A Novel, Likely Pathogenic MAX Germline Variant in a Patient With Unilateral Pheochromocytoma.

CONTEXT: Inherited MYC-associated factor X (MAX) gene pathogenic variants (PVs) increase risk for pheochromocytomas (PCCs) and/or paragangliomas (PGLs) in adults and children. There is little clinical experience with such mutations. OBJECTIVE: This report highlights an important approach. METHODS: Clinical assessment, including blood chemistry, imaging studies, and genetic testing were performed. RESULTS: A 38-year-old Hispanic woman was diagnosed with PCC in 2015, treated with adrenalectomy, and referred to endocrinology clinic. Notably, she presented to her primary care physician 3 years earlier complaining of left flank pain, intermittent diaphoresis, and holocranial severe headache. We confirmed severe hypertension (180/100 mm Hg) over multiple antihypertensive regimens. Biochemical and radiological studies workup revealed high plasma metanephrine of 255 pg/mL (normal range, < 65 pg/mL) and plasma normetanephrine of 240 pg/mL (normal range, < 196 pg/mL). A noncontrast computed tomography scan of the abdomen revealed a 4.2 × 4.3 × 4.9-cm, round-shaped and heterogenous contrast enhancement of the left adrenal gland, and a 2-mm nonobstructive left kidney stone. A presumptive diagnosis of secondary hypertension was made. After pharmacological therapy, laparoscopic left adrenalectomy was performed and confirmed the diagnosis of pheochromocytoma. Based on her age, family history, and a high suspicion for genetic etiology, genetic testing was performed that revealed the presence of a novel likely pathogenic variant involving a splice consensus sequence in the MAX gene, designated c0.64-2A > G. CONCLUSION: The phenotype of MAX PV-related disease and paraganglioma are highlighted. The novel c0.64-2A > G mutation is reported here and should be considered in the diagnostic workup of similar cases.

ACROMEGALY AND A GIANT RETROPERITONEAL LIPOSARCOMA PRODUCING IGF-1.

OBJECTIVE: Liposarcoma is the most common histotype of retroperitoneal sarcomas, representing up to 45% of all cases. We report a rare combination of acromegaly and liposarcoma in the same individual. METHODS: Laboratory and imaging studies including an oral glucose tolerance test, measurements of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and a computed tomography scan were performed. RESULTS: The patient was a 60-year-old male with a history of acromegaly diagnosed on the basis of elevated IGF-1 at 1,373 ng/mL (age-appropriate reference range is 87 to 225 ng/mL) and macroadenoma treated with transsphenoidal surgery. He presented 8 years later with a history of abdominal distension and weight loss. Physical examination was notable for a right-sided abdominal mass that was tense and non-fluctuant. Two years earlier, he had a post oral glucose tolerance test GH level <0.25 ng/mL and IGF-1 level of 256 ng/mL (age-appropriate reference range is 55 to 206 ng/mL). Pituitary magnetic resonance imaging reported a 3.7 × 2.0-mm left-sided parasagittal lesion. Computed tomography scan showed a 25.0 × 22.0 × 32.3-cm heterogeneous giant mass in the right abdomen corresponding to a liposarcoma causing displacement of kidney, liver, and bowel loops. The patient was treated with a complete en bloc resection of the liposarcoma with the right kidney (45 × 33 × 17 cm) and tumor (9,400 g). Immunohistochemical examination revealed positive IGF-1 and GH staining. The patient suffered postoperative gastrointestinal bleeding that resulted in hemorrhagic shock and died on the 29th postoperative day after a cardiorespiratory arrest. CONCLUSION: Acromegalic patients are at increased risk of developing various types of neoplasms. This is the first documented coexistence of liposarcoma and history of acromegaly.