Early-Onset Sarcoma With Germline MAX Variant: Expanding the Spectrum in Hereditary Pheochromocytoma and Paraganglioma

Germline pathogenic variants in MYC-associated factor X (<i>MAX</i>) are a rare cause of hereditary pheochromocytoma and paraganglioma (PPGL) syndrome, typically presenting with pheochromocytomas (PCC). Although <i>MAX</i>-related PPGLs are generally characterized by an adrenergic phenotype and bilateral tumors in 67% of cases, the tumor spectrum associated with <i>MAX</i> pathogenic variants remains poorly understood. We present a case of a 28-year-old man with a germline <i>MAX</i> pathogenic variant (c.64-2A>G) who developed bilateral PCC and later, a liver sarcoma with a <i>TP53</i> variant and <i>PLEKHO2::BRAF</i> gene fusion. The diagnosis of sarcoma in this young patient underscores a potential association between <i>MAX</i> pathogenic variants and an increased predisposition to sarcoma development. Our findings suggest that <i>MAX</i>-related PPGLs may be associated with other malignancies, including sarcoma, and support expanding surveillance guidelines to include whole-body imaging for early detection of extra-adrenal tumors. Given the rarity of <i>MAX</i> pathogenic variants, further studies are needed to elucidate the full spectrum of presentation and establish comprehensive evidence-based surveillance strategies.