Answer: Paraganglioma

Histology: This tumor has a predominantly nested to alveolar pattern. It has a highly vascular stroma that is hyalinized. The tumor cells have, for the most part, fairly uniform, “salt and pepper” type chromatin in a background of purplish, granular, “amphophilic” cytoplasm. Focally, however, there are areas of extreme cytologic atypism. Tumor cells were immunoreactive for synaptophysin and chromogranin, and negative for cytokeratin. S100 immunostain demonstrated labeling in a sustentacular pattern.

Discussion: A neuroblastoma would feature a similar nested growth pattern and highly vascularized stroma. However, neuroblastoma is characterized by primitive neuroblasts without well-defined cytoplasm and often demonstrates differentiation into ganglion cells in a background of neuropil. Neuroblastoma would be far less common in the adult age group. Neuroendocrine carcinoma might also have a nested growth pattern, but it typically lacks the amphophilic cytoplasm seen in a paraganglioma. Neuroendocrine carcinoma would label for cytokeratin and typically lacks an S100-positive sustentacular cell population. Melanoma would be immunoreactive for S100 protein and HMB 45, and would not label for chromogranin and synaptophysin. Melanoma characteristically has prominent nucleoli, which were not seen in the current case.

Only the presence of metastasis proves that a pheochromocytoma or its extra-adrenal counterpart, paraganglioma, is malignant. However, extra-adrenal location, coarse nodularity, confluent tumor necrosis, and the absence of hyaline cytoplasmic vacuoles have been correlated with increased chance of malignancy. Specifically, approximately 30-50% of extra-adrenal abdominal paragangliomas prove to be malignant, whereas only about 10% of adrenal pheochromocytomas prove to be malignant. Extra-adrenal paraganglioma has been associated with the Carney complex (gastric epithelioid leiomyosarcoma, pulmonary chondroma, extra-adrenal paraganglioma).