Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review).
Oncol Rep
; 52(3)2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39027989
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 highgrade CMTC. This tumor histologically displays a distinctive combination of growth patterns with morular structures. Strong diffuse nuclear and cytoplasmic immunostaining for ßcatenin is the hallmark of CMTC. Tumor cells are also positive for thyroid transcription factor1 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/ßcatenin pathway. In CMTC, the activation of the Wnt/ßcatenin pathway is the central pathogenetic event, which in FAPassociated 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 tumorpromoting role by stimulating both the PI3K/AKT/mTOR and the RAS/RAF/MAPK signaling pathways. Additional somatic mutations (i.e. RET rearrangements, or KRAS, phosphatidylinositol4,5bisphosphate 3kinase 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 highrisk data, total thyroidectomy would be indicated in FAPassociated cases. There is insufficient clinical data to propose therapies targeting the Wnt/ßcatenin 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 highrisk CMTC, as well as when there is tumor recurrence and/or metastasis.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thyroid Neoplasms
Limits:
Female
/
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
Spain