A 30-year-old woman with episodic hypertension, palpitations, and sweating has an adrenal mass. The tumor stains positively for chromogranin A and synaptophysin. Microscopically, cells are arranged in 'Zellballen' (cell balls). Which SDH subunit mutation, when present, specifically indicates hereditary paraganglioma-pheochromocytoma syndrome with risk of malignancy?

• A SDHA mutation
• B SDHB mutation ✓
• C SDHC mutation
• D SDHD mutation

Explanation

SDHB (succinate dehydrogenase subunit B) mutations are associated with the highest risk of malignant paraganglioma/pheochromocytoma and are linked to extra-adrenal paragangliomas. SDHB mutation leads to IHC loss of SDHB staining and is a marker of increased malignant potential compared to SDHD (head and neck paragangliomas, paternal imprinting) or SDHC (mostly benign). All SDH mutations cause HIF-1α accumulation via succinate accumulation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.