title: Squamous cell dysplasia in the proximal rectum of three patients treated for ulcerative colitis on immunomodulators.
abstract: BACKGROUND
  Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL.
  
  
  OBJECTIVE
  We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL.
  
  
  RESULTS
  Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas.
  
  
  CONCLUSIONS
  This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.
authors.affiliation: Department of Medical Education, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 13th Floor, New York, NY, 10029, USA. james.connolly@icahn.mssm.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Connolly
authors.affiliation: Department of Medical Education, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 13th Floor, New York, NY, 10029, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Goldstone
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000473:pathology*; D012007:Rectum / Q000473:pathology*
chemical_list: D007155:Immunologic Factors
keywords: 6-MP; HPV; HSIL; Immunomodulators; Squamous cell dysplasia; Ulcerative colitis