Favier J, Meatchi T, Robidel E, et al. - For carbonic anhydrase 9 (CA9), immunohistochemistry was performed on 207 tumors by the researchers in order to assess whether CA9 immunostaining could be used as a tool to prognosticate the presence or verify the pathogenicity of VHL gene mutations in paraganglioma. A retrospective series of 100 paragangliomas with known mutation status for paraganglioma susceptibility genes was first examined followed by a prospective series of 107 paragangliomas for CA9 immunostaining then by germline and/or somatic genetic testing of all paraganglioma susceptibility genes by next-generation sequencing. Membranous CA9 staining was almost exclusively noted in VHL-related cases. CA9 membranous immunostaining was exhibited by 42 of 48 VHL-mutated samples. Positive cells were either separated, differing from one or two cells to 10–20 cells per tumor block, grouped in areas of focal positivity representing between 1 and 20% of the tissue section, or widely spread on 80–100% of the tumor sections. On the contrary, 142/159 of non-VHL-mutated tumors exhibited no membrane CA9 localization. In conclusion, VHL gene mutations could be prognosticated or verified reliably by an easy-to-perform and low-cost immunohistochemical procedure. Moreover, CA9 immunohistochemistry on paragangliomas would enhance the diagnosis of VHL-related disease, which was significant for the surveillance and therapeutic management of paraganglioma individuals, and in case of germline mutation, their family members.