According to the latest WHO classification, paragangliomas are now classified by type—sympathetic or parasympathetic—and site. The term pheochromocytoma is reserved for adrenal tumors. In addition, malignancy is defined as the presence of metastasis. It is recognized that local invasion may in some cases be lethal, but it does not necessarily indicate metastatic potential. It is still difficult to identify malignant potential in the absence of metastasis.
Interesting new data have been emerging on familial disease, and it now appears that ∼30% of paragangliomas arise in the context of inherited germline mutations in 6 genes: RET, VHL, NF1, SDHB, SDHC, and SDHD. These show some genotype phenotype correlations. Additional genetic changes have also been reported.
In this short review, the general aspects of these tumors are presented, with discussion of the new data on inherited disease and on approaches to defining malignant tumors.
From the Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, UK.
Reprints: Anne Marie McNicol, MD, FRCPath, Department of Pathology, Royal Infirmary, Castle Street, Glasgow, G4 0SF, UK. E-mail: A.M.McNicol@clinmed.gla.ac.uk.