Colon
Noninfectious colitis
Anti-PD1 associated colitis
Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 1 August 2018
Minor changes: 4 May 2021
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: Anti-PD1 associated colitis
Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Clinical features | Radiology description | Case reports | Treatment | Clinical images | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Negative stains | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Pezhouh M.K. Anti-PD1 associated colitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonAntiPD1.html. Accessed May 17th, 2021.
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
- Incidence of 4 - 19% for patients taking anti-PD1 and anti-PDL1 medication (BMJ 2018;360:k793, Front Pharmacol 2017;8:730)
Sites
- Can affect the entire gastrointestinal tract (Histopathology 2017;70:558) and liver (Mod Pathol 2018;31:965)
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
- 51 year old woman with colonic perforation after treatment with pembrolizumab (anti-PD1 inhibitor) for metastatic melanoma (Case Rep Gastrointest Med 2018;2018:3406437)
- 62 year old man with infliximab refractory severe nivolumab induced enterocolitis (Am J Case Rep 2018;19:360)
- 68 year old woman with anti-PD1 induced collagenous colitis (Melanoma Res 2016;26:308)
- 71 year old man with intestinal perforation after nivolumab immunotherapy for a malignant melanoma (Surg Case Rep 2017;3:94)
- 82 year old man with nivolumab associated colitis mimicking ulcerative colitis (Clin Gastroenterol Hepatol 2017;15:A35)
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
Images hosted on other servers:
Colonoscopy
Gross images
Images hosted on other servers:
Small bowel performoration
Fig A: perforation (arrow)
Fig B: colonic mucosa
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
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
- Other causes of active colitis with prominent apoptosis such as infections (CMV colitis), acute graft versus host disease
- Inflammatory bowel disease: basal plasmacytosis, less apoptosis, evidence of chronicity
- Ipilimumab associated colitis: lymphoplasmacytic expansion of lamina propria, increased apoptosis and intraepithelial lymphocytes, cryptitis and crypt elongation, somewhat similar histology, history probably necessary for distinction
- Idelalisib associated colitis: somewhat similar histology to anti-PD1 associated colitis, history probably necessary for distinction (Am J Surg Pathol 2015;39:1661)
Board review style 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?
- Increased crypt epithelial apoptosis and lack of significant chronicity
- Involvement of the rectum
- Presence of crypt abscesses
- Presence of erosions
Board review style answer #1
A. Increased crypt epithelial apoptosis and lack of significant chronicity
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Reference: Anti-PD1 associated colitis
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