COMPOSITE PHEOCHROMOCYTOMA (WITH ASSOCIATED GANGLIONEUROMA) AS A CAUSE OF SECONDARY ENDOCRINOLOGICAL HYPERTENSION

Abstract

Objective: To illustrate and understand a rare variant of pheochromocytoma, its clinical implications and prognosis, based on a clinical case of secondary hypertension. Design and method: Review of the patient's clinical record and the relevant literature. Results: Composite paraganglioma or pheochromocytoma is a rare tumour (<100 reported cases) composed of paraganglioma or pheochromocytoma plus another neurogenic tumour, most often (∼75%) ganglioneuroma, a typically benign tumour derived from the sympathogonia of the neural crest. It can be associated with neurofibromatosis type I, von Hippel-Lindau disease, or MEN2. Our patient is a 64-year-old woman with uncontrolled hypertension, without a history of hypertensive crises. During follow-up for breast adenocarcinoma, a CT scan revealed bilateral adrenal nodules consistent with metastases. PET-CT showed increased metabolic uptake suggesting malignancy in the right adrenal. Plasma metanephrines were very high and MIBG scintigraphy was consistent with a right pheochromocytoma. Following doxazosin blockade, robotic adrenalectomy was performed, and a month later plasma metanephrines and blood pressure were normal. Pathology revealed a single mass of 4x3x2 cm labelled as composite pheochromocytoma (30%) - ganglioneuroma (705). There was no vascular invasion or necrosis, S-100 staining was preserved, and mitotic activity was minimal. In addition to the PASS scale for prognosis of malignancy in pheochromocytoma, there is a specific COPPS scale for composite pheochromocytoma, based on necrosis, loss of S100, loss of SDHB, vascular invasion, and size >7 cm (5/2/1/1/1 points, respectively), with low risk if <3; our patient scores 0-1 (pending SDHB). The patient continues oncological follow-up for breast pathology, but her secondary hypertension is clinically resolved and the risk of pheochromocytoma-ganglioneuroma metastases is apparently low. There are no clinical signs of neurofibromatosis type 1, von Hippel-Lindau, or MEN2. Conclusions: Composite pheochromocytoma is a rare cause of secondary hypertension, often indistinguishable clinically from simple pheochromocytoma, except occasionally due to the larger lesion size. Diagnosis is typically confirmed through histopathological examination. In the most common association (with ganglioneuroma), additional malignancy implications are rare, unlike with other neurogenic tumours such as neuroblastoma or ganglioneuroblastoma. Due to insufficient current knowledge of its natural history, close monitoring is required.