A 30-year-old man presents with secondary hypertension. 24-hour urine catecholamines are markedly elevated. CT shows a 4 cm right adrenal mass. Germline testing reveals a SDHB mutation. Which is the most important clinical implication of SDHB mutation in this context compared with a sporadic pheochromocytoma?

• A SDHB mutations indicate a higher risk of bilateral pheochromocytoma without increased malignant potential
• B SDHB-mutated pheochromocytomas/paragangliomas have a markedly higher risk of malignancy (25–70%) compared to sporadic tumors (<10%), and warrant long-term surveillance due to distant metastasis potential to bone, liver, and lung ✓
• C SDHB mutation predicts excellent response to MIBG therapy due to uniform MIBG-avidity
• D SDHB mutation confers resistance to surgical excision and requires neoadjuvant chemotherapy before resection

Explanation

SDHx-related pheochromocytomas/paragangliomas (PPGL) carry the highest malignant risk among the hereditary forms. Specifically, SDHB mutations are associated with a 25–70% risk of malignant PPGL (defined by distant metastasis), compared to <10% for sporadic cases and lower rates for SDHA, SDHC, SDHD, and SDHE mutations. SDHB-mutated PPGLs are often extra-adrenal paragangliomas, show norepinephrine/dopamine secretion, and tend to be MIBG-negative (low MIBG avidity), necessitating FDG-PET and somatostatin receptor imaging for staging. Lifelong surveillance (annual biochemical + imaging) is recommended even after resection due to recurrence risk. Bilateral pheochromocytomas are most characteristic of VHL, MEN2, and NF1 mutations.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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