Related Experiment Video
Updated: Aug 6, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Molecular and immunohistochemical characterization of cribriform-morular thyroid carcinoma: insights into its origin
Joo Yeon Koo1, Ji Young Lee1, Nah Ihm Kim2
1Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, 264 Seoyang-ro, Hwasun, 58128, South Korea.
Background:
Cribriform-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.
Methods:
Five 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.
Results:
All 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.
Conclusions:
The 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.
