Anaplastic Thyroid Carcinoma

Abstract

A thyroidectomy was performed for a rapidly enlarging neck mass in a woman in her 70s. The tumor was diagnosed by pathology as an anaplastic thyroid carcinoma. Which of the following statements regarding anaplastic thyroid carcinoma is most accurate?a.Anaplastic thyroid carcinoma is a highly aggressive malignancy that usually occurs in persons in their second to third decade of life.b.Almost all anaplastic thyroid carcinomas occur in the setting of previous radiation to the neck.c.Anaplastic thyroid carcinomas are highly aggressive malignancies, usually fatal, and affect older persons.d.Anaplastic thyroid carcinomas may be associated with BRAF or RAS mutations but are not associated with TP53 or TERT promoter mutations. Answer: c. Anaplastic thyroid carcinomas are highly aggressive malignancies, usually fatal, and affect older persons. Anaplastic thyroid carcinoma is a highly aggressive thyroid malignancy composed of undifferentiated follicular thyroid cells. These tumors are uncommon, accounting for 1% of thyroid carcinomas in the United States.1Pereira M. Williams V.L. Hallanger Johnson J. Valderrabano P. Thyroid cancer incidence trends in the United States: association with changes in professional guideline recommendations.Thyroid. 2020; 30: 1132-1140Crossref PubMed Scopus (36) Google Scholar Anaplastic thyroid carcinoma usually affects older persons (seventh decade), often presenting as a rapidly enlarging mass that may be associated with compressive symptoms and, in some cases, paraneoplastic manifestations. Anaplastic thyroid carcinoma is generally lethal, and 56% of patients have lymph-node metastases and 38% distant metastases at presentation.2Hvilsom G.B. Londero S.C. Hahn C.H. et al.Anaplastic thyroid carcinoma in Denmark 1996-2012: a national prospective study of 219 patients.Cancer Epidemiol. 2018; 53: 65-71Crossref PubMed Scopus (12) Google Scholar The tumors are highly infiltrative, often have extrathyroidal growth, angiolymphatic invasion, and high-grade nuclear features. A variety of histologic subtypes of anaplastic thyroid carcinoma occur such as epithelioid, spindle cell/sarcomatoid, paucicellular, squamous, giant cell, rhabdoid/rhabdomyoblastic among others (Figures), making the differential diagnosis challenging in some cases. Approximately 10% of these tumors are associated with history of radiation exposure or iodine deficiency, respectively. Anaplastic thyroid carcinomas may occur with a previous or concurrent well-differentiated or poorly differentiated thyroid carcinoma.3Lam K.Y. Lo C.Y. Chan K.W. Wan K.Y. Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21.Ann Surg. 2000; 231: 329-338Crossref PubMed Scopus (132) Google Scholar,4Xu B. Fuchs T. Dogan S. et al.Dissecting anaplastic thyroid carcinoma: a comprehensive clinical, histologic, immunophenotypic, and molecular study of 360 cases.Thyroid. 2020; 30: 1505-1517Crossref PubMed Scopus (57) Google Scholar Anaplastic thyroid carcinomas are described as having “early” and “late” genetic alterations. Early driver mutations often involve BRAF V600E (especially in tumors associated with papillary thyroid carcinoma) or RAS and late mutations involve TP53 and TERT promoter.5Volante M. Lam A.K. Papotti M. Tallini G. Molecular pathology of poorly differentiated and anaplastic thyroid cancer: what do pathologists need to know?.Endocr Pathol. 2021; 32: 63-76Crossref PubMed Scopus (13) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)