Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Sep 20:7:F1000 Faculty Rev-1500.
doi: 10.12688/f1000research.14568.1. eCollection 2018.

New insights on the pathogenesis of paraganglioma and pheochromocytoma

Vitaly Kantorovich  1 , Karel Pacak  2
Affiliations
Review

New insights on the pathogenesis of paraganglioma and pheochromocytoma

Vitaly Kantorovich et al. F1000Res. .

Abstract

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare chromaffin cell tumors (PPGLs) that at times raise significant challenges in clinical recognition, diagnosis, and therapy and when undiagnosed could associate with severe morbidity. Recent discoveries in PPGL genetics propelled our understanding in the pathophysiology of tumorigenesis and allowed the application of functional classification of pathogenetically distinct groups of PPGLs. This also resulted in a qualitative change in our approach to clinical assessment, diagnosis, and therapy of different subgroups of PPGLs. Establishment of the fact that mutations in multiple components of the PHD-VHL-HIF-2α pathway associate with pseudohypoxia-driven tumorigenesis allowed us not only to better understand the effect of this phenomenon but also to more deeply appreciate the value of functional abnormalities in the physiologic tissue oxygen-sensing mechanism. Mutations in the tricarboxylic acid cycle-related genes opened an additional window into understanding the physiology of one of the basic cellular metabolic pathways and consequences of its disruption. Mutations in the kinase signaling-related genes allow the PPGL field to join a massive innovative process in therapeutic advances in current oncology. New pathophysiologically distinct groups of mutations will widen and deepen our understanding of additional pathways in PPGL tumorigenesis and hopefully introduce additional diagnostic and therapeutic approaches. All of these developments are tremendously important in our understanding of both the normal physiology and pathophysiology of PPGLs and are strong tools and stimuli in the development of modern approaches to all components of medical management.

Keywords: PPGL; Pheochromocytoma; paraganglioma.

PubMed Disclaimer

Conflict of interest statement

No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Differential characteristics of hereditary pheochromocytoma/paraganglioma tumors (PPGLs).
A, degree of PPGL cell differentiation; B, risk of metastatic/malignant potential and norepinephric versus epinephric secretory profile.
See this image and copyright information in PMC

References

    1. Lenders JW, Duh QY, Eisenhofer G, et al. : Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915–42. 10.1210/jc.2014-1498 - DOI - PubMed

    2. F1000 Recommendation

    1. Crona J, Taïeb D, Pacak K: New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification. Endocr Rev. 2017;38(6):489–515. 10.1210/er.2017-00062 - DOI - PMC - PubMed
    1. Dahia PL: Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer. 2014;14(2):108–19. 10.1038/nrc3648 - DOI - PubMed

    2. F1000 Recommendation

    1. Fishbein L, Leshchiner I, Walter V, et al. : Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell. 2017;31(2):181–93. 10.1016/j.ccell.2017.01.001 - DOI - PMC - PubMed

    2. F1000 Recommendation

    1. Favier J, Amar L, Gimenez-Roqueplo AP: Paraganglioma and phaeochromocytoma: From genetics to personalized medicine. Nat Rev Endocrinol. 2015;11(2):101–11. 10.1038/nrendo.2014.188 - DOI - PubMed

    2. F1000 Recommendation

Publication types