The protean role of Val804Met RET mutation in thyroid neoplasms: An example of a “MEN2C” syndrome?

Background: Val804Met RET is one of the most common genetic alterations in Multiple Endocrine Neoplasia 2 and is considered to confer only a moderate risk for familial medullary thyroid carcinoma (MTC). The associated phenotype can however be much more complex in some cases. Methods: A clinical, genetic, and pathological analysis was conducted on a family cluster of thyroid neoplasms associated with Val804Met RET mutation. Results: All the kindreds who are carriers of the mutated RET received total thyroidectomy + /- VI level dissection. The proband presented with a pT1bN0 MTC, her 29-yo brother showed a concomitant papillary thyroid carcinoma (PTC) and MTC, their father had a pT1a PTC plus a follicular adenoma, while the uncle of the proband showed C-cell hyperplasia. None had clinical or biochemical evidence of parathyroid disorders or pheochromocytoma. Conclusions: In the presence of Val804Met RET several types of thyroid premalignant and malignant should be screened for, and without limiting to MTC.