Endocrine Pathology

, Volume 17, Issue 4, pp 321–328

Molecular and cellular biology of pheochromocytomas and extra-adrenal paragangliomas

EPS Proceedings

DOI: 10.1007/s12022-006-0003-3

Cite this article as:
Tischler, A.S. Endocr Pathol (2006) 17: 321. doi:10.1007/s12022-006-0003-3


Efforts to understand the pathobiology of pheochromocytomas and extra-adrenal paragangliomas have been spurred by genetic and gene expression profiling studies showing genotype-phenotype correlations in familial pheochromocytoma/paraganglioma syndromes and in some sporadic tumors. The current challenge is to relate catalogs of genetic and phenotypic markers to cell biology. Hypothetical bases for genotype-phenotype correlations include: cell of origin, pathway dependence, and functional and anatomic context. A further consideration is phenotype plasticity. Cross talk between signaling pathways provides a general framework for understanding how mutations of apparently unrelated genes might lead to the same type of tumor, and also suggests that targeted therapies might be directed either at a specific mutated gene or a downstream signal transducer. However, precise mechanisms of tumorigenesis remain unknown. An intriguing hypothesis proposes that mutations of RET, NF1, VHL, or SDH predispose to hereditary pheochromocytoma/ paraganglioma by causing defective apoptotic culling of cells that would normally be destroyed during embryogenesis. An argument favoring survival rather than mitogenesis as a common denominator is that the same mutations are rare in sporadic pheochromocytomas/paragangliomas, suggesting they only need to act during a limited developmental window. An implication is that tumor precursors could be identified and eradicated in individuals who carry the mutations.

Key Words

Pheochromocytoma paraganglioma adrenal medulla chromaffin cell paraganglia 

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  1. 1.Department of PathologyTufts New England Medical CenterBoston

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