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.

Keywords: Adrenal; Composite tumours; Ganglioneuroblastoma; Ganglioneuroma; Incidentaloma; Neuroblastoma; Phaeochromocytoma; Schwannoma.

Fig. 1

Low power view (×4) showing pheochromocytoma (solid black arrow) and ganglioneuroma (solid white arrow) as part of the composite phaeochromocytoma. The inset shows chromogranin A staining at ×10 magnification

Fig. 2

Low power view (×4) with background adrenal (solid black arrow) in the left upper part of the picture and composite pheochromocytoma on the right. The inset is a high-power view (×10) showing pheochromocytoma on the left (solid black arrow) and ganglioneuroma on the right (solid white arrow)

Fig. 3

Low power view (4x) showing S100 staining highlighting the Schwann cells and the sustentacular cells of the composite pheochromocytoma (solid black arrows) but sparing the ganglion cells (solid white arrow) of the ganglioneuroma

Fig. 4

Modified PRISMA flow diagram showing the process of inclusion and exclusion of articles included in this review

Fig. 5

Pie chart showing patients with composite phaeochromocytoma in the review stratified by underlying genetic syndrome

Fig. 6

Pie chart showing patients with composite phaeochromocytoma included in the review, stratified by composite tumour components