Pheochromocytoma and paraganglioma: from epidemiology to clinical findings

Abstract

P heochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, and PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system. [1, 2] Paragangliomas originate from sympathetic or parasympathetic ganglia in the abdomen, thorax, and pelvis. Paragangliomas may also originate from parasympathetic ganglia at the base of the skull and along the glossopharyngeal nerve and vagus nerve in the neck. [2] The majority of PCCs and sympathetic PGLs are endocrine active tumors, and they cause clinical symptoms by secreting excess catecholamines (norepinephrine, epinephrine, Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, and PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system. Paragangliomas originate from sympathetic or parasympathetic ganglia in the abdomen, thorax, and pelvis. The majority of PCC and sympathetic 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 prevalence between 1:2500 and 1:6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatric patients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between 2-4.5% 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 the remaining sporadic patients, at least 1/3 has a somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditary cases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. Although PCCs and PGLs have scoring systems for histological evaluation of the primary tumor, it is not possible to diagnose whether the tumor is malignant since there is no histological system approved for the biological aggressiveness of this tumor group. Metastasis is defined as the presence of chromaffin tissue in non-chromaffin organs, such as lymph nodes, liver, lungs and bone. Although most 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 predict the prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.

Pheochromocytoma of the organ of Zuckerkandl

“…Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors originating from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia [7] . These tumors arise within the adrenal glands in approximately 85% of cases.…”

‘Case of the month’ from UConn Health, Farmington, CT, USA: management of a giant paraganglioma

“…PGLs are rare neuroendocrine tumours derived from chromaffin cells in the sympathetic or parasympathetic ganglia [1,2]. Like PHEOs, sympathetic PGLs can secrete excess catecholamines resulting in the classical symptoms of episodic hypertension, palpitations, diaphoresis, and headaches.…”

“…Paragangliomas (PGLs) are rare neuroendocrine tumours that are derived from chromaffin cells of the autonomic nervous system. They share a close embryonic origin with phaeochromocytomas (PHEOs), which also arise from chromaffin cells but occur within the adrenal medulla [1]. PGLs can originate in a variety of locations from the neck to the pelvis; however, it is estimated that 70–80% occur within infra‐diaphragmatic sympathetic ganglia such as the organ of Zuckerkandl [2].…”

“…Catecholamine synthesis occurs in the CNS, sympathetic ganglia, and adrenal medulla and is derived from the amino acid tyrosine. The rate‐limiting step is the conversion of l ‐tyrosine to l ‐dihydroxyphenylalanine (DOPA) by the enzyme tyrosine hydroxylase [1]. Thus, medical therapies designed to suppress the symptoms of PPGL are aimed at blocking the production of DOPA and blocking catecholamine‐induced activation of adrenergic receptors.…”

Pheochromocytoma Presenting as Testicular Pain: An Unusual Case Report

“…In 2017, the World Health Organization (WHO) classified PCC as an adrenal tumor and extraadrenal tumor as paraganglioma; since both types of tumor cannot be differentiated on histological findings [1][2][3][4]. e incidence of PCC and paraganglioma ranges between 2 and 8 per million, whereas the incidence of PCC is approximately 500-1600 cases per year [5]. PCC may occur at any age; however, it is more commonly seen in the 3rd to 5th decade of life [3].…”