Medullary thyroid carcinoma with pheochromocytoma and cystic parathyroid degeneration in a ret-negative patient: a case report
Ahmad El Khatib, Zeina Maria Semaan, Mohamad El Haress, Elie Nehme, Nada Assaf, Monzer Saleh, Nina Shabb, Jad Chokr, Anthony Shebly, Hind Salloum, Mustapha El LakisIntroduction:
Multiple endocrine neoplasia type 2A (MEN2A) is a rare autosomal dominant hereditary cancer syndrome, predominantly caused by mutations of the
Case presentation:
We report the case of a 63-year-old female who was diagnosed with MTC and pheochromocytoma. and cystic parathyroid gland. Genetic workup was negative for
Case discussion:
MEN2A is associated with pathogenic germline variants in the RET proto-oncogene in approximately 95–99% of cases. Our patient, however, exhibited a MEN2A-like clinical phenotype in the absence of an identifiable RET mutation, with a pathogenic TMEM127 variant instead. Although TMEM127 is an established susceptibility gene for pheochromocytoma and paraganglioma, its association with the broader MEN2A phenotype remains unclear. This unusual genotype–phenotype discordance raises important questions regarding the potential role of alternative genetic pathways in MEN2-like syndromes and creates uncertainty regarding postoperative surveillance and the appropriate extent of screening and genetic counseling for family members
Conclusion:
Our case represents an unusual scenario where the patient presents with a clinical phenotype of MEN2A but is