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


METHODS
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.


CONCLUSIONS
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).


CONCLUSIONS
We report here the first RAS mutation detected in an FAP-associated CMVPTC tumor.
1 Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center and the David Geffen School of Medicine at UCLA , Torrance, California.
Silvana M
SM
Giannelli
Laron
L
McPhaul
Jon
J
Nakamoto
Andrew G
AG
Gianoukakis
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000473:pathology*; D000293:Adolescent; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins