GPNMB and Cowden syndrome 1: Although GPNMB immunohistochemistry detects giant cells in both CS and GCM, the spatial organization of HLA-DRhi macrophages offers a means of diagnostic distinction: in CS, GPNMB+ giant cells are closely encircled by HLA-DRhi macrophages, whereas in GCM, these cell populations are more diffusely distributed throughout lesions.