Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review)

Cameselle‑García,Soledad; Abdulkader‑Nallib,Ihab; Sánchez‑Ares,María; Cameselle‑Teijeiro,José Manuel

doi:10.3892/or.2024.8778

September-2024 Volume 52 Issue 3

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September-2024 Volume 52 Issue 3

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Review Open Access

Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review)

Authors:
- Soledad Cameselle‑García
- Ihab Abdulkader‑Nallib
- María Sánchez‑Ares
- José Manuel Cameselle‑Teijeiro
View Affiliations / Copyright

Affiliations: Department of Medical Oncology, University Hospital Complex of Ourense, Galician Healthcare Service (SERGAS), 32005 Ourense, Spain, Department of Pathology, Clinical University Hospital of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Galician Healthcare Service (SERGAS), 15706 Santiago de Compostela, Spain

Copyright: © Cameselle‑García et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 119
|
Published online on: July 17, 2024

https://doi.org/10.3892/or.2024.8778
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Abstract

Cribriform morular thyroid carcinoma (CMTC) has been included within the group of thyroid tumors of uncertain histogenesis in the recent World Health Organization classification of endocrine tumors. Most CMTCs occur in young euthyroid women with multiple (and bilateral) thyroid nodules in cases associated with familial adenomatous polyposis (FAP) or as single nodules in sporadic cases. CMTC generally behaves indolently, while aggressiveness and mortality are associated with high‑grade CMTC. This tumor histologically displays a distinctive combination of growth patterns with morular structures. Strong diffuse nuclear and cytoplasmic immunostaining for β‑catenin is the hallmark of CMTC. Tumor cells are also positive for thyroid transcription factor‑1 and for estrogen and progesterone receptors, but negative for thyroglobulin and calcitonin. It is possible that the CMTC phenotype could result from blockage in the terminal/follicular differentiation of follicular cells (or their precursor cells) secondary to the permanent activation of the Wnt/β‑catenin pathway. In CMTC, the activation of the Wnt/β‑catenin pathway is the central pathogenetic event, which in FAP‑associated cases results from germline mutations of the APC regulator of WNT signaling pathway (APC) gene, and in sporadic cases from somatic inactivating mutations in the APC, AXIN1 and CTNNB1 genes. Estrogens appear to play a tumor‑promoting role by stimulating both the PI3K/AKT/mTOR and the RAS/RAF/MAPK signaling pathways. Additional somatic mutations (i.e. RET rearrangements, or KRAS, phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α, telomerase reverse transcriptase or tumor protein 53 mutations) may further potentiate the development and progression of CMTC. While hemithyroidectomy would be the treatment of choice for sporadic cases without high‑risk data, total thyroidectomy would be indicated in FAP‑associated cases. There is insufficient clinical data to propose therapies targeting the Wnt/β‑catenin pathway, but multikinase or selective inhibitors could be used in a manner analogous to that of conventional thyroid tumors. It is also unknown whether adjuvant antiestrogenic therapy could be useful in the subgroup of women undergoing surgery with high‑risk CMTC, as well as when there is tumor recurrence and/or metastasis.

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Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review)

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