Hereditary predispositions are responsible for more than 30% of or paraganglioma. Their identification is essential to optimize medical care and to offer an appropriate screening to relatives. To date, there are more than 15 known paraganglioma/pheochromocytoma predisposing genes. The most frequently involved are those encoding the succinate dehydrogenase (SDHx), accounting for half of cases and the VHL gene, causing the Von Hippel Lindau syndrome and representing approximately 20% of genetically determined cases. Patients with SDHB genes mutations have a higher risk of metastatic disease. An oncogenetic counseling is recommended to all patients developing one or several paragangliomas, isolated or associated with other tumors. Apart from the clinical presentation and in particular the syndromic forms characterized by specific tumor spectra, there is no validated morphological criterion allowing to suspect a hereditary form. On the other hand, pathologists have now access to several immunohistochemical tools allowing the identification of some hereditary forms, in particular those linked to the SDHx, VHL and FH genes. Thus, the loss of expression in immunohistochemistry of the SDHB or FH proteins orientates respectively, towards SDHx and FH genes, while the membrane expression of carbonic anhydrase IX (CA-IX) is a sensitive and specific tool pointing towards a VHL anomaly. Other immunohistochemical markers are under evaluation. A systematic SDHB immunohistochemical staining is recommended on all paragangliomas/pheochromocytomas in order to allow an early detection of the most common hereditary forms and to contribute to the interpretation of the genetic results in these patients seen in oncogenetics consultation.
Keywords: CA-IX; FH; FH.; Hereditary paraganglioma/pheochromocytoma syndrome; Immunohistochemistry; Immunohistochimie; SDHB; Syndrome des paragangliomes/phéochromocytomes héréditaire; VHL.
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