Histological evidence of familial GH-PitNET associated with germline MAX mutation

Dear Editor, The MAX gene encodes for MAX (MYC-associated factor X), a transcription regulator, which complexes with MYC, an oncoprotein involved in proliferation, differentiation, and apoptosis. MAX functions as a tumor suppressor gene and is increasingly suspected or demonstrated in the development of multiple tumor types. Germline MAX pathogenic variants have been known since 2011 to predispose to pheochromocytomas (PHEOs).1 MAX has also been described as responsible for the 3PA syndrome, characterized by the association of PHEO, paraganglioma (PPGL), and pituitary neuroendocrine tumor (PitNET) in the same individual or within a family.2-9 More recently, its association with additional endocrine and nonendocrine tumors has supported the emergence of the concept of multiple endocrine neoplasia type 5 (MEN5) for MAX-associated hereditary tumor predisposition syndrome.6,7,10 However, PitNET occurring in families with MAX-related PHEO and PPGL is rare. Of the eleven published cases of MAX-mutated patients with PitNET, none have presented with isolated PitNET without PHEO or PPGL.2-9 Moreover, there is no familial case of PitNet described with a MAX mutation.