Thyroid & parathyroid

• The most aggressive follicular cell derived thyroid malignancy composed of undifferentiated cells
• Total or near total loss of follicular cell differentiation
• Concomitant with previous history of differentiated thyroid carcinoma
• Clinically, a rapidly enlarging neck mass with survival < 6 months in most cases

• ICD-O: 8020/3 - carcinoma, undifferentiated, NOS
• ICD-10: C73 - malignant neoplasm of thyroid gland
• ICD-11: 2D10.3 - undifferentiated carcinoma of thyroid gland

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Contributed by Shipra Agarwal, M.D., Mark R. Wick, M.D. and AFIP


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Contributed by Shipra Agarwal, M.D., Shuanzeng Wei, M.D., Ph.D., Stephen J. Schultenover, M.D. and AFIP

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Contributed by Shipra Agarwal, M.D. and Ayana Suzuki, C.T.

• PAX8
  • Immunopositivity varies with the histologic pattern: up to 100% of the squamoid and 50 - 60% of the sarcomatoid (Semin Diagn Pathol 2015;32:305)
  • More likely to be positive in the presence of a DTC component
  • Higher rate of positivity (60 - 80%) with less specific polyclonal antibody (Hum Pathol 2011;42:1873)
  • ~50 - 60% when using monoclonal antibody (Virchows Arch 2020;476:431)
• Cytokeratin (50 - 70%) (Thyroid 2020;30:1505)
• Aberrant p53 expression (Thyroid 2020;30:1505)
• BRAF VE1 antibody detects BRAF V600E mutant protein (Cancers (Basel) 2020;12:596)
• Ki67 labeling index > 30%, often > 50%
• Epithelial membrane antigen and vimentin are frequently positive but have no role in diagnostic workup

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• Thyroid, total thyroidectomy:
  • Anaplastic thyroid carcinoma, epithelioid pattern, 12 cm, replacing the entire specimen (see synoptic report)
  • It is dedifferentiating from papillary thyroid carcinoma, classical subtype
  • Gross extrathyroidal extension into adjoining skeletal muscles
  • Multiple lymphovascular emboli and perineural invasion are present
  • 4 of the 5 lymph nodes dissected from the specimen are involved by tumor
  • AJCC stage IVB (pT3bN1Mx)
  • Immunohistochemically, the tumor cells are positive for pan-CK, PAX8, VE1 and p53 but are negative for TTF1 and TG; the Ki67 labeling index is 35%
  
  
• Thyroid, needle biopsy:
  • Anaplastic thyroid carcinoma, spindle cell pattern
  • Immunohistochemically, the tumor cells are positive for pan-CK, vimentin and p53 but are negative for PAX8, p40 and VE1; the Ki67 labeling index is 55%
  • Findings corroborate with but are not specific for the above diagnosis; a clinicoradiological correlation is advised
  
  
• Thyroid, fine needle cytology:
  • Malignant (Bethesda diagnostic category VI): anaplastic thyroid carcinoma, pleomorphic pattern
  • Immunohistochemistry performed on cell block shows that the tumor cells are positive for pan-CK and PAX8 but are negative for VE1
  • The findings corroborate with but are not specific for the above diagnosis; a clinicoradiological correlation is advised

A 72 year old woman presented with a hoarse voice and rapid enlargement of neck mass of 3 months' duration. Radiology revealed lumbar vertebral metastases. Cytological examination from the low anterior neck mass showed a tumor composed of mitotically active pleomorphic polygonal and spindle cells in a necrotic and inflammatory background. Incisional biopsy revealed a malignant spindle cell tumor. What is the most likely diagnosis?


1. Anaplastic thyroid carcinoma
2. Follicular thyroid carcinoma
3. Metastatic carcinoma to thyroid gland
4. Papillary thyroid carcinoma
5. Spindle epithelial tumor with thymus-like differentiation

A. Anaplastic thyroid carcinoma. Anaplastic thyroid carcinoma typically presents with a short duration history of a rapidly enlarging neck mass, with symptoms secondary to compression of adjacent structures, such as pain, dysphonia, dysphagia, dyspnea and cough. Lymph node and distant metastases are common. Cytological examination reveals a pleomorphic tumor cell population, including bizarre forms, dispersed in a necrotic and inflammatory background. Mitotic activity is frequent and atypical mitotic forms common. Answer B is incorrect because follicular thyroid carcinoma, on cytology, shows a microfollicular architecture and lacks marked cellular pleomorphism and extensive necrosis. Answer C is incorrect because the clinical presentation of hoarseness of voice, a rapidly enlarging neck mass and radiology revealing distant metastases are indicative of a thyroid primary. Answer D is incorrect because papillary thyroid carcinoma, on cytological evaluation, lacks cellular pleomorphism and extensive necrosis. Instead, classic papillary thyroid carcinoma shows follicular cells arranged as papillae, sheets and fragments showing typical nuclear features. Answer E is incorrect because spindle epithelial tumor with thymus-like elements is characterized by low grade spindle cells and an amyloid-like material with or without an epithelial component.

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Reference: Anaplastic thyroid carcinoma

B. TTF1 negative, thyroglobulin negative, PAX8 positive, cytokeratin positive. Anaplastic thyroid carcinoma (ATC) is usually immunonegative for TTF1 and thyroglobulin but expresses PAX8; cytokeratin is variably positive. Answer E is incorrect because vimentin can also be variably positive in ATC but in this case thyroglobulin is positive as well. Answer D is incorrect because calcitonin is immunopositive in medullary thyroid carcinoma. Answer A is incorrect because CD5 and CD117 are positive in intrathyroidal thymic carcinoma. Answer C is incorrect because S100 and HMB45 are positive in malignant melanoma.

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Reference: Anaplastic thyroid carcinoma