Answer: Pheochromocytoma

Histology: On microscopic examination, paragangliomas (and thus Pheochromocytomas) show highly vascularized nests and balls of eosinophilic tumor cells. This ball-like appearance has been referred to as a Zellballen appearance. In some cases capillary channels are so prominent that they result in an angiomatous appearance. The proliferating cells are pinkish with abundant granular cytoplasm. Their nuclei are small, uniform and possess small nucleoli. However, as in all endocrine tumors, it is not uncommon to have scattered bizarre-appearing nuclei.

Discussion: Pheochromocytomas are catecholamine-secreting neuroendocrine tumors that develop from chromaffin cells of the sympathetic nervous system. The vast majority occur in any anatomic site, but greater than 90% of these tumors are in the adrenal gland. Approximately 90% of them are benign and 10% are malignant. There are no histologic features, including vascular invasion, that allow separation between benign and malignant theochromocytomas. Approximately 10% of them are syndromic, associated with neurofibromatosis Type I, von Hippel-Lindau disease, and multiple endocrine neoplasia type 2A and 2B. Bilateral examples are more likely in syndromic lesions. A specific scanning technique using MIBG scintigraphy is available to detect these tumors but most patients are discovered by urinary metanephrine levels after presenting with labile hypertension. The sensitivity of MIBG scanning has ranged from about 75% to about 90%. Pheochromocytomas are a part of the family of paragangliomas. A prototype example of paraganglioma (extra-adrenal) is the carotid body tumor which is also called a chemodactoma or sometimes the misnomer glomus jugulare tumor. The normal carotid body serves as a chemoreceptor that seems to have a capacity to assess oxygen tension, carbon dioxide tension, and other functions. As such patients with cystic fibrosis or those living at high altitudes have been shown to have enlarged carotid body paraganglia. If immunohistochemistry is performed the proliferating cells are reactive with antibodies directed against chromogranin and synaptophysin, but they lack epithelial markers. A population of supporting cells named sustentacular cells express S-100 protein and staining for S-100 can highlight these cells and facilitate the diagnosis. The differential diagnosis is with carcinoid tumors, which show epithelial markers, thereby differing from paragangliomas. Other elements in the differential diagnosis include alveolar soft part sarcoma, which differs by lacking sustentacular cells and lacking expression of neuroendocrine markers. Of course, granular cell tumors, which show diffuse expression of S-100 protein. The cytologic features of this lesion are certainly not those of a high grade carcinoma.