Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term “silent” PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, “clinically silent” is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term “silent” and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.

Bladder Paraganglioma Presenting as Post-Micturition Palpitations: A Case Report

“…PUB is an exceedingly rare entity, accounting for only 1% of all pheochromocytomas and 0.05% of all bladder tumors [ 1 ]. The clinical presentation of PUB can be diverse, and it may mimic other urinary conditions, making it challenging to diagnose.…”

“…Pheochromocytoma is a rare catecholamine-secreting neuroendocrine tumor predominantly arising from chromaffin cells in the adrenal medulla. However, approximately 10% of these tumors can arise from extra-adrenal locations, known as paragangliomas [ 1 , 2 ]. Paraganglioma of the urinary bladder (PUB) is an exceptionally rare extra-adrenal location, accounting for only 0.05% of all bladder tumors and 1% of all pheochromocytomas, with only about 200 cases reported literature [ 3 , 4 ].…”

Imaging of Pheochromocytomas and Paragangliomas

“…Results of plasma or urinary metanephrines are negative in the large majority of HNPGLs and may be false negative in patients with small PPGLs, and in rare cases of nonfunctional PPGLs ( 66 ). In these cases, the diagnosis may primarily rely on PPGL-specific imaging.…”

A biochemically negative phaeochromocytoma

“…5 Despite being biochemically negative, these tumours still carry the risk of catecholamine crisis as they may be functional. 6 Review of published cases revealed perioperative haemodynamic instability in 12 of 13 patients with biochemically negative phaeochromocytomashypertensive crises in six, significant hypotension in eight and Takotsubo cardiomyopathy in one, despite preoperative phenoxybenzamine of variable duration in five patients. 4,8,9 Genetic mutations were found in 12 out of 16 patients tested -SDHB (5), MEN2A (4), VHL (2) and SDHD (1).…”

“…Fewer than 40 biochemically negative phaeochromocytomas have been described. [4][5][6] Characteristic features of phaeochromocytoma on CT include density >10 HU, delayed washout and cystic or haemorrhagic changes. 7 High signal intensity on T2-weighted images on MRI are characteristic of phaeochromocytoma.…”