Pathology of pheochromocytoma and extra-adrenal paraganglioma

The 2004 WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. While arbitrary, this nomenclature serves to emphasize important distinctive properties of intra-adrenal tumors that must be taken into account in clinical practice and research. Those include an often adrenergic phenotype, a relatively low rate of malignancy, and a predilection to occur in particular hereditary syndromes. Current roles of pathology are limited to distinguishing primary or metastatic pheochromocytomas/paragangliomas from other endocrine or nonendocrine tumors, and flagging tumors that show features suggestive of malignant potential or syndromic disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy. Pathology practice currently rests mostly on interpretation of conventional histological sections stained with hematoxylin and eosin, with variable ancillary application of immunohistochemical staining. Malignancy is currently defined by the presence of metastases, not local invasion. Local invasion alone is a poor predictor of metastases, and the absence of apparent invasion does not preclude development of metastases. The two types of aggressive behavior might therefore have different biological underpinnings, and those will be resolved most effectively if consistent terminology is employed. In order to be optimally informative, pathology reports must employ consistent nomenclature and incorporate standard elements. Templates or checklists for minimal standard reporting are recommended by several pathology associations, but identification of some recommended and optional elements is currently subjective or inconsistent.