Familial adenomatous polyposis-associated, cribriform morular variant of papillary thyroid carcinoma harboring a K-RAS mutation: Case presentation and review of molecular mechanisms

摘要

The cribriform morular variant of papillary thyroid carcinoma (CMVPTC) is a rare subtype of papillary thyroid cancer that occurs most often in association with the familial adenomatous polyposis (FAP) syndrome. Patient findings: A 18-year-old woman presented with recurrence of PTC in her neck. She had a prior diagnosis of FAP syndrome. Review of her original pathology slides reclassified the case as a CMVPTC. The tumor was examined for the four most common mutations found in PTC: BRAF, RET/PTC, RAS, and PAX/PPARγ. Summary: The molecular alterations associated with CMVPTC involve the WNT signaling pathway but are incompletely understood. When CMVPTC is associated with the FAP syndrome, a germline adenomatous polyposis coli (APC) gene mutation is almost always detected. For the initiation of oncogenesis however, one or more additional molecular alterations must occur, such as a new somatic mutation in the APC gene (biallelic inactivation), somatic mutations in the β-catenin (CTNNB1) gene, or gene-gene interaction (epistasis). To date, of the mutations commonly associated with PTC, only RET/PTC mutations have been reported in CMVPTC. We report a FAP-associated CMVPTC tumor with atypically aggressive features harboring a RAS mutation and review the molecular mechanisms associated with this interesting PTC subtype. The literature was reviewed using MEDLINE (included case presentations, original research, and reviews). Conclusion: We report here the first RAS mutation detected in an FAP-associated CMVPTC tumor.