A 35-year-old man has episodic headaches, sweating, and hypertension with blood pressure reaching 220/130 mmHg during attacks. Plasma free metanephrines are markedly elevated. CT scan shows a 4 cm adrenal mass. The histological hallmark used to distinguish benign from malignant pheochromocytoma is:

• A Presence of sustentacular cells on S100 staining
• B Metastasis to non-chromaffin tissue (lymph nodes, liver, bone) as the only reliable criterion ✓
• C Capsular and vascular invasion confirmed histologically
• D High Ki-67 index (>10%) and atypical mitoses

Explanation

The distinction between benign and malignant pheochromocytoma cannot be reliably made on histological criteria alone — capsular invasion, vascular invasion, necrosis, and high mitotic rate occur in both benign and malignant tumors. The only universally accepted criterion for malignancy is metastasis to sites lacking chromaffin tissue (lymph nodes, liver, lung, bone) — these are sites where pheochromocytoma cells cannot arise de novo, confirming malignant dissemination. The PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) attempts risk stratification but is not definitive for malignancy.

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

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Written and medically reviewed by the StethoPrep medical team.