Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases

Abstract

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

Adrenal Ganglioneuroma: Diagnosis, Presentation, and Management of a Rare Tumor

“…However, failure to identify these masses can lead to life-threatening complications during surgery [ 12 ], highlighting the need for vigilant pre- and intraoperative blood pressure surveillance even in the setting of normal metanephrine levels. It is worth noting that Araujo et al [ 13 ] (2022) reported three cases of composite pheochromocytoma-ganglioneuroma, which is a rare variant of adrenal ganglioneuroma characterized by the coexistence of a pheochromocytoma and a ganglioneuroma within the same tumor. Patients with composite pheochromocytoma-ganglioneuroma may present with symptoms related to excess catecholamine secretion, similar to those with pheochromocytomas [ 13 ].…”

“…It is worth noting that Araujo et al [ 13 ] (2022) reported three cases of composite pheochromocytoma-ganglioneuroma, which is a rare variant of adrenal ganglioneuroma characterized by the coexistence of a pheochromocytoma and a ganglioneuroma within the same tumor. Patients with composite pheochromocytoma-ganglioneuroma may present with symptoms related to excess catecholamine secretion, similar to those with pheochromocytomas [ 13 ]. In this case, since there were no histological findings of a pheochromocytoma, including no excess catecholamine secretion, positive staining for chromogranin A, or dopamine beta-hydroxylase, the presence of a composite pheochromocytoma-ganglioneuroma was effectively ruled out.…”