Pheochromocytoma : Features of Malignancy

The tumor cells in this pheochromocytoma are arranged in small irregular nests and clusters separated by highly vascular stroma. About 10% of pheochromocytomas are biologically malignant. There are no histologic criteria that can reliably predict outcome. The presence of metastases is the only definitive evidence of malignancy. The most common sites of metastases are bone, lungs, liver, and lymph nodes. Histologic features linked to malignancy include: increased mitotic activity, confluent tumor necrosis, spindle cell morphology, and cellular monotony. Malignancy is more common (20% to 40% of cases) in paragangliomas arising in extra-adrenal locations and in those with germline mutations in one of the linked genes (RET, NF1, VHL, SDHB, SDHC, & SDHD). Malignant lesion are more likely to have elevated dopamine levels and tend to be larger than 5 cm.