RHBDF2 and esophageal squamous cell carcinoma: Tylosis with esophageal cancer (TOC) is a rare, autosomal dominant syndrome associated with late-onset focal nonepidermolytic palmoplantar keratoderma, germline mutations in RHBDF2 (encoding iRhom2), and a high lifetime risk of ESCC, estimated to be 90% by 70 years.3