A 40-year-old man with hypertension and hypokalemia is found to have a 2 cm right adrenal adenoma on CT and an elevated aldosterone-to-renin ratio. Which immunohistochemical marker is most useful to distinguish an aldosterone-producing adenoma from cortisol-producing adenoma?

• A SF-1 (steroidogenic factor 1) — expressed in all adrenocortical tumors equally
• B Chromogranin A — distinguishing cortical from medullary adrenal tumors
• C Synaptophysin — marking adrenocortical adenoma over pheochromocytoma
• D CYP11B2 (aldosterone synthase) — expressed in aldosterone-producing adenoma but not cortisol-producing adenoma ✓

Explanation

CYP11B2 (aldosterone synthase) is the rate-limiting enzyme in aldosterone biosynthesis and is selectively expressed in the zona glomerulosa and aldosterone-producing adenomas (APAs). Its IHC expression distinguishes APAs from cortisol-producing adenomas (which express CYP11B1/17β-hydroxylase). CYP11B2 staining is now used in adrenal vein sampling lateralization and to identify multiple aldosterone-producing micronodules. SF-1 marks all adrenocortical cells. Chromogranin and synaptophysin distinguish cortical from medullary (pheochromocytoma), not among cortical adenomas.

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

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Written and medically reviewed by the StethoPrep medical team.