Pheochromocytoma and extra-adrenal paraganglioma: updates.

The World Health Organization reserves the term pheochromocytoma for tumors 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. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often adrenergic phenotype, relatively low rate of malignancy, and predilection to occur in particular hereditary syndromes. Malignancy is defined by presence of metastases not local invasion. Occult germline mutations characteristic of familial syndromes are now found in more than 20% of patients with apparently sporadic tumors, bringing the percentage of tumors with a known genetic basis close to 30%. In addition, tumor location and risk of malignancy vary with the underlying genetic defect. The "10 percent rule" for pheochromocytoma/paraganglioma--10% familial, 10% malignant, 10% extra-adrenal--is therefore no longer tenable. Current roles of pathology are limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy.