Authors
Mohammed Sayel Alorjani, Manuel Sobrinho-Simões, Ayat Nader Al-Oqaily, Dania Jamal Alsinglawi, Hussein Ali Heis, José Manuel Cameselle-Teijeiro
Published in
Virchows Archiv : an international journal of pathology. Jun 19, 2026. Epub Jun 19, 2026.
Abstract
Cribriform morular thyroid carcinoma (CMTC) is a rare neoplasm more common in young euthyroid females, usually associated with familial adenomatous polyposis (FAP) syndrome, but also presenting as sporadic cases. These tumors result from the activation of the WNT/β-catenin signaling pathway, usually through germline APC gene mutations in FAP-associated disease, while sporadic cases may exhibit somatic mutations in APC, CTNNB1, and AXIN1. Additional possible molecular events include somatic mutations in KRAS, PIK3CA, KMT2C, KMT2D, TERT promoter or RET rearrangements. BRAF mutations do not occur. We describe a sporadic case of high-grade CMTC presented in a 44-year-old female with a large multilobulated, unifocal mass in the right thyroid lobe. The tumor showed the typical cribriform and morular patterns, high grade features (Ki-67 proliferative index of 20% and foci of necrosis), marked vascular invasion and regional lymph node metastases. The tumor cells were immunoreactive for keratin (KRT) clone CKAE1/AE3, KRT7, and TTF1/NKX2, with aberrant (nuclear and cytoplasmic) expression of β-catenin, but negative for thyroglobulin and calcitonin. CDX2 was detected exclusively in the morular structures. The somatic APC p.(Thr621Leufs*9) oncogenic variant and the somatic TERT promoter - 124 (C228T) oncogenic variant were found, in line with the tumor type and tumor grade respectively; but, for the first time, EWSR1 gene rearrangement was also detected, expanding the molecular spectrum of this uncommon entity.
PMID:
42315752
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.
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