Colon
Noninfectious colitis
Lymphocytic colitis
Author: Martha M. Yearsley, M.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Last author update: 28 July 2020
Last staff update: 4 June 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: lymphocytic colitis [title] colon
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Yearsley MM. Lymphocytic colitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonlymphocytic.html. Accessed April 26th, 2024.
Definition / general
- Chronic nonulcerating colitis; subtype of microscopic colitis
- Common cause of chronic nonbloody diarrhea in older adults with normal or near normal colonoscopy and increased intraepithelial lymphocytes as the histologic hallmark
Essential features
- Cause of chronic watery diarrhea, often in older females
- Normal, edematous or mildly erythematous mucosa on endoscopy
- Colonic intraepithelial lymphocytosis (> 20 per 100 enterocytes) with diffuse increase in lamina propria inflammatory cells
ICD coding
- ICD-10: K52.832 - lymphocytic colitis
Epidemiology
- Overall incidence 4.85 per 100,000 person years (Am J Gastroenterol 2015;110:265)
- Older adults (50 - 70 years) but wide age range
- F > M
- F:M = 1.62 (Am J Gastroenterol 2015;110:265)
- No ethnic predilection
- 9 - 16% of patients undergoing colonoscopy for watery diarrhea (Eur J Gastroenterol Hepatol 2015;27:963)
Sites
- Worse in right than left colon (Neth J Med 2005;63:137)
- Rectal sparing in 8%
Pathophysiology
- Multifactorial (Inflamm Bowel Dis 2016;22:450)
- Impaired epithelial barrier
- Reaction to luminal antigens
- Genetic predisposition
- Smoking (Eur J Gastroenterol Hepatol 2017;29:587)
- Hormonal influence
- Abnormalities in fluid homeostasis
- Autoimmunity
- HLA-DQ2 and DQ1.3, HLD-DR3DQ2 haplotypes
- Bile acid malabsorption (Hepatogastroenterology 2002;49:432)
- Infection, viral or bacterial
- Medication induced (Am J Gastroenterol 2017;112:78)
- Acarbose, aspirin, beta blockers, carbamazepine, H2 receptor antagonists, NSAIDs, proton pump inhibitor, selective serotonin reuptake inhibitors (SSRI), statins, ticlopidine
Etiology
- Not clearly determined yet
Clinical features
- Classic symptom is chronic nonbloody watery diarrhea
- Other symptoms include urgency, fecal incontinence, abdominal pain, weight loss
- Some asymptomatic
- Associated autoimmune disorders (Gut 2004;53:536)
- Thyroiditis
- Celiac disease
- Diabetes mellitus
- Psoriasis
- Rheumatoid arthritis
Diagnosis
- Normal colonoscopy or mild nonspecific erythema or edema
- Biopsies from all segments of the colon, proximal to rectosigmoid
- Proximal to rectosigmoid
- Rectal biopsy alone cannot rule it out
- Proximal to rectosigmoid
Laboratory
- Mild anemia, elevated erythrocyte sedimentation
- Autoantibodies (ANA, ANCA, antithyroid peroxidase antibodies)
- Fecal leukocytes may be present
- Elevated fecal calprotectin
- Fecal eosinophil derived proteins
- Negative stool cultures, ova and parasites
- Negative lactose malabsorption test (Am J Gastroenterol 2017;112:78)
Radiology description
- Normal barium enema
Prognostic factors
- Benign clinical course, chronic intermittent or continuous (Clin Transl Gastroenterol 2019;10:e00071)
- Reduced risk of colorectal neoplasia including decreased prevalence of polyps (Dig Dis Sci 2012;57:161, Am J Gastroenterol 2015;110:1056)
Case reports
- 54 year old man with nasopharyngeal squamous cell carcinoma on pembrolizumab (Am J Gastroenterol 2018;113:629)
- 59 year old man with intractable diarrhea, weight loss and hypertension (Am J Case Rep 2019;20:111)
- 68 year old man with lymphocytic colitis diagnosis 40 years after ulcerative colitis (ACG Case Rep J 2018;5:e82)
Treatment
- Decrease risk factors:
- Smoking cessation
- Discontinuation of drugs
- Mild cases:
- Loperamide, cholestyramine, mesalazine, bismuth (Am J Gastroenterol 2017;112:78)
- Moderate to severe cases:
- Budesonide (Gastroenterology 2009;136:2092)
- Nonresponsive cases:
- Immunomodulators (azathioprine, 6-mercaptopurine), anti-TNF (J Crohns Colitis 2011;5:612)
- Surgical diversion (Dis Colon Rectum 2002;45:123)
Gross description
- Normal, edematous or mildly erythematous mucosa on endoscopy
Microscopic (histologic) description
- Increased intraepithelial lymphocytes (Hum Pathol 1989;20:18)
- > 20 IELs per 100 epithelial cells, away from lymphoid aggregates
- Increased lamina propria inflammatory cells
- Lymphocytes, plasma cells, eosinophils, occasional neutrophils
- Predominantly upper half of the mucosa
- Less prominent in left colon
- Preserved / intact crypt architecture (Hum Pathol 1989;20:18)
- Surface epithelial damage (Hum Pathol 1989;20:18)
- Flattening, mucin depletion, vacuolization, nuclear irregularities
- Unremarkable subepithelial collagen (< 10 μm)
- Rare acute cryptitis, crypt abscess (30 - 38% of cases) (Am J Surg Pathol 2002;26:1414)
- Focal and mild, not predominant
- Paneth cell metaplasia, rarely seen
- Less frequent findings:
- Subepithelial giant cells
- Ruptured crypt granulomas
Microscopic (histologic) images
Contributed by Martha M. Yearsley, M.D.
Intact crypt architecture
Lamina propria expansion
Mixed lamina propria inflammatory infiltrate
Increased surface intraepithelial lymphocytes
Crypt intraepithelial lymphocytes
Surface epithelial damage
Lymphocytic colitis and celiac disease
Positive stains
- CD3
- Not needed routinely
- May be helpful in borderline cases (Hum Pathol 2016;48:25)
Negative stains
- Negative for thickening of subepithelial collagen band by:
- Trichrome
- van Gieson
- Tenascin (Virchows Arch 2001;438:435)
Videos
Microscopic colitis
Sample pathology report
- Colon, random biopsies:
- Colonic mucosa with increased intraepithelial lymphocytes, consistent with lymphocytic colitis
Differential diagnosis
- Collagenous colitis:
- Thickening and qualitative abnormalities of subepithelial collagen band with mild increase in intraepithelial lymphocytes
- Inflammatory bowel disease (IBD):
- Architectural distortion
- Basal lymphoplasmacytosis
- Cryptitis, crypt abscesses
- Paneth cell metaplasia
- Acute infectious colitis:
- Edema
- Luminal, lamina propria, surface neutrophils and cryptitis
- No mononuclear inflammation or increased intraepithelial lymphocytes
- Checkpoint inhibitor induced colitis (Cancer 2019;125:1768):
- Scattered crypt apoptosis
- Basal lymphoplasmacytosis
- May otherwise mimic lymphocytic colitis; clinical history essential
- Autoimmune enteropathy:
- Loss of Paneth and goblet cells
- Basal crypt intraepithelial lymphocytes and apoptosis
- Crypt distortion and crypt abscesses
- No surface intraepithelial lymphocytosis
Additional references
Board review style question #1
Which of the following histologic findings best describes colonic mucosa in lymphocytic colitis?
- Crypt architectural distortion, basal lymphoplasmacytosis and crypt abscesses
- Depleted lamina propria, increased crypt apoptosis and crypt distortion
- Intraepithelial lymphocytes, surface epithelial damage, intact crypt architecture and lamina propria expansion
- Intraepithelial lymphocytes, thick subepithelial collagen band with entrapped inflammatory cells
- Lamina propria hyalinization, hemorrhage and withering crypts
Board review style answer #1
C. Intraepithelial lymphocytes, surface epithelial damage, intact crypt architecture and lamina propria expansion. Answer A best fits inflammatory bowel disease. Answer B is an apoptotic colopathy pattern of injury that can be seen in graft versus host disease and mycophenolate induced injury, for example. Answer D describes collagenous colitis and answer E corresponds to ischemic colitis.
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Reference: Lymphocytic colitis
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Board review style question #2
A 53 year old woman presents with a history of intermittent diarrhea of unexplained origin. The colonoscopy shows mild erythema throughout the colon. Based on representative images of random colon biopsies, what is the most likely diagnosis?
- Idiopathic inflammatory bowel disease
- Infectious colitis
- Ischemic colitis
- Lymphocytic colitis
- Normal histology
Board review style answer #2
E. Normal histology. The left image shows normal architecture. The intraepithelial lymphocytes on the right image are overlying a lymphoid aggregate. Intraepithelial lymphocytes should be evaluated away from the mucosal lymphoid aggregates.
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Reference: Lymphocytic colitis
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