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Thyroid and Parathyroid John K 38419 Weidner (SAUNM) RIGHT INTERACTIVE 44 Thyroid and Parathyroid John K. C. Chan The Thyroid Gland NON-NEOPLASTIC LESIONS NEOPLASTIC LESIONS Incidental and Insignificant Findings in the Thyroid Classification Gland General Considerations Cysts Follicular Adenoma Thyroid Tissue in the Lateral Neck Follicular Carcinoma Thyroiditis Papillary Carcinoma Graves’ Disease Poorly Differentiated Thyroid Carcinoma Nodular Goiter Anaplastic (Undifferentiated) Carcinoma Dyshormonogenetic Goiter Columnar Cell Carcinoma Fine-Needle Aspiration–Associated Changes in the Mucoepidermoid Carcinoma Thyroid Gland Sclerosing Mucoepidermoid Carcinoma with Amyloid Goiter Eosinophilia Black Thyroid Mucinous Carcinoma Uncommon Lesions of the Thyroid Gland Medullary Thyroid Carcinoma The Parathyroid Gland Collision Tumor NEOPLASTIC LESIONS Mixed Follicular-Parafollicular Carcinoma Classification Thymic and Related Branchial Pouch Tumors of the General Considerations Thyroid Parathyroid Adenoma Intrathyroid Parathyroid Tumor Parathyroid Carcinoma Malignant Lymphoma Contents of the Final Surgical Pathology Report Plasmacytoma of the Thyroid NON-NEOPLASTIC LESIONS Langerhans Cell Histiocytosis (Histiocytosis X) Primary Parathyroid Chief Cell Hyperplasia Angiosarcoma Primary Water-Clear Cell Hyperplasia Solitary Fibrous Tumor Secondary Parathyroid Hyperplasia Other Mesenchymal Tumors Parathyroid Cyst Paraganglioma Periparathyroid Salivary Heterotopia–Cyst Unit Teratoma Amyloidosis Metastatic Malignant Neoplasms in Thyroid Contents of the Final Surgical Pathology Report A. The Thyroid Gland NEOPLASTIC LESIONS Tumors of Thyroid Follicular Epithelium Classification Follicular adenoma, including Hu¨ rthle cell ade- noma The primary tumors of the thyroid gland, grouped Follicular carcinoma, including Hu¨ rthle cell car- according to the line of differentiation, include the cinoma following.1 Papillary carcinoma short standard 3 long Copyright ᭧ 2003, Elsevier Science (USA). All rights Reserved 4 38419 Weidner (SAUNM) LEFT INTERACTIVE TABLE 44–1. Immunohistochemical Staining Profile of the Various Thyroid Neoplasms Pan-neuroendocrine Markers Copyright (such as synaptophysin, Thyroid Transcription Tumor Type Cytokeratin chromogranin) Thyroglobulin Calcitonin Factor 1 Other Markers Papillary carcinoma; follicular Positive Negative Positive Negative Positive — ᭧ adenoma-carcinoma; poorly 2003, Elsevier Science (USA). All rights Reserved differentiated thyroid carci- noma; columnar cell carci- noma Medullary carcinoma Positive Positive Negative Positive Positive Carcinoembryonic an- tigen (CEA)ϩ; S-100ϩ sustentacular cells may be present in hereditary form Mixed follicular-parafollicular Positive Positive Positive Positive Positive — carcinoma Anaplastic carcinoma Variable (positive in ϳ50% Negative Negative Negative Usually negative — of cases) Angiosarcoma Variable (usually negative, Negative Negative Negative Negative Positive for endothe- but sometimes positive) lial markers, such as CD31, CD34, factor VIII Malignant lymphoma Negative Negative Negative Negative Negative Leukocyte common antigenϩ and other lymphoid markersϩ Carcinoma showing thymus- Positive Negative Negative Negative Negative CD5ϩ like element (CASTLE) Intrathyroid parathyroid tumor Positive Positive Negative Negative Negative Parathyroid hormoneϩ Paraganglioma Negative Positive Negative Negative Negative S-100ϩ sustentacular cells; CEAϪ long standard short top of RH 38419 Weidner (SAUNM) RIGHT INTERACTIVE Thyroid and Parathyroid 5 top of RH Poorly differentiated thyroid carcinoma, includ- documented factor.6 External radiation was once ing insular carcinoma popularly used to treat patients with a variety of Anaplastic carcinoma, squamous cell carcinoma, benign disorders of the head and neck region, such and carcinosarcoma as acne, tinea capitis, cervical tuberculous lymphad- Rare tumor types: columnar cell carcinoma, mu- enitis, and thymic enlargement; such patients have coepidermoid carcinoma, sclerosing muco- an increased chance of developing thyroid cancer. epidermoid carcinoma with eosinophilia, Cancer patients treated with radiation have been mucinous carcinoma shown to have an excess of thyroid cancer com- pared with control subjects. Survivors of the Hiro- Tumors Showing C Cell or shima atomic bomb have a high risk for develop- Simultaneous Follicular and C Cell ment of thyroid cancer; persons who were younger Differentiation than 10 years when they were exposed have an ex- cess relative risk of 9.46. The Chernobyl nuclear ac- Medullary carcinoma cident in 1986 provides further evidence of the im- Collision tumor: follicular and medullary carci- portance of radiation in thyroid carcinogenesis; in nomas or papillary and medullary carcino- some exposed areas, the incidence of thyroid cancer mas in children increased from 0.5 per million per year Mixed follicular-parafollicular carcinoma (differ- to 96.4 per million per year. The clinicopathologic entiated thyroid carcinoma, intermediate features of the Chernobyl accident–associated thy- type) roid cancers are listed in Table 44–2. Ectopic Tumors Iodine deficiency and endemic goiter are associ- ated with an increased risk of thyroid carcinoma Ectopic thymoma and angiosarcoma. It has been postulated that the Spindle epithelial tumor with thymus-like ele- tumors may result from prolonged stimulation of ment (SETTLE) the thyroid tissues by thyroid-stimulating hormone.7 Carcinoma showing thymus-like element (CAS- Hashimoto’s thyroiditis and lymphocytic thy- TLE) roiditis are associated with an increased risk for ma- Intrathyroid parathyroid adenoma and carci- lignant lymphoma. In addition, sclerosing mucoepi- noma dermoid carcinoma with eosinophilia almost always arises in a setting of fibrosing Hashimoto’s thyroidi- Tumors of Hematolymphoid Cells tis. Hashimoto’s thyroiditis may slightly increase the risk for development of papillary carcinoma.8 Malignant lymphoma Plasmacytoma Langerhans cell histiocytosis Mesenchymal and Other Tumors TABLE 44–2. Features of Chernobyl Nuclear Accident- Benign and malignant mesenchymal tumors, Associated Thyroid Cancer such as solitary fibrous tumor, smooth mus- cle tumor, peripheral nerve sheath tumor, It is caused by exposure to radioactive iodine fallout; the acci- dent occurred on April 26, 1986. angiosarcoma Most cases are papillary carcinomas (ϳ95%). The papillary car- Paraganglioma cinomas often show a follicular, solid, or mixed follicular- Teratoma papillary-solid pattern, contrasting with the typical papillary pattern seen in sporadic papillary carcinomas in children. The most common primary thyroid cancer is The incidence of thyroid cancer in areas around Chernobyl has papillary carcinoma, which accounts for 60% to 80% increased 6- to 500-fold compared with previous years, de- of all cases, followed by follicular carcinoma, which pending on the distance from the accident site. The greatest number of cases occur in areas where the thyroid radiation accounts for 10% to 20% of cases. Most thyroid tu- dose is Ն0.5 gy. mors can be readily diagnosed on morphologic as- The tumors show greater aggressiveness at presentation, such sessment alone. Nonetheless, in some circumstances, as extrathyroidal extension, venous invasion, and lymph especially with medullary carcinoma or unusual- node metastasis. Thus, treatment often entails total thyroid- looking tumors, immunohistochemical studies are ectomy and lymph node dissection. Lymphocytic thyroiditis and antithyroperoxidase antibody are required for a definitive classification. The immuno- more common than in sporadic cases. histochemical profiles of the more common thyroid Age at diagnosis is usually Յ14 years, which is younger than tumors are shown in Table 44–1.2–5 for the sporadic thyroid cancers in children not related to a nuclear accident. The time interval between the nuclear accident and the diag- nosis of thyroid cancer is ϳ6–7 years. General Considerations Subjects younger than 5 years or in utero at the time of the nuclear accident account for the majority of cases. PATHOGENESIS Papillary carcinomas occurring in this setting show a much higher frequency of RET/PTC (especially RET/PTC3) gene rear- Some risk factors for development of thyroid cancer rangement compared with sporadic cases. short have been identified; radiation exposure is the best standard long Copyright ᭧ 2003, Elsevier Science (USA). All rights Reserved 38419 Weidner (SAUNM) LEFT INTERACTIVE 6 Endocrine System top of RH Thyroid cancer can occur as a component of component of Cowden’s disease and may include some heritable syndromes.8, 9 Medullary carcinoma follicular adenoma, follicular carcinoma, and papil- is a key component of multiple endocrine neoplasia lary carcinoma. There are also less well defined fa- type 2 (MEN 2) or familial medullary thyroid carci- milial nonmedullary thyroid cancer syndromes. noma. Thyroid adenoma or carcinoma sometimes occurs as a component of MEN type 1 (MEN 1). GRADING AND STAGING Some patients with familial adenomatous polyposis The TNM staging is the most widely used staging develop thyroid cancer, most commonly papillary system for thyroid cancer (Table 44–3). There are no carcinoma of the cribriform-morular variant (so- universally accepted grading systems for thyroid called familial adenomatous polyposis–associated cancers, although the histologic grade may be im- thyroid carcinoma). Thyroid tumors also constitute a plied from the histologic type (e.g., low grade for TABLE 44–3. Staging of Thyroid Tumors TNM Staging Primary Tumor (T) All categories
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