Composite phaeochromocytomas—a systematic review of published literature

Abstract

Introduction Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a single centre’s records and presents a systematic literature review of composite phaeochromocytomas. Methods In addition to describing 2 case reports, a systematic search of the Medline database from inception up to April 2020 was done for human case reports on composite phaeochromocytomas. Relevant titles and/or abstracts were screened, and full texts were reviewed to identify appropriate studies. Data was extracted and a descriptive analysis of presentation, clinical features, management strategies and outcomes was performed. The quality of included studies was assessed using a critical appraisal checklist. Results There were 62 studies included, with a total of 94 patients. Of 91 patients where data was available, the median (range) age of patients was 48 (4–86) years. Of 90 patients where information was provided, 57% were female. In at least 28% of patients, a genetic cause was identified. Common presenting features include abdominal pain, palpable mass, cardiovascular and gastrointestinal symptoms. The most common tumour component with phaeochromocytoma is ganglioneuroma; other components include ganglioneuroblastoma, neuroblastoma and malignant peripheral nerve sheath tumours. In patients with follow-up data (n=48), 85% of patients were alive and well at a median (range) follow-up time of 18 (0.5–168) months. Conclusion Composite phaeochromocytoma is a rare tumour, with a significant genetic predisposition. This review summarises available epidemiological data, which will be useful for clinicians managing this rare condition.

Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations

“…Currently, it is suggested that all patients diagnosed with CP require long-term follow-up, since the clinical course is highly unpredictable. In general, for composite PCC/PGL-GN, the prognosis has been promising based on previous publications, with extreme rare metastasis or death (Table S2) (1,2,8,(23)(24)(25)32,(35)(36)(37)(38)(39)(40)(41)(42)(43). However, careful follow-up is still recommended and predictors for prognosis are waiting to be explored.…”

“…Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm consisting of pheochromocytoma (PCC) or paraganglioma (PGL) combined with developmentally related neurogenic tumor (1). Its neurogenic component is various, including ganglioneuroma (GN), neuroblastoma, ganglioneuroblastoma, etc (1,2). Currently, little is known about its pathogenesis and relationship with its pure tumor counterparts.…”

Adrenal Ganglioneuroma: A Case Report

“…Ganglioneuroma is a benign tumor arising from the neural crest, Schwannien stroma, and connective tissue of the sympathetic channel. It mainly occurs in the posterior mediastinum or retroperitoneum, but also in the adrenal glands and the neck [ 1 , 2 ]. AGN is rare, representing 21% of all GNs [ 3 ].…”

Adrenal ganglioneuroma: Prognostic factors (Review)

“…At the end of the aggressive spectrum, there is neuroblastoma, while at the other end exhibiting generally considered benign features there is ganglioneuroma (3). Adrenal medulla is also the origin of pheochromocytomas with different grades of differentiation and associated malignant potential and also composite pheochromocytoma, a distinct rare entity (4,5).…”

“…Ganglioneuroma, a benign tumor of neuroblastic type, originates from the autonomous sympathetic nervous system, either central or peripheral; thus, the sites can be anywhere in relationship to the presence of autonomic ganglia such as the adrenals, retroperitoneum, mediastinum/thorax, and cervical area (4,5). Ganglioneuroma is considered to be a tumor with the least aggressive profile among all neuroblastic tumors since it exclusively has mature cells; it is also the rarest tumor of this category (6).…”