Colon (tumor & nontumor)
Anti-PD1 associated colitis
Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 August 2018
Revised: 8 January 2019, last major update August 2018
Copyright: (c) 2003-2018, 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 answer #1Cite this page: Pezhouh M.K. Anti-PD1 associated colitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonAntiPD1.html. Accessed August 8th, 2020.
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
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
- 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 answer #1
