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Pathology of Pheochromocytoma and Paraganglioma

  • John Turchini
  • Anthony J. Gill
  • Arthur S. Tischler
Chapter
Part of the Contemporary Endocrinology book series (COE)

Abstract

Pheochromocytomas and paragangliomas are tumors that arise from related neurally-derived cells of the autonomic nervous system. The World Health Organization classification of endocrine tumors arbitrarily reserves the name pheochromocytoma for tumors that arise from the chromaffin cells of the adrenal medulla. Paragangliomas are similar tumors that occur throughout the distribution of sympathetic nerves and ganglia and along branches of the glossopharyngeal and vagus nerves in the head and neck. Pheochromocytomas and paragangliomas may be morphologically and functionally identical or may show functional differences associated with different anatomic sites. Recent molecular and genetic advances have led to greatly increased understanding of these tumors. It is now known that as many as 30% are hereditary. While some of the hereditary disorders, including von Hippel-Lindau syndrome (VHL), MEN2, and neurofibromatosis type 1 (NF1), have been well recognized for decades, recent discoveries have put a new focus on enzymes within the Krebs cycle, especially the succinate dehydrogenase (SDH) genes. Pathogenic germline mutations in the genes encoding subunits of SDH, collectively known as SDHx genes , now account for the largest share of hereditary pheochromocytoma and paraganglioma. Moreover, SDH deficiencies have also been identified in gastrointestinal stromal tumor, renal cell carcinoma, and pituitary adenoma – summarized in Table 2.1. Isocitrate dehydrogenase has also been implicated in a small number of cases. Germline mutations in at least 19 genes have now been identified, and many of these have also been reported to occur as somatic-only mutations in genuinely sporadic tumors. Given the newly recognized importance of heredity, prospective recognition, and accurate pathological diagnosis of pheochromocytoma, paraganglioma, and their syndromically associated tumors is now essential for patient care.

Keywords

Pheochromocytoma Paraganglioma Endocrine tumor Chromaffin cell SDH gene Krebs cycle 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • John Turchini
    • 1
  • Anthony J. Gill
    • 1
  • Arthur S. Tischler
    • 2
  1. 1.University of Sydney and Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore HospitalSt LeonardsAustralia
  2. 2.Department of Pathology and Laboratory MedicineTufts Medical CenterBostonUSA

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