Eren Aysegul, Brock Pamela L, Dedhia Priya H
Division of Endocrinology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center and Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Division of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center and Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
JCEM Case Rep. 2025 Jun 9;3(7):luaf119. doi: 10.1210/jcemcr/luaf119. eCollection 2025 Jul.
Germline pathogenic variants in MYC-associated factor X () are a rare cause of hereditary pheochromocytoma and paraganglioma (PPGL) syndrome, typically presenting with pheochromocytomas (PCC). Although -related PPGLs are generally characterized by an adrenergic phenotype and bilateral tumors in 67% of cases, the tumor spectrum associated with pathogenic variants remains poorly understood. We present a case of a 28-year-old man with a germline pathogenic variant (c.64-2A>G) who developed bilateral PCC and later, a liver sarcoma with a variant and gene fusion. The diagnosis of sarcoma in this young patient underscores a potential association between pathogenic variants and an increased predisposition to sarcoma development. Our findings suggest that -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 pathogenic variants, further studies are needed to elucidate the full spectrum of presentation and establish comprehensive evidence-based surveillance strategies.
MYC相关因子X（MAX）的种系致病性变异是遗传性嗜铬细胞瘤和副神经节瘤（PPGL）综合征的罕见病因，通常表现为嗜铬细胞瘤（PCC）。虽然与MAX相关的PPGL通常具有肾上腺素能表型，67%的病例为双侧肿瘤，但与MAX致病性变异相关的肿瘤谱仍知之甚少。我们报告一例28岁男性，其携带种系MAX致病性变异（c.64-2A>G），先后发生双侧PCC，随后发生伴有MAX变异和基因融合的肝肉瘤。该年轻患者肉瘤的诊断突出了MAX致病性变异与肉瘤发生易感性增加之间的潜在关联。我们的研究结果表明，与MAX相关的PPGL可能与包括肉瘤在内的其他恶性肿瘤有关，并支持扩大监测指南，以包括全身成像，以便早期发现肾上腺外肿瘤。鉴于MAX致病性变异的罕见性，需要进一步研究以阐明其完整的临床表现谱，并建立基于证据的全面监测策略。
