A pheochromocytoma patient undergoes adrenalectomy. Histology shows large chromaffin cells with granular cytoplasm, arranged in 'Zellballen' (ball-like nests). However, there is NO reliable histological feature that can distinguish benign from malignant pheochromocytoma. The diagnosis of malignancy in pheochromocytoma requires:
- A Nuclear pleomorphism and mitotic rate >2/10 HPF
- B PASS score (Pheochromocytoma of Adrenal gland Scaled Score) >4
- C Capsular or vascular invasion on histology
- D Presence of metastasis at sites where chromaffin cells are not normally present ✓
Explanation
The ONLY definitive criterion for malignancy in pheochromocytoma/paraganglioma is the presence of metastases at sites where chromaffin tissue does not normally exist — such as lymph nodes, liver, lungs, or bone. No histological features (pleomorphism, mitoses, necrosis, vascular invasion) reliably predict malignancy; all pheochromocytomas have malignant potential. The PASS score (>4) and GAPP (Grading system for Adrenal Pheochromocytoma and Paraganglioma) assess risk stratification but not definitive malignancy. SDHx mutations (especially SDHB) confer the highest metastatic risk. WHO 2022 recommends all pheochromocytomas/paragangliomas be considered malignant potential tumors.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.