Medullary thyroid carcinoma with pheochromocytoma and cystic parathyroid degeneration in a ret-negative patient: a case report.

Introduction: 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