Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings

Özet

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffincells in the adrenal medulla, and PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system. Paragangliomasoriginate from sympathetic or parasympathetic ganglia in the abdomen, thorax, and pelvis. The majority of PCC andsympathetic PGL are endocrine active tumors causing clinical symptoms by secreting excess catecholamines (norepinephrine,epinephrine, dopamine) and their metabolites. The incidence of PCC and PGL ranges between 2 and 8 per million, with a prevalencebetween 1:2500 and 1:6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatricpatients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between2-4.5% in the pediatric age group. 10-49% of these tumors is detected incidentally in imaging techniques performed for other reasons.However, 4-8% of adrenal incidentalomas are PCCs. Of these neuroendocrine tumors, 80-85% are PCCs and 15-20% are PGLs.Up to 40% of patients with PCC and PGL has disease-specific germline mutations and the situation is hereditary. Of 60% of theremaining sporadic patients, at least 1/3 has a somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditarycases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. AlthoughPCCs and PGLs have scoring systems for histological evaluation of the primary tumor, it is not possible to diagnose whether thetumor is malignant since there is no histological system approved for the biological aggressiveness of this tumor group. Metastasisis defined as the presence of chromaffin tissue in non-chromaffin organs, such as lymph nodes, liver, lungs and bone. Althoughmost of the PCC and PGL are benign, the metastatic disease may develop in 15-17%. Metastatic disease is reported between 2-25%in PCCs and 2.4-60% in PGLs. The TNM staging system of the American Joint Committee on Cancer (AJCC) was developed to predictthe prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.Keywords: Catecholamine synthesis and metabolism; paraganglioma; pheochromocytoma.