Colon

Infectious colitis

Cytomegalovirus (CMV)


Editorial Board Member: Aaron R. Huber, D.O.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Bindu Challa, M.D.
Martha M. Yearsley, M.D.

Topic Completed: 7 December 2021

Minor changes: 7 December 2021

Copyright: 2002-2022, PathologyOutlines.com, Inc.

PubMed Search: CMV OR cytomegalovirus colitis[title] colon pathology "last 5 years"[DP]

Bindu Challa, M.D.
Martha M. Yearsley, M.D.
Page views in 2021: 18,513
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Cite this page: Challa B, Yearsley MM. Cytomegalovirus (CMV). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonCMV.html. Accessed January 19th, 2022.
Definition / general
  • Cytomegalovirus (CMV) is a double stranded DNA virus and a member of human herpes virus family
  • Also known as herpes virus type 5
  • 3 patterns of CMV infection:
    • Latent infection
      • Most common, immunocompetent patients
    • Mononucleosis-like syndrome
      • Immunocompetent patients
    • Tissue invasive disease
      • Immunocompromised patients
  • Tissue invasive disease
    • Gastrointestinal tract is most commonly involved (30% of tissue invasive cases) (Virol J 2008;5:47)
Essential features
  • Double stranded DNA virus and a member of human herpes virus family
  • Tissue invasive disease, usually seen in immunocompromised patients
  • Most common sites of infection in gastrointestinal tract:
    • Colon
    • Esophagus
  • Symptoms:
    • Rectal bleeding (most common)
    • Diarrhea
    • Abdominal pain
    • Fever
    • Weight loss
  • Microscopy:
    • Cytomegalic cells with owl's eye intranuclear viral inclusions
    • CMV immunohistochemistry is the gold standard for diagnosis
Terminology
  • CMV infection
    • CMV antigens or antibodies in blood
  • CMV disease
    • Clinical symptoms and end organ damage
  • CMV colitis
    • Identification of characteristic intranuclear / intracytoplasmic inclusions on H&E sections
    • Identification of CMV specific antigens by immunohistochemistry (IHC) and clinical symptoms
ICD coding
  • ICD-10: B25.8 - other cytomegaloviral diseases
Epidemiology
Sites
  • Can involve any part of the gastrointestinal tract
  • Most common sites:
    • Colon
    • Esophagus
Pathophysiology
  • Spread by saliva, urine, respiratory droplets, sexual contact, breast milk and blood transfusions (Clin Microbiol Rev 1989;2:204, Nihon Rinsho 1998;56:179)
  • After initial infection, CMV resides latently in monocytes, fibroblasts, myeloid cells and endothelial cells
  • Tissue invasive disease in colon can lead to ulcerative changes, erosion into blood vessels (causing bloody diarrhea), inflammatory polyps, severe inflammation and vasculitis leading to ischemia and transmural necrosis
Etiology
  • Cytomegalovirus (CMV)
  • Most commonly in immunocompromised patients
    • History of AIDS, organ transplantation, hematologic malignancy, cancer therapy and corticosteroid therapy
  • Risk factors in immunocompetent patients:
    • Renal disease
    • Hemodialysis
    • Neurological disease
    • Rheumatic disease
    • Exposure to antibiotics
    • Antacids
    • Corticosteroid
  • Red blood cell transfusion within 1 month of diagnosis of colitis (Clin Infect Dis 2015;60:e20)
  • Severe ulcerative colitis (patients treated with high dose corticosteroids)
Clinical features
Diagnosis
  • Surgical resection specimen or biopsy: histopathologic diagnosis
  • Clinical symptoms, endoscopic findings, serologic testing, polymerase chain reaction (PCR) and culture
Laboratory
  • Histology:
    • Gold standard test
      • Immunohistochemistry (IHC) for CMV
        • Greater sensitivity than hematoxylin & eosin (H&E)
      • H&E can detect CMV infected cells
        • Cells larger than normal, containing intranuclear or intracytoplasmic inclusions
      • CMV infected cells can be confirmed by IHC staining
  • Serology:
    • Acute infection
      • CMV IgM antibodies
      • 4 times increase in titer of CMV IgG specific antibodies 2 - 4 weeks apart
    • CMV antigenemia
      • Predictor of clinical outcomes
      • Less sensitive for diagnosis of CMV colitis
    • Real time polymerase chain reaction (PCR) / CMV DNA quantification
      • Positive in only 50% of patients with biopsy proven CMV colitis / enteritis
    • CMV culture
      • High sensitivity and specificity for diagnosis of CMV colitis
      • Takes longer to obtain results (1 - 3 weeks)
      • May delay diagnosis and timely treatment (J Clin Microbiol 1993;31:2851)
Radiology description
  • Computed tomography:
    • Nonspecific findings
    • Bowel wall thickening
    • Mural edema
    • Pericolonic fat stranding
    • Free fluid, free air
    • Lymphadenopathy (Radiology 1985;155:585)
  • Endoscopic findings:
    • Easy bleeding, loss of vascular pattern, mucosal edema, erythema, mucinous exudate and wide mucosal defect
    • Mucosal defects, punched out ulcers (most common), longitudinal ulcers, irregular ulceration or cobblestone appearance (Emerg Radiol 2020;27:277)
Radiology images

Images hosted on other servers:

CT findings in a patient with CMV colitis

Prognostic factors
  • Excellent overall prognosis
  • Factors associated with poor prognosis and higher mortality (immunocompetent patients)
    • M > F
    • Age > 55 years
    • Patients requiring surgery
    • CMV colitis reactivation with ulcerative colitis, tends to have poorer prognosis
  • Timely diagnosis and treatment greatly improves clinical outcomes (StatPearls: Cytomegalovirus Colitis [Accessed 12 November 2021])
Case reports
Treatment
  • Intravenous (IV) ganciclovir (5 mg/kg twice daily)
  • After 3 - 5 days of IV ganciclovir, oral valganciclovir (900 mg, twice daily) (Clin Gastroenterol Hepatol 2015;13:949)
  • Foscarnet in ganciclovir resistant or tolerant cases
Clinical images

Contributed by Martha M. Yearsley, M.D.

Diffuse erythema

Pseudomembrane
formation

Irregular ulceration, loss of vascular pattern



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Diffuse inflammation

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Ulcerating mass

Gross description
  • Nonspecific findings
  • Inflamed mucosa, hyperemia, mucosal sloughing
  • Punched out ulcers, aphthous ulcers, exudate
  • Pseudomembrane formation (Arch Pathol Lab Med 2016;140:854)
Gross images

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Ulceration and erythema

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Ulceration secondary to CMV colitis


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Terminal ileum

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Cecum

Multiple, small punctate ulcers in the mucosa

Microscopic (histologic) description
  • Most commonly affected cells:
    • Endothelial cells
    • Mesenchymal cells
    • Macrophages
  • Larger (cytomegalic) cells:
    • Usually 25 - 35 micrometers
    • Typically 2 - 4 times larger than normal
  • Owl’s eye:
  • Thickened nuclear membrane
  • Coarse red intracytoplasmic granules (Int Med Case Rep J 2011;4:55)
  • Increased apoptotic bodies
  • Expansion of lamina propria by mixed inflammatory plasma cell rich infiltrate
  • Neutrophilic inflammation
  • Deep fissuring ulcers, cryptitis, crypt abscess, architectural distortion and pseudopolyp formation
  • Submucosal vasculitis and thrombosis of microvessels
Microscopic (histologic) images

Contributed by Martha M. Yearsley, M.D.

Enlarged cells in colonic lamina propria

Cytomegalic endothelial cells

Owl's eye and coarse red granules

Infected endothelial cells


Cytomegalic endothelial cells partially occluding vessel

Immunoreactivity with CMV immunostain

Scattered CMV positive cells

CMV positive endothelial cells

Positive stains
  • Immunohistochemistry for CMV
Negative stains
Molecular / cytogenetics description
  • Real time DNA PCR amplification method:
    • Rapid results, high negative predictive value
    • Contradictory reports regarding sensitivity
  • CMV DNA load > 250 copies/mg tissue may predict resistance to steroid treatment in ulcerative colitis (Am J Gastroenterol 2011;106:2001)
Videos

CMV colitis in ulcerative colitis and immunocompromised states

Sample pathology report
  • Colon, random, biopsy:
    • CMV colitis
    • Immunohistochemical stain for CMV is positive

  • Colon, colectomy:
    • CMV colitis in the background of severely active ulcerative pancolitis
    • Immunohistochemical stain for CMV is positive
    • Negative for dysplasia
Differential diagnosis
Board review style question #1


A 71 year old man presents with abdominal pain and diarrhea. Colonoscopy showed diffuse mucosal erythema and irregular ulcerations. The patient undergoes biopsy of the lesion. What is the infected cell and organism causing the histopathologic findings?

  1. Endothelial cell, adenovirus
  2. Endothelial cell, cytomegalovirus
  3. Epithelial cell, adenovirus
  4. Epithelial cell, cytomegalovirus
Board review style answer #1
B. Endothelial cell, cytomegalovirus. The images show cytomegalic endothelial cells with inclusions. Adenovirus typically affects epithelial cells and shows amphophilic nuclear inclusions.

Comment Here

Reference: Cytomegalovirus (CMV)
Board review style question #2
What is the gold standard method for diagnosing CMV colitis?

  1. CMV culture
  2. CMV DNA polymerase chain reaction (PCR) amplification method
  3. CMV serology
  4. Immunohistochemistry for CMV
Board review style answer #2
D. Immunohistochemistry for CMV

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Reference: Cytomegalovirus (CMV)
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