Colon
Drug induced colitides
Chemotherapy induced colitis
Editorial Board Member: Danielle Hutchings, M.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Last author update: 22 January 2025
Last staff update: 22 January 2025
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PubMed Search: Chemotherapy induced colitis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2Cite this page: Bomfim I, Saxena R, de Mello ES. Chemotherapy induced colitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonchemoinducedcolitis.html. Accessed August 21st, 2025.
Definition / general
- Mucosal injury of the luminal gastrointestinal tract induced by a variety of chemotherapy drugs (Nat Rev Cancer 2004;4:277)
- This topic excludes related topics discussed separately: anti-PD1 associated colitis, idelalisib associated colitis, ipilimumab associated colitis, mycophenolate mofetil associated colitis, secukinumab induced colitis
Essential features
- ~20% of patients undergoing chemotherapy develop mucositis
- Presenting symptoms include diarrhea, hematochezia and abdominal cramping
- Diagnosis is established by
- Temporal relationship of symptoms to initiation of chemotherapy
- Recognition of specific symptomatic associations with specific drugs (see Clinical features)
Terminology
- Chemotherapy induced colitis
- Chemotherapy induced mucositis (CIM)
ICD coding
Epidemiology
- Incidence in patients receiving standard dose chemotherapy: 40% (Cancer Chemother Pharmacol 2009;64:1)
- Incidence in patients receiving high dose chemotherapy: 100% (Cancer Chemother Pharmacol 2009;64:1)
- Incidence varies with the drug: 40 - 76% (Oxid Med Cell Longev 2022;2022:7255497)
Sites
- Colon
Pathophysiology
- Gastrointestinal tract is highly vulnerable to cytotoxic drugs due to constant proliferative activity in response to regular epithelial shedding at the luminal surface (Cancer 2004;100:2026)
- 5 proposed stages of CIM (Nat Rev Cancer 2004;4:277)
- Initiation: DNA and non-DNA damage to basal epithelial cells and submucosal fibroblasts, with generation of reactive oxygen species (ROS)
- Activation of transduction pathways leading to activation of transcription factors such as p53 and nuclear factor κB (NFκB)
- Signal amplification
- Inflammation with / without ulceration, with / without infection
- Loss of mucosal integrity provides entry points for microorganisms
- May lead to bacteremia and sepsis
- Loss of mucosal integrity provides entry points for microorganisms
- Healing phase
Clinical features
- General symptoms: nausea, vomiting, diarrhea, constipation, abdominal cramping (Cancer Chemother Pharmacol 2009;64:1)
- Secondary symptoms: decreased oral intake, leading to nutritional deficiency, malabsorption, dehydration, increased risk of infection (J Natl Cancer Inst Monogr 2001;2001:31)
- Specific symptomatic associations with specific agents
- 5-fluorouracil (5FU) bolus regimens, irinotecan and fluoropyrimidine combinations associated with diarrhea (Best Pract Res Clin Gastroenterol 2020;48:101691)
- 5FU associated with colonic dysmotility and myelosuppression (World J Gastroenterol 2014;20:3751)
- Paclitaxel associated with ischemic colitis
- May lead to severe complications such as bowel necrosis, colonic perforation or typhlitis (Case Rep Oncol 2017;10:689)
- Clostridioides difficile is associated with paclitaxel chemotherapy, particularly with simultaneous antibiotics (Curr Med Chem 2016;23:4442)
- Neutropenic enterocolitis associated with taxanes, cytosine arabinoside, etoposide (World J Gastroenterol 2017;23:42)
- Ileus associated with vincristine and vinblastine
- Commonly involves the small intestine, although the colon may also be rarely involved (Acta Gastroenterol Belg 2020;83:660)
Diagnosis
- Temporal association of symptoms with initiation of chemotherapy, particularly specific associations listed above
- Computed tomography (CT) imaging or colonoscopy is corroborative but contraindicated in acute cases (Blood Rev 2022;54:100944)
- Biopsy helps to rule out suspected competing causes but is inadvisable in acute cases
Laboratory
- Cannot provide diagnostic confirmation
- Useful to
- Exclude competing causes
- Diagnose neutropenia and thrombocytopenia in cases of neutrophilic enterocolitis (Ann Gastroenterol 2020;33:59)
- Diagnose Clostridioides difficile infection by culture or detection of toxin in blood or stool (Blood Rev 2022;54:100944)
Radiology description
- Bowel wall thickening, mucosal hyperenhancement, dilated bowel loops on CT
- Imaging helpful in the diagnosis of
- Ileus: temporary arrest of intestinal peristalsis resulting in functional blockage of the intestines
- More common in small bowel but may be observed in large bowel as well (Postgrad Med J 1970;46:330)
- Associated with vincristine and vinblastine
- Pneumatosis: increased mucosal permeability to gas due to mucosal disruption or ischemia / infarction (Cancer Imaging 2012;12:163, Abdom Radiol (NY) 2022;47:1298)
- Typhlitis: acute inflammation of the cecum
- Most often seen in patients receiving chemotherapy for leukemia or lymphoma (Abdom Radiol (NY) 2022;47:1298)
- Ileus: temporary arrest of intestinal peristalsis resulting in functional blockage of the intestines
- Endoscopic findings: may show normal mucosa, inflammation or ulceration
Radiology images
Images hosted on other servers:
Marked intestinal distension
Ischemic colitis after gemcitabine and docetaxel
Prognostic factors
- Adverse prognostic factors
- Compromised renal function
- Independent factor for upper and lower gastrointestinal tract mucositis (Cancer 2011;117:648)
- Lower serum albumin
- Associated with drugs metabolized by the liver (doxorubicin, etoposide, cyclophosphamide and bortezomib)
- Associated with drugs with high protein binding (same agents as above + cisplatin) (Cancer 2011;117:648)
- Lower body surface area (BSA)
- Increased risk for lower gastrointestinal toxicity
- Younger age and female sex
- Associated with increased risk of nausea and vomiting; however, alcohol intake > 100 g/day is associated with a reduction in emesis (Best Pract Res Clin Gastroenterol 2020;48:101691)
- Compromised renal function
Case reports
- 22 year old woman affected by breast ductal carcinoma developed neutropenic enterocolitis after chemotherapy combination regimens (docetaxel, adriamycin, cyclophosphamide) (Case Rep Oncol 2020;13:442)
- 48 year old woman with colonic adenocarcinoma was treated after surgery with a chemotherapy based treatment composed of irinotecan, 5-fluorouracil and panitumumab and developed severe colitis (Am J Case Rep 2022;23:e934361)
- 67 year old woman with nasopharyngeal carcinoma developed colitis and colonic perforation after fluorouracil administration (World J Clin Cases 2020;8:1693)
- 78 year old man with hepatocellular carcinoma developed severe colitis with ischemic features after hepatic arterial infusion chemotherapy (HAIC) with cisplatin (Intern Med 2020;59:69)
Treatment
- Dose adjustment or discontinuation (Mod Pathol 2009;22:737)
- Supportive care (e.g., antiperistaltic agents, fluid administration, steroids)
Clinical images
Images hosted on other servers:
Endoscopic features of colitis caused by taxane
Hyperemic mucosa and superficial ulcers
Superficial ulceration and mucous erythema
Gross description
- Most common findings (World J Gastrointest Pathophysiol 2019;10:36)
- Patchy inflammation with superficial ulceration
- Diffuse erythema and loss of vascular pattern
- Patchy inflammation with large, deep ulceration
Gross images
Images hosted on other servers:
Neutrophilic enterocolitis after chemotherapy
Microscopic (histologic) description
- Variable degrees of mixed inflammatory infiltrate in lamina propria, apoptosis particularly at crypt bases, cryptitis, crypt architectural distortion and loss with / without erosions / ulcerations, withered crypts with attenuated epithelium and epithelial atypia (Surg Pathol Clin 2017;10:887)
- Taxanes (mitotic inhibitors: paclitaxel and docetaxel)
- Ring mitoses, increased mitotic figures and apoptosis in the proliferative compartment (Am J Surg Pathol 2008;32:473)
- Epithelial necrosis, ulceration and bowel perforation (Cancer 1989;63:1944, Lancet 2000;355:281)
- Mucosal and submucosal edema, hemorrhage, neutrophils and plasma cells in lamina propria (J Clin Gastroenterol 2001;33:159)
- Irinotecan (topoisomerase inhibitor): apoptosis in surface epithelium and crypt cells (Int J Surg Pathol 2005;13:215)
- 5FU: loss of colonic crypts and goblet cells with crypt disorganization and hypoplasia, acute inflammation, reduced myenteric neurons (Neurogastroenterol Motil 2016;28:1861)
- Hydroxycarbamide: lymphoplasmacytic infiltration, eosinophils, crypt abscesses and erosions (Virchows Arch 2017;470:245)
- Capecitabine (prodrug of 5FU): graft versus host disease (GVHD)-like changes, including crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium and increased crypt apoptosis (Surg Pathol Clin 2017;10:887)
Microscopic (histologic) images
Contributed by Rifat Mannan, M.D. and Danielle Hutchings, M.D.
Numerous ring mitoses
Dilated crypts
Crypt dropout
Increased crypt apoptosis
Increased mitoses with ring mitosis
Negative stains
Molecular / cytogenetics description
- Polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD) can lead to a rate limiting step in fluorouracil catabolism by the enzyme, increasing gastrointestinal toxicity
- Molecular genetic testing for DPYD can assess enzyme activity and risk of toxicity (Medical Genetics Summaries: Capecitabine Therapy and DPYD Genotype [Accessed 10 December 2024])
Sample pathology report
- Colon, biopsy:
- Mild / moderate / severe colitis (see comment)
- The colonic mucosa displays crypt architectural distortion and acute / mixed inflammatory infiltrate in the lamina propria, with / without cryptitis, with / without erosions / ulceration. Numerous apoptotic bodies are primarily located in the crypt bases and many mitotic figures are present. Viral inclusions are not present.
- Comment: The findings are consistent with drug / medication induced colitis, if corroborated by clinical history.
Differential diagnosis
- Infections:
- CMV, HSV or adenovirus:
- Viral inclusions on H&E or IHC
- Positive cultures or toxins in blood and stool
- CMV, HSV or adenovirus:
- Graft versus host disease:
- May show overlapping features; clinical correlation is essential
- Apoptosis without accompanying inflammation
- Apoptosis out of proportion to degree of inflammation
- Presence of eosinophils in the lamina propria favors drug induced mucosal injury
- Graft versus host disease shows fewer eosinophils and more endocrine cell aggregates in the lamina propria than mycophenolate mofetil induced colitis (Am J Surg Pathol 2013;37:1319)
- Chronic idiopathic inflammatory bowel disease (IBD):
- Features may overlap, correlation with clinical history is essential
- IBD shows typical features of chronicity (crypt distortion, basal lymphoplasmacytosis, left sided Paneth cell metaplasia)
- Apoptosis and atrophic crypts with attenuated epithelium are more typical of drug / chemotherapy related colitis
- Ischemic colitis:
- Features may overlap; correlation with clinical history is essential
- Atrophic surface epithelium and crypts lined by mucin depleted colonocytes (withered appearance)
- Paucity of inflammatory cells
- Eosinophilic appearance of lamina propria
Practice question #1
Histopathological changes in patients with chemotherapy induced colitis are nonspecific and challenging to diagnose without clinical correlation. Which characteristic could be attributed to chemotherapy induced colitis in an appropriate clinical context?
- Atrophic surface epithelium with loss of goblet cells, atrophic crypts with withered appearance, eosinophilic appearance of lamina propria
- Basal lymphoplasmacytosis, crypt architectural distortion, cryptitis and crypt microabscesses
- Crypt abscesses with exploding crypts (summit lesions) and pseudomembrane on the mucosal surface
- Crypt architectural distortion with apoptosis, loss of goblet cells, loss of crypts, mild inflammation in lamina propria including scattered neutrophils and eosinophils
Practice answer #1
D. Crypt architectural distortion with apoptosis, loss of goblet cells, loss of crypts, mild inflammation in lamina propria including scattered neutrophils and eosinophils. Chemotherapy associated colitis shows a number of histological features in variable combinations; prominent among these are the presence of apoptosis, crypt architectural distortion, loss of goblet cells and loss of crypts. The degree and composition of the inflammatory infiltrate is variable and usually mild.
Answer B is incorrect because basal lymphoplasmacytosis, in association with crypt architectural distortion, is typical of chronic idiopathic inflammatory bowel disease. Answer C is incorrect because cryptitis with summit lesions is characteristic of pseudomembranous colitis caused by Clostridioides difficile. Answer A is incorrect because atrophic appearance of the surface epithelium and crypts with loss of goblet cells are characteristic features of ischemic mucosal injury (ischemic colitis).
Comment Here
Reference: Chemotherapy induced colitis
Answer B is incorrect because basal lymphoplasmacytosis, in association with crypt architectural distortion, is typical of chronic idiopathic inflammatory bowel disease. Answer C is incorrect because cryptitis with summit lesions is characteristic of pseudomembranous colitis caused by Clostridioides difficile. Answer A is incorrect because atrophic appearance of the surface epithelium and crypts with loss of goblet cells are characteristic features of ischemic mucosal injury (ischemic colitis).
Comment Here
Reference: Chemotherapy induced colitis
Practice question #2
What is the etiology of diarrhea and abdominal pain in this patient?
- Patient developed diarrhea following a recent course of antibiotics
- Patient has a history of breast cancer
- Patient has a history of chronic idiopathic inflammatory bowel disease
- Patient returned from a cruise with severe abdominal cramps
Practice answer #2
B. Patient has a history of breast cancer. The biopsy shows numerous apoptotic bodies and mitotic figures, including ring mitoses. The latter represent metaphase mitosis and are characterized by condensed chromatin in a ring shape within the center of the cell. Ring mitoses are typical of drugs that interrupt the mitotic spindle, which is essential for chromosomal movement during cell division; taxanes and colchine are poster boys for drugs that interrupt the mitotic spindle and result in ring mitoses. Taxanes are widely used in chemotherapy, including for breast cancer.
Answer C is incorrect because ring mitoses are not a feature of chronic idiopathic inflammatory bowel disease. Answer D is incorrect because cruise ships provide conducive environments for infectious colitis; the chief culprit is norovirus. Norovirus is not associated with ring mitoses. Answer A is incorrect because diarrhea following a course of antibiotics is usually associated with pseudomembranous colitis due to Clostridioides difficile. Ring mitoses are not a feature of C. difficile pseudomembranous colitis.
Comment Here
Reference: Chemotherapy induced colitis
Answer C is incorrect because ring mitoses are not a feature of chronic idiopathic inflammatory bowel disease. Answer D is incorrect because cruise ships provide conducive environments for infectious colitis; the chief culprit is norovirus. Norovirus is not associated with ring mitoses. Answer A is incorrect because diarrhea following a course of antibiotics is usually associated with pseudomembranous colitis due to Clostridioides difficile. Ring mitoses are not a feature of C. difficile pseudomembranous colitis.
Comment Here
Reference: Chemotherapy induced colitis
