家族性GH-PitNETと生殖細胞系列MAX変異の関連を示す組織学的証拠

MAX is a tumor suppressor gene, with germline pathogenic variants predisposing primarily to pheochromocytomas and, uncertainly to pituitary neuroendocrine tumor (PitNET). We report the first molecularly confirmed case of a MAX-related growth hormone (GH)-PitNET. A 20-year-old woman presented with acute hemiparesis, hemianopsia, and recent acromegaloid changes. MRI showed a giant invasive PitNET with brainstem compression. Biochemical testing confirmed acromegaly. Despite multimodal therapy (lanreotide, cabergoline, two debulking surgeries), disease control was achieved only after pasireotide and adjuvant proton therapy. Histology confirmed a sparsely granulated somatotroph adenoma. Germline analysis identified a heterozygous MAX pathogenic variant c.97C>T, introducing a premature stop codon (p.Arg33Ter). Tumor analysis found loss of heterozygosity and absence of MAX protein expression. The same variant was found in her father, who had a smaller intrasellar macroadenoma causing acromegaly. This familial observation provides the functional evidence that MAX is a driver in GH-PitNET and a candidate gene for PitNET predisposition.