Answer: Pheochromocytoma

Histology: The tumor is well circumscribed and consists of basophilic polygonal cells with pleomorphic nuclei. Occasional large bizarre cells are seen. Mitotic figures are rare. The cells are arranged in clusters and nests (Zellballen pattern) in a vascular network. Focal areas of hemorrhage and cystic formation are seen.

Discussion: Pheochromocytomas are neoplasms that arise from the adrenal medulla. Clinically, the tumors are associated with marked hypertension due to catecholamine production. Laboratory diagnosis of the tumor is based on detecting free catecholamines and their metabolites, including vanillylmandelic acid (VMA), in urine. The histologic appearance of the tumor along with a clinical history of hypertension and urine laboratory tests is essentially diagnostic of this entity and unlikely to be confused with other tumors.

Adrenal cortical adenomas and carcinomas tend to consist of cells that are clear or eosinophilic. Pheochromocytomas show S100 staining in a sustentacular pattern around the tumor nests and chromogranin within the tumor cells, which are not seen in adrenal cortical lesions. Melanin pigment may be seen in pheochromocytomas. The clinical history and immunohistochemical stains can help to distinguish it from melanoma. While melanoma would be positive for S100, HMB-45, and Melan-A, and negative for chromogranin, pheochromocytomas have the opposite staining pattern. Rarely HMB-45 positive cells may be identified in pheochromocytomas, however, diffuse positivity would argue against the diagnosis.

Pheochromocytomas, as with other neuroendocrine tumors, have the potential to be malignant, however, a diagnosis of malignancy cannot be based on histologic features alone. Features that correlate with aggressive behavior include capsular invasion, vascular invasion, numerous mitoses, and necrosis.