Pheochromocytoma and multicentric giant cell tumor of bone

Pheochromocytomasand paragangliomas (PPGLs) are rare catecholamine-secreting tumors that can affect systemic physiology, including bone metabolism. Although they are typically associated with genetic syndromes such as MEN2 and von Hippel-Lindau disease, PPGLs are not commonly linked to primary bone tumors. However, recent findings suggest a novel cancer syndrome involving both PPGLs and giant cell tumor of bone (GCTB) through H3F3A mutations. We report a rare case of a 53-year-old woman with multicentric GCTB, initially diagnosed at age 24, who subsequently developed bilateral pheochromocytomas. Following multiple recurrences of skeletal tumors and eventual leg amputation, imaging and biochemical evaluation revealed bilateral adrenal tumors with markedly elevated catecholamine levels. Genetic analysis identified mosaicism for a pathogenic H3F3A (G35W) variant in both adrenal and bone tumors. Surgical resection of both adrenal glands normalized catecholamine levels and resolved hypertension. The patient has remained tumor-free and normotensive for five years following adrenalectomy. This case supports the existence of a shared pathogenic mechanism linking PPGLs and GCTBs, likely mediated by postzygotic H3F3A mutations. Recognition of this association is crucial for early diagnosis, genetic counseling, and management of similar cases.