Colon (tumor & nontumor)
Noninfectious colitis
Lymphocytic colitis

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Martha M. Yearsley, M.D.

Topic Completed: 28 July 2020

Minor changes: 28 July 2020

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PubMed Search: lymphocytic colitis [title] colon

Martha M. Yearsley, M.D.
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Cite this page: Yearsley MM. Lymphocytic colitis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colonlymphocytic.html. Accessed August 10th, 2020.
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
Sites
Pathophysiology
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
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
Case reports
Treatment
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

Intact crypt architecture

Lamina propria expansion

Lamina propria expansion

Mixed lamina propria inflammatory infiltrate

Mixed lamina propria inflammatory infiltrate

Increased surface intraepithelial lymphocytes

Increased surface intraepithelial lymphocytes


Crypt intraepithelial lymphocytes

Crypt intraepithelial lymphocytes

Surface epithelial damage

Surface epithelial damage

Lymphocytic colitis and celiac disease

Lymphocytic colitis and celiac disease

Positive stains
Negative stains
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
Board review style question #1

Which of the following histologic findings best describes colonic mucosa in lymphocytic colitis?

  1. Crypt architectural distortion, basal lymphoplasmacytosis and crypt abscesses
  2. Depleted lamina propria, increased crypt apoptosis and crypt distortion
  3. Intraepithelial lymphocytes, surface epithelial damage, intact crypt architecture and lamina propria expansion
  4. Intraepithelial lymphocytes, thick subepithelial collagen band with entrapped inflammatory cells
  5. Lamina propria hyalinization, hemorrhage and withering crypts
Board review 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.

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?

  1. Idiopathic inflammatory bowel disease
  2. Infectious colitis
  3. Ischemic colitis
  4. Lymphocytic colitis
  5. Normal histology
Board review 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.

Reference: Lymphocytic colitis

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