Review of Pediatric Pheochromocytoma and Paraganglioma

Abstract

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare chromaffin cell tumors which secrete catecholamines and form part of the family of neuroendocrine tumors. Although a rare cause of secondary hypertension in pediatrics, the presentation of hypertension in these patients is characteristic, and treatment is definitive. The gold standard for diagnosis is via measurement of plasma free metanephrines, with imaging studies performed for localization, identification of metastatic lesions and for surgical resection. Preoperative therapy with alpha-blocking agents, beta blockers, and potentially tyrosine hydroxylase inhibitors aid in a safe pre-, intra- and postoperative course. PCC and PGL are inherited in as much as 80% of pediatric cases, and all patients with mutations should be followed closely given the risk of recurrence and malignancy. While the presentation of chromaffin cell tumors has been well described with multiple endocrine neoplasia, NF1, and Von Hippel–Lindau syndromes, the identification of new gene mutations leading to chromaffin cell tumors at a young age is changing the landscape of how clinicians approach such cases. The paraganglioma–pheochromocytoma syndromes (SDHx) comprise familial gene mutations, of which the SDHB gene mutation carries a high rate of malignancy. Since the inheritance rate of such tumors is higher than previously described, genetic screening is recommended in all patients, and lifelong follow-up for recurrent tumors is a must. A multidisciplinary team approach allows for optimal health-care delivery in such children. This review serves to provide an overview of pediatric PCC and PGL, including updates on the preferred methods of imaging, guidelines on gene testing as well as management of hypertension in such patients.

Paraganglioma: Cytomorphologic features, radiologic and clinical findings in 12 cases

“…Paraganglioma is a neoplasm with a wide age of presentation. Our study demonstrates a range of 16–81 years . FNA is an acceptable and minimally invasive tool to evaluate paragangliomas .…”

“…Paragangliomas are rare neoplasms arising from the sympathetic and parasympathetic autonomic nervous system. They may present as a mass in a variety of locations such as the head and neck, paraspinal, retroperitoneal, and or peripancreatic space as evidenced in the cases included in our series study. Less commonly reported sites included thyroid and both anterior and posterior mediastinum .…”

“…Paraganglioma is found to be a rare cause of secondary hypertension in the pediatric population. While plasma levels of free metanephrines are not essential in diagnosing the tumor, measurement of plasma free metanephrines is gold standard for diagnosing an active paraganglioma as the etiology of hypertension …”

“…In the head and neck, paragangliomas with plasmacytoid cells, spindle cells, single cells, and granular cytoplasm can be misinterpreted as medullary thyroid carcinoma . Moreover, Paragangliomas can mimic acinic cell carcinoma because of their abundant granular cytoplasm, inconspicuous nucleoli, and naked nuclei . Other differential diagnoses include malignant melanoma, oncocytoma, and Hurthle cell carcinoma .…”

“…While plasma levels of free metanephrines are not essential in diagnosing the tumor, measurement of plasma free metanephrines is gold standard for diagnosing an active paraganglioma as the etiology of hypertension. 2 The wide range of morphologic features and distribution of these neoplasms contributes to diagnostic difficulty. In the parapharyngeal space, paragangliomas should be included in the differential diagnosis whenever FNA specimen contains spindle and epithelioid cells.…”