ESMO guidelines for immunotherapy recently recommended the use of MMR immunohistochemistry as the primary method for MSI testing in any cancer belonging to the LS spectrum (colorectal, endometrial, small intestine, urothelial, gliomas/glioblastomas, and sebaceous gland) and to move to MSI-PCR whenever the IHC interpretation is doubtful and as a confirmatory test in case of isolated loss of PMS2 or MSH637,38. This evidence concerns the gene PMS2 and central nervous system cancer.