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

Thyroid. 2014 Jul;24(7):1184-9. doi: 10.1089/thy.2013.0589. Epub 2014 May 20.

Abstract

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.

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.

Publication types

  • Case Reports

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / pathology*
  • Adolescent
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology*
  • Female
  • Germ-Line Mutation
  • Humans
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • beta Catenin / genetics
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • beta Catenin
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins