Old, New, and Emerging Immunohistochemical Markers in Pheochromocytoma and Paraganglioma

Abstract

The evolution of genetic research over the past two decades has greatly improved the understanding of pheochromocytomas and paragangliomas. It is now accepted that more than one third of pheochromocytoma and paragangliomas arise in the context of syndromic disease, usually hereditary. The genetic profile of these tumors also has important prognostic implications which may help guide treatment. Accompanying the changing molecular landscape is the development of new immunohistochemical markers. Initially used in assisting with diagnosis, immunohistochemical markers have now become an important adjunct to screening programs for inherited conditions and subsequently as prognostic markers. The accessibility and efficiency of immunohistochemistry bring pathologists to the forefront in triaging patients based on tumor genotype-phenotype. In this review, we provide an update on the role of immunohistochemistry in the diagnosis of pheochromocytomas and paragangliomas, as an adjunct to assessment for hereditary disease and finally as a potential tool to assist risk stratification.

Pheochromocytoma-Paraganglioma: Translational Approach from Genetics to Clinical Neuroendocrinology

“…In tumors caused by SDHD germline mutation, the cytoplasm may show a pale and diffuse blush and is different from the granular mitochondrial pattern and should be interpreted as a negative pattern of staining (1). HIF-1α stabilization was associated with SDHx-mutations in HNPGLs, not in PCCs/PGLs.…”

“…Pheochromocytomas and paragangliomas (PPGLs) are rare pathologies and they are mostly benign. According to the World Health Organization classification (2017) of endocrine tumors, pheochromocytomas (PCCs) are tumors of chromaffin cells that arise from the adrenal medulla, whereas paragangliomas (PGLs) are neural crest-derived neuroendocrine tumors that can be found at any level of extra-adrenal paraganglia (from the skull base to the pelvis) (1).…”

An Update on the Histology of Pheochromocytomas: How Does it Relate to Genetics?

“…Some of these genetic variants were considered variants of unknown significance (VUS) [43]. Others have described that many PCC/PGL not associated with MAX mutations also demonstrate loss of MAX expression by immunohistochemistry, and that several PCC/PGL associated with MAX mutations do not demonstrate MAX loss by immunohistochemistry [45]. Therefore, MAX immunohistochemistry needs to be studied in larger series than hitherto performed.…”

“…FH immunohistochemistry using the same criteria as for interpretation of SDHB immunohistochemistry can be used. One group has identified several germline FH-mutated PCC and one somatic FH-mutated PCC with loss of expression of FH by immunohistochemistry [45].…”

Editorial: Special Issue on Immunohistochemical Biomarkers in Endocrine Pathology

“…Ucella, Volante, and Papotti from Italy and Dr. La Rosa from Switzerland review the role of immunohistochemical biomarkers in the diagnostic approach to the classification of neuroendocrine tumors of the gastrointestinal tract, pancreas, lung, and thymus as well as the prognostic and theranostic utility of biomarkers [5]. Dr. Gill and colleagues from Australia discuss the classic as well as new and emerging immunohistochemical biomarkers in pheochromocytoma and paragangliomas [6]. Immunohistochemical markers accompany the evolving molecular landscape of these tumors and have become an adjunct to screening programs for inherited conditions and a tool to assist risk stratification.…”