Oncocytic Poorly Differentiated Thyroid Carcinoma

A woman in her 60s with a history of thyroid cancer presented with a neck mass. The resection revealed a nonanaplastic oncocytic thyroid carcinoma invading the skin with increased mitotic activity and loss of the follicular growth pattern (Figure). The immunophenotype supported thyroidal origin. Which of the following is true about poorly differentiated thyroid carcinoma?a.The patients affected by poorly differentiated thyroid cancers are typically younger than those who have conventional well-differentiated thyroid carcinomas.b.Poorly differentiated thyroid cancer is an aggressive subtype of thyroid carcinoma with a prognosis intermediate between well-differentiated carcinomas of follicular cell origin and anaplastic thyroid carcinoma.c.Poorly differentiated thyroid cancer usually does not express epithelial markers or markers associated with thyroidal origin.d.Early molecular driver events of poorly differentiated thyroid cancer are mostly related to RET mutations. Answer: b. Poorly differentiated thyroid cancer is an aggressive subtype of thyroid carcinoma with a prognosis intermediate between well-differentiated carcinomas of follicular cell origin and anaplastic thyroid carcinoma. High-grade follicular cell–derived nonanaplastic thyroid carcinomas develop in older patients compared with conventional well-differentiated thyroid carcinomas. Poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma are both classified by the World Health Organization under the category of high-grade follicular cell–derived nonanaplastic thyroid carcinoma.1WHO Classification of Tumours Editorial BoardEndocrine and Neuroendocrine Tumours. International Agency for Research on Cancer.in: 5th ed, vol 10. WHO Classification of Tumours Series. 2022https://publications.iarc.frDate accessed: November 1, 2023Google Scholar The loss of the distinctive follicular growth pattern supports the designation of poorly differentiated thyroid carcinoma rather than differentiated high-grade thyroid carcinoma, which retains its distinctive architectural follicular growth pattern. The 3-year, 5-year, 10-year, and 20-year disease-specific survival rates are 89%, 76%, 60%, and 35%, respectively, and distant metastatic disease develops in 33% to 48% of patients.2Xu B. David J. Dogan S. et al.Primary high-grade non-anaplastic thyroid carcinoma: a retrospective study of 364 cases.Histopathology. 2022; 80: 322-337Crossref PubMed Scopus (37) Google Scholar, 3Rivera M. Ricarte-Filho J. Patel S. et al.Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study.Hum Pathol. 2010; 41: 172-180Crossref PubMed Scopus (61) Google Scholar, 4Thompson L.D. High grade differentiated follicular cell–derived thyroid carcinoma versus poorly differentiated thyroid carcinoma: a clinicopathologic analysis of 41 cases.Endocr Pathol. 2023; 34: 234-246Crossref PubMed Scopus (5) Google Scholar Retention of epithelial markers and markers associated with thyroidal origin is typical of high-grade follicular cell–derived nonanaplastic thyroid carcinomas, whereas decreased expression of these markers is expected in anaplastic thyroid carcinoma.1WHO Classification of Tumours Editorial BoardEndocrine and Neuroendocrine Tumours. International Agency for Research on Cancer.in: 5th ed, vol 10. WHO Classification of Tumours Series. 2022https://publications.iarc.frDate accessed: November 1, 2023Google Scholar,5Landa I. Ibrahimpasic T. Boucai L. et al.Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.J Clin Invest. 2016; 126: 1052-1066Crossref PubMed Scopus (809) Google Scholar Early molecular driver events are mostly related to RAS and BRAF p.V600E mutations, whereas RET mutations are associated with medullary thyroid carcinoma.1WHO Classification of Tumours Editorial BoardEndocrine and Neuroendocrine Tumours. International Agency for Research on Cancer.in: 5th ed, vol 10. WHO Classification of Tumours Series. 2022https://publications.iarc.frDate accessed: November 1, 2023Google Scholar,5Landa I. Ibrahimpasic T. Boucai L. et al.Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.J Clin Invest. 2016; 126: 1052-1066Crossref PubMed Scopus (809)