Medullary thyroid carcinoma (MTC) arises from parafollicular C cells. Which genetic mutation, when found on somatic testing of an apparently sporadic MTC, should trigger germline RET testing of the patient and family?

• A BRAF V600E mutation in the tumour
• B RET M918T somatic mutation (found in ~50% of sporadic MTC) ✓
• C RAS mutations (HRAS, KRAS, NRAS) in the tumour
• D TP53 somatic mutation

Explanation

Approximately 25% of all MTC cases are hereditary (MEN2A, MEN2B, or familial non-MEN MTC) due to germline RET mutations. Even when MTC appears sporadic, somatic RET mutations are found in ~50%. The current recommendation (ATA 2015 guidelines) is that ALL patients diagnosed with MTC should undergo germline RET testing regardless of family history, as de novo mutations occur. A somatic RET M918T mutation (exon 16) in the tumour is the most common mutation and correlates with the highest aggressiveness (MEN2B phenotype).

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.