormone as their risk of recurrence is low (1–4%). Patients with structurally or biochemically incomplete (negative imaging but suppressed Tg ≥1 ng/mL or stimulated Tg ≥10 ng/mL or rising anti-Tg levels) or indeter-minate responses (nonspecific imaging findings, suppressed Tg detectable but <1 ng/mL, and stimulated Tg detectable but <10 ng/mL or stable or declining anti-Tg levels) require addi-tional investigations.40 Tg measurements in FNAB aspirates have also been shown to be useful in the detection of nodal metastatic disease.52Imaging After the first posttreatment scan, lowand some intermediate-risk patients with negative TSH-stimulated Tg and cervical ultrasound do not require routine | Surgery_Schwartz. Further measure-ments are guided by response to therapy. Patients are considered to have an excellent response to treatment if suppressed Tg is <0.2 ng/mL and stimulated Tg is <1 ng/mL with negative imag-ing. In these patients, Tg levels can be followed every 12 to 24 months while on thyroid hormone as their risk of recurrence is low (1–4%). Patients with structurally or biochemically incomplete (negative imaging but suppressed Tg ≥1 ng/mL or stimulated Tg ≥10 ng/mL or rising anti-Tg levels) or indeter-minate responses (nonspecific imaging findings, suppressed Tg detectable but <1 ng/mL, and stimulated Tg detectable but <10 ng/mL or stable or declining anti-Tg levels) require addi-tional investigations.40 Tg measurements in FNAB aspirates have also been shown to be useful in the detection of nodal metastatic disease.52Imaging After the first posttreatment scan, lowand some intermediate-risk patients with negative TSH-stimulated Tg and cervical ultrasound do not require routine |
Surgery_Schwartz_10900 | Surgery_Schwartz | of nodal metastatic disease.52Imaging After the first posttreatment scan, lowand some intermediate-risk patients with negative TSH-stimulated Tg and cervical ultrasound do not require routine diagnostic whole-body radioiodine scans. However, diagnostic whole-body scans 6 to 12 months after remnant ablation may be of value in the follow-up of patients with highor intermediate-risk patients with higher risk features. Other scenarios for follow-up scans include patients with abnormal uptake outside the thyroid bed on posttherapy scan, those with poorly informative postablation scans (e.g., due to high thyroid bed uptake), and patients with Tg antibodies.Cervical ultrasound be performed to evaluate the thyroid bed and central and lateral cervical nodal compartments at 6 and 12 months after thyroidectomy and then annually for at least 3 to 5 years, depending on the patient’s risk for recurrent disease and Tg status. Sonographically suspicious nodes ≥8 to 10 mm on the smallest diameter | Surgery_Schwartz. of nodal metastatic disease.52Imaging After the first posttreatment scan, lowand some intermediate-risk patients with negative TSH-stimulated Tg and cervical ultrasound do not require routine diagnostic whole-body radioiodine scans. However, diagnostic whole-body scans 6 to 12 months after remnant ablation may be of value in the follow-up of patients with highor intermediate-risk patients with higher risk features. Other scenarios for follow-up scans include patients with abnormal uptake outside the thyroid bed on posttherapy scan, those with poorly informative postablation scans (e.g., due to high thyroid bed uptake), and patients with Tg antibodies.Cervical ultrasound be performed to evaluate the thyroid bed and central and lateral cervical nodal compartments at 6 and 12 months after thyroidectomy and then annually for at least 3 to 5 years, depending on the patient’s risk for recurrent disease and Tg status. Sonographically suspicious nodes ≥8 to 10 mm on the smallest diameter |
Surgery_Schwartz_10901 | Surgery_Schwartz | thyroidectomy and then annually for at least 3 to 5 years, depending on the patient’s risk for recurrent disease and Tg status. Sonographically suspicious nodes ≥8 to 10 mm on the smallest diameter measurement should be biopsied for cytology as well as Tg measurement in the aspirate washout. Smaller nodes can be followed and biopsied if there is contin-ued growth. FDG-PET and PET-CT scans have been shown to be useful to localize recurrent or persistent thyroid cancer in patients who have Tg-positive, RAI scan–negative disease. FDG-PET can also be useful for the initial staging of patients with poorly differentiated thyroid carcinomas or Hürthle cell tumors, particularly in patients with other evidence of disease on imaging or Tg levels. In addition, they may be used as a prog-nostic tool in patients with metastatic disease and to evaluate the response to treatment in patients with metastatic or locally advanced disease.Additional Treatment Modalities Radiotherapy, Thermal Ablation, | Surgery_Schwartz. thyroidectomy and then annually for at least 3 to 5 years, depending on the patient’s risk for recurrent disease and Tg status. Sonographically suspicious nodes ≥8 to 10 mm on the smallest diameter measurement should be biopsied for cytology as well as Tg measurement in the aspirate washout. Smaller nodes can be followed and biopsied if there is contin-ued growth. FDG-PET and PET-CT scans have been shown to be useful to localize recurrent or persistent thyroid cancer in patients who have Tg-positive, RAI scan–negative disease. FDG-PET can also be useful for the initial staging of patients with poorly differentiated thyroid carcinomas or Hürthle cell tumors, particularly in patients with other evidence of disease on imaging or Tg levels. In addition, they may be used as a prog-nostic tool in patients with metastatic disease and to evaluate the response to treatment in patients with metastatic or locally advanced disease.Additional Treatment Modalities Radiotherapy, Thermal Ablation, |
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