ArticleJournal of endocrinological investigation2026
Molecular and immunohistochemical characterization of cribriform-morular thyroid carcinoma: insights into its origin and therapeutic targets.
Article in Journal of endocrinological investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCribriform-morular thyroid carcinoma (CMTC) is a rare thyroid malignancy with distinctive morphology that occurs sporadically or in association with familial adenomatous polyposis. Despite known WNT/β-catenin pathway involvement, CMTC's cellular origin and therapeutic targets remain poorly characterized.
methodsFive CMTC cases diagnosed between 2012 and 2022 were retrospectively analyzed using next-generation sequencing and comprehensive immunohistochemical profiling to elucidate molecular characteristics and potential therapeutic targets.
resultsAll patients were young females (mean age 28 years, range 19-47) presenting with small tumors (mean 19.4 mm, range 7-28 mm) without lymph node metastasis. Histologically, all cases demonstrated characteristic cribriform and morular architecture. Nuclear β-catenin positivity was observed in four cases, while CD56 was expressed in all cases. Low-level HER2 expression was present across all tumors. Next-generation sequencing revealed somatic APC mutations in three cases, concurrent APC/CTNNB1 mutations in one case, and CTNNB1 mutations in both lobes of one case. High tumor mutational burden was detected in two cases.
conclusionsThe consistent presence of APC or CTNNB1 mutations coupled with CD56 positivity supports CMTC's origin from thyroid follicular epithelial cells that acquire an intestinal-like phenotype through characteristic genetic alterations. The presence of HER2 expression and high tumor mutational burden in a subset of cases identifies potential therapeutic targets for this rare malignancy.
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