Colon nontumor
Colitis (non-infectious)
Anti-PD1 associated colitis

Author: Maryam Kherad Pezhouh, M.D., M.Sc.
Editorial Board Member Review: Raul S. Gonzalez, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 2 October 2018, last major update August 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Anti-PD1 associated colitis

Cite this page: Pezhouh, M.K. Anti-PD1 associated colitis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colonAntiPD1.html. Accessed October 18th, 2018.
Definition / general
  • Colitis is an immune related adverse event of anti-PD1 (nivolumab, pembrolizumab) and anti-PDL1 medications (atezolizumab, avelumab and durvalumab)
    • PDL1 (programmed death ligand 1) and its receptor PD1 protect host cells from autoreactive T cells; monoclonal antibodies which block this interaction have been approved for treatment of several cancers (see PDL1) topic
Essential features
  • Colitis is an immune-related side effect of anti-PD1 and anti-PDL1 therapy
  • Often mild (diarrhea); very rarely severe (perforation) (Surg Case Rep 2017;3:94)
  • Two main histologic patterns of injury (Am J Surg Pathol 2017;41:643):
    • Active colitis with neutrophilic crypt microabcesses, prominent crypt epithelial cell apoptosis and crypt atrophy / dropout (the most common pattern)
    • Lymphocytic colitis-like pattern with surface injury
    Epidemiology
    Sites
    Pathophysiology
    • Caused by immune dysregulation of the gastrointestinal mucosa
    Clinical features
    • Abdominal pain / cramping, diarrhea
    Radiology description
    • Segmental / diffuse bowel wall thickening, wall contrast enhancement, peritoneal fat infiltration with mesenteric vessel engorgement (Eur J Cancer 2018;96:91)
    Case reports
    Treatment
    • Most patients respond to systemic corticosteroids
    • Tumor necrosis factor α (TNFα) blocking agents such as infliximab can be used in steroid refractory cases
    Clinical images

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    Colonoscopy

    Gross images

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    Small bowel performoration

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    Fig A. Perforation (arrow) Fig B.
    Colonic mucosa with yellowish
    exudate and multifocal ulcers
    Microscopic (histologic) description
    • Most common pattern of injury is focal active colitis
      • Neutrophilic crypt microabcesses with prominent crypt epithelial cell apoptosis
      • Crypt atrophy / dropout
    • Other histopathologic pattern is lymphocytic colitis-like pattern with surface injury
    • Rarely Anti-PD1 associated colitis causes collagenous colitis or perforation
    Microscopic (histologic) images

    Images hosted on PathOut server:

    Contributed by Maryam Kherad Pezhouh, M.D.

    Focal active colitis with crypt drop out

    Prominent crypt epithelial cell apoptosis

    Neutrophilic crypt microabcesses

    Lymphocytic colitis-like pattern

    Negative stains
    Differential diagnosis
    Board review question #1
      A 64 year old man with ulcerative colitis recently completed 3 cycles of pembrolizumab therapy for metastatic carcinoma. He underwent colonoscopy with biopsy for diarrhea. Which feature is key to differentiating anti-PD1 associated colitis from ulcerative colitis?

    1. Increased crypt epithelial apoptosis and lack of significant chronicity
    2. Involvement of the rectum
    3. Presence of crypt abscesses
    4. Presence of erosions
    Board review answer #1
    A. Increased crypt epithelial apoptosis and lack of significant chronicity

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