CDKN2A and neoplasm: Worrisome immunohistochemical features warranting further molecular assessment include reduced immunoreactivity for SOX10 and/or S100, absence of a CD34-positive lattice-like network, complete loss of p16 expression in tumor cells, complete H3K27me3 loss, increased p53 immunoreactivity (or a null cell pattern), and increased Ki-67 labeling index (Figure 2).39,53–60 However, in cases with limited tissue, molecular analysis can be prioritized over immunohistochemistry.