High-grade cribriform morular thyroid carcinoma: A clinicopathologic analysis of six patients and a review of the literature.

Cribriform morular thyroid carcinoma was formally considered a subtype of papillary thyroid carcinoma due to its architecture and nuclear features. The genomic landscape and immunophenotype of cribriform morular thyroid carcinoma are distinct from papillary thyroid carcinoma. Given this constellation of findings, questions were raised regarding its histogenesis and the 5th edition of the WHO endocrine and neuroendocrine tumors placed cribriform morular thyroid carcinoma in the thyroid tumors of uncertain histogenesis category. This distinction excludes cribriform morular thyroid carcinoma from the high-grade follicular cell-derived non-anaplastic thyroid carcinoma. Thus, we sought to investigate if the criteria for differentiated high-grade thyroid carcinoma would be applicable to cribriform morular thyroid carcinoma tumor category. Herein, we report six patients with high-grade cribriform morular thyroid carcinoma and review of the literature for additional patients. There are at least 10 probable high-grade cribriform morular thyroid carcinomas in the English literature. The study population included 5 females and 1 male aged 19-48 years (median 34.5 years). Two patients had documented syndromes Familial adenomatous polyposis and Gardner syndrome. One patient presented with distant metastatic disease while four patients recurred with distant metastatic disease. Three patients had pathogenic alterations involving the APC gene and one patient had a pathogenic CTNNB1 alteration. Two cases had pathogenic alterations in genes associated with aggressive thyroid carcinoma: TERT and PIK3CA. In this limited series only one patient died of disease. Even so, three were alive with disease at distant metastatic sites. Whether this is a consistent finding in this tumor category remains to be addressed as more patient series are published.