<s>[INST] context: Pheochromocytoma are neoplasms composed of chromaffin cells, which synthesize and release catecholamines and in some instances peptide hormones. It is important to recognize these tumors because they are a rare cause of surgically correctable hypertension. Pheochromocytoma range from small, circumscribed lesions confined to the adrenal to large hemorrhagic masses weighing kilograms. The tumors are composed of polygonal to spindle-shaped chromaffin cells or chief cells, clustered with the sustentacular cells into small nests or alveoli (zellballen) by a rich vascular network. The cytoplasm has a finely granular appearance, best demonstrated with silver stains, due to the presence of granules containing catecholamines. The nuclei are usually round to ovoid, with a stippled “salt and pepper” chromatin that is characteristic of neuroendocrine tumors.
There is no histologic feature that reliably predicts clinical behavior. Several histologic features, such as numbers of mitoses, confluent tumor necrosis, and spindle cell morphology, have been associated with an aggressive behavior and increased risk of metastasis, but these are not entirely reliable. Tumors with “benign” histologic features may metastasize, while bizarrely pleomorphic tumors may remain confined to the adrenal gland. In fact, cellular and nuclear pleomorphism, including the presence of giant cells, and mitotic figures are often seen in benign pheochromocytomas, while cellular monotony is paradoxically associated with an aggressive behavior. Even capsular and vascular invasion may be encountered in benign lesions. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone. [/INST] question: The definite diagnosis of malignancy in pheochromocytoma is based on | options: A: Presence of metastasis B: Cellular pleomorphism C: Nuclear pleomorphism D: Mitotic figures | answer: A </s>