Lymphocytic Colitis

Definition

• Colorectal disease characterized by an intramucosal chronic inflammatory infiltrate in the absence of crypt distortion

Alternate/Historical Names

• Microscopic colitis
  • Used by some to refer to both lymphocytic and collagenous colitis, while to others it refers to only lymphocytic colitis

Diagnostic Criteria

• Increased lymphocytes and plasma cells in lamina propria of colon
  • Increased eosinophils and mast cells may also be seen in lamina propria
• Increased intraepithelial lymphocytes in surface epithelium between crypts
  • >20 / 100 epithelial cells
    • Normal is 5 / 100
    • Mucosa overlying lymphoid nodules must be excluded from evaluation
    • T cell phenotype
  • May also involve crypts
  • A rare cryptal variant has been described
    • Increased intraepithelial lymphocytes only in crypts, not the surface epithelium
      • Same behavior as usual lymphocytic colitis
  • Paucicellular lymphocytic colitis has been proposed (Goldstein 2004)
    • 11 intraepithelial lymphocytes / 100 epithelial cells
    • Same behavior as usual lymphocytic colitis
    • It has been proposed that this is a different entity (Fernandez-Banares 2009)
    • We prefer to diagnose this as “colonic intraepithelial lymphocytosis” with a comment
• Surface mucosa typically flattened, mucin depleted
  • Focal detachment may be seen
  • No overt ulceration
• Occasional neutrophils up to cryptitis may be seen in up to 38% of cases
  • Infrequently focally prominent with crypt abscesses
    • If present, infection and inflammatory bowel disease must be ruled out
• Multinucleated giant cells may be seen in rare cases
  • Located immediately below the surface epithelial layer
• No significant crypt distortion
  • Mild crypt irregularity has been described in 4% of cases
• May be variably distributed in colon
  • A single normal biopsy does not rule out the disease
• No thickened subepithelial collagen layer
• Terminal ileum may be involved by intramucosal lymphocytosis
  • Normal levels reported from 2-8 T cells / 100 enterocytes
• Several other GI diseases must be ruled out (see Differential Diagnosis)
• Lymphocytic colitis and collagenous colitis have been proposed to be related
  • They share an identical chronic inflammatory pattern and are distinguished only by the presence of a thickened collagen layer only in the latter
  • Cases are reported showing change from one to the other on sequential biopsies
  • Collagen deposition in collagenous colitis may be patchy, making interpretation of such observations difficult
  • Female:Male ratios originally reported as different
    • More recent studies find similar ratios of approximately 1-5:1 F:M (Kao 2009)

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates : 11/11/09, 12/3/09, 11/11/11, 1/28/12

Differential Diagnosis

• Similar findings may be seen in biopsies taken from a variety of processes:
• Diverticulosis
• Crohn disease
• Infectious colitis
• Autoimmune enteropathy
  • Usually pediatric
  • Usually more severe deep inflammation and crypt damage
• Celiac sprue
  • Up to 30% of celiac disease patients may have lymphocytic colitis-like findings
• If such diseases have not been ruled out clinically, the findings are best diagnosed as “Colonic Intraepithelial Lymphocytosis” with a comment describing the differential diagnosis
• Chronic colitis is a term best not used as a pathologic diagnosis
• Moderate numbers of lymphocytes and plasma cells are normal in the lamina propria of the large intestine
• The chronic changes associated with inflammatory bowel disease are better diagnosed as “crypt distortion” with a comment that they are consistent with chronic inflammatory bowel disease
• Lymphocytic colitis and collagenous colitis are distinguished by the presence of a thickened collagen layer only in the latter
• They both exhibit a prominent intramucosal lymphocytic infiltrate
• The thickened collagen layer may be variably distributed
  • Multiple biopsies may need to be examined

Clinical

• Intractable watery diarrhea
• No bleeding
• May be acute, chronic or intermittent
• Endoscopic appearance usually normal
• Occasionally shows edema or hyperemia
• No evidence of malabsorption
• Variable course
• May spontaneously resolve
• May be associated with autoimmune disease
• Arthritis
• Fibromyalgia
• Thyroiditis
• Sjogren syndrome
• Giant cell arteritis
• CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia)
• A wide variety of drugs have been implicated as causes, including NSADs (reviewed in Mahajan 2012)
• Up to 15% of cases are found to be associated with (or a manifestation of ) celiac disease
  • Lymphocytic colitis may be the initial presentation
• Age range 2-98 years
• Mean age 50’s
• Uncommon in children
• Treatment may include drugs ranging from loperamide to budesonide or other steroids, depending upon the severity of disease (reviewed in Yen 2011, Mahajan 2012)
  • Relapses are frequent

Bibliography

• Noffsinger A, Fenoglio-Preiser CM, Maru D, Gilinisky N.  Gastrointestinal Diseases, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 5, 2007.
• Lazenby AJ. Collagenous and lymphocytic colitis. Semin Diagn Pathol. 2005 Nov;22(4):295-300.
• Chang F, Deere H, Vu C. Atypical forms of microscopic colitis: morphological features and review of the literature. Adv Anat Pathol. 2005 Jul; 12(4):203-11.
• Rubio CA, Lindholm J. Cryptal lymphocytic coloproctitis: a new phenotype of lymphocytic colitis? J Clin Pathol. 2002 Feb;55(2):138-40.
• Goldstein NS, Bhanot P. Paucicellular and asymptomatic lymphocytic colitis: expanding the clinicopathologic spectrum of lymphocytic colitis. Am J Clin Pathol. 2004 Sep;122(3):405-11.
• Ayata G, Ithamukkala S, Sapp H, Shaz BH, Brien TP, Wang HH, Antonioli DA, Farraye FA, Odze RD. Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis. Am J Surg Pathol. 2002 Nov;26(11):1414-23.
• Fernández-Bañares F, Casalots J, Salas A, Esteve M, Rosinach M, Forné M, Loras C, Santaolalla R, Espinós J, Viver JM. Paucicellular lymphocytic colitis: is it a minor form of lymphocytic colitis? A clinical pathological and immunological study. Am J Gastroenterol. 2009 May;104(5):1189-98.
• Padmanabhan V, Callas PW, Li SC, Trainer TD. Histopathological features of the
  ileum in lymphocytic and collagenous colitis: a study of 32 cases and review of literature. Mod Pathol. 2003 Feb;16(2):115-9.
• Sapp H, Ithamukkala S, Brien TP, Ayata G, Shaz B, Dorfman DM, Wang HH, Antonioli DA, Farraye FA, Odze RD. The terminal ileum is affected in patients with lymphocytic or collagenous colitis. Am J Surg Pathol. 2002 Nov;26(11):1484-92.
• Yen EF, Pardi DS. Review of the microscopic colitides. Curr Gastroenterol Rep. 2011 Oct;13(5):458-64.
• Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH, Kanter MH, Wirio S, Conteas CN. Microscopic colitis: a large retrospective analysis from a health maintenance organization experience. World J Gastroenterol. 2009 Jul 7;15(25):3122-7.
  
• Mahajan D, Goldblum JR, Xiao SY, Shen B, Liu X. Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities. Adv Anat Pathol. 2012 Jan;19(1):28-38.