Interestingly, CYLD-wildtype carcinomas with cylindroma-like basement membrane inclusions showed strikingly similar genomics to CYLD-mutant cases, with similarly low TMB and significantly less frequent alterations in PIK3CA, KMT2D, and FBXW7. Furthermore, these cases were enriched for inactivating alterations in NF-kappa-B inhibitor alpha (NFKBIA), leading us to consider that cylindroma-like features in HNSCC may be associated with non-CYLD mutations that activate related pathways. The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.