Pathology Outlines

Colon (tumor & nontumor)

Infectious colitis

CMV

Author: Nalini Bansal, M.D.

Editorial Board Member: Raul S. Gonzalez, M.D.

Topic Completed: 1 November 2017

Minor changes: 27 July 2020

Revised: 9 January 2019, last major update November 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: CMV colitis[TI] OR cytomegalovirus colitis[TI] colon

Page views in 2019: 10,307

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Table of Contents

Cite this page: Bansal N. CMV. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonCMV.html. Accessed August 6th, 2020.

Definition / general

Cytomegalovirus (CMV) is a double stranded DNA virus belonging to the herpesvirus group (World J Gastroenterol 2009;15:4327)
Infection is usually seen in immunocompromised and debilitated patients, usually due to reactivation of latent infection
In immunocompetent patients, disease is related to primary infection
- Infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosis syndrome
Tissue invasive CMV results from the hematogenous spread of CMV
- Gastrointestinal (GI) CMV disease is the most common manifestation of tissue invasive CMV (Am J Transplant 2013;13:93)

Essential features

Cytomegalovirus (CMV) is a double stranded DNA virus belonging to the herpesvirus group
Infection is usually seen in immunocompromised and debilitated patients in setting of transplant, use of immunosuppressive drugs, AIDS
Infection mainly occurs due to reactivation of latent infection
Most common sites of involvement are esophagus and colon
Gastrointestinal bleeding is most common clinical presentation
Gold standard for diagnosis is histological diagnosis with immunohistochemistry (IHC)
Computed tomography scan and barium enema are considered the best imaging modalities for diagnosing CMV colitis
Microscopy shows cytomegalic cells with basophilic intranuclear inclusions, usually of endothelial / mesenchymal cells
Treatment consists of induction and maintenance therapy with antiviral drugs, such as ganciclovir or valganciclovir

Terminology

CMV infection: refers to presence of detectable CMV levels in the human body
CMV disease: CMV disease relates to symptoms due to CMV

ICD coding

B25.8: other cytomegaloviral diseases

Epidemiology

Virus is prevalent in adults, with 50 - 80% of the general population possessing an antibody to CMV by age 35 (Dis Colon Rectum 2004;47:722)
Seroprevalence is highest in developing countries throughout Africa and Asia (Rev Infect Dis 1990;12:S701)
Seroprevelance also varies by race and ethnicity; infection seen at early age among non-Hispanic blacks (16.3 years) and Mexican Americans (17.5 years) compared with non-Hispanic whites (29.3 years) (BMC Infect Dis 2007;7:71)
Infection can be acquired during birth, breast feeding, close contact, sexual contact, transfusion or with organ transplant (Scand J Gastroenterol 2010;45:1295)

Sites

Most common sites of CMV related gastrointestinal involvement are the esophagus and colon

Pathophysiology

Infection is usually seen in immunocompromised and debilitated patients, usually due to reactivation of latent infection; hematogenous spread of virus favors tissue invasive CMV infection
CD4+ and CD8+ T cells play an important role in controlling viral replication
CD4 cell counts of < 50 cells/µL in AIDS patients predispose to tissue invasive CMV disease (Arch Intern Med 1998;158:957)

Etiology

CMV virus

Clinical features

Gastrointestinal bleeding is the most common initial presentation of CMV colitis (Hepatogastroenterology 2012;59:2137)
Other features, including diarrhea, fever and abdominal pain, are common presenting symptoms (Scand J Infect Dis 1998;30:559)
Can mimic common colitides (Arch Pathol Lab Med 2016;140:854)
Patients with extraocular CMV disease often have concurrent CMV retinitis; thus, any patient diagnosed with CMV gastrointestinal disease should have a formal ophthalmologic examination
Classic mononucleosis can occur due to CMV in immunocompetent patients, and presents as protracted fevers and lassitude in the setting of absolute lymphocytosis and atypical lymphocytes (Am J Med Sci 1978;276:325)

Diagnosis

Gold standard for CMV colitis is histological diagnosis
Diagnosis based upon the following triad: clinical symptoms of gastrointestinal disease, visualization of characteristic lesions on endoscopy and intranuclear or cytoplasmic inclusions on pathology (AIDSinfo: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV Infected Adults and Adolescents [Accessed 6 November 2017])

Laboratory

Histology:
- Gold standard test
- Inclusions on histology with positive immunohistochemistry for CMV
Serology:
- Detection of CMV IgM antibodies: indicates acute infection
- Fourfold increase in titer of CMV IgG specific antibodies 2 - 4 weeks apart indicates acute infection
CMV DNA test: polymerase chain reaction (PCR) or hybrid capture is used to detect viral DNA in blood, plasma, leucocytes, tissue or stool
- Kandiel et al. propose that a CMV DNA cutoff level of 25,000 copies/mL in whole blood is a reasonable level for initiating antiviral treatment, with quantification by real time PCR (Am J Gastroenterol 2006;101:2857)
CMV culture: time consuming (1 - 3 weeks) and has lower sensitivity than newer techniques (antigen testing, PCR)

Radiology description

Computed tomography (CT) scan and barium enema are considered the best imaging modalities for diagnosing CMV colitis
CT scan may reveal colonic wall thickening
- "Accordion sign" may be seen, defined as alternating edematous haustral folds separated by transverse mucosal ridges filled with oral contrast material
- "Target" and "double / fat halo" signs can also be seen
- Both these signs signify edema with surrounding hyperemia
Barium enema may reveal stricture, mucosal irregularity and ulceration or thumbprinting (Arch Pathol Lab Med 2016;140:854)

Prognostic factors

Despite aggressive clinical manifestations, the prognosis of CMV colitis is good if diagnosed and treated early

Case reports

65 year old immunocompetent man with acute colonic obstruction secondary to CMV induced colonic stricture (BMJ Case Rep 2013 Sep 10;2013)

Treatment

Antiviral drugs: given as induction and maintenance therapy
Induction therapy: ganciclovir or valganciclovir
- Intravenous ganciclovir is dosed as 5 mg/kg/dose every 12 hours or oral valganciclovir (900 mg twice daily) for 3 - 6 weeks
Maintenance therapy: is required if there is concurrent retinitis or recurrent gastrointestinal disease after induction therapy has been discontinued
- Consists of valganciclovir, 900 mg given once daily (AIDSinfo: Guidelines for Prevention and Treatment of Opportunistic Infections in HIV Infected Adults and Adolescents [Accessed 6 November 2017])

Clinical images

Images hosted on other servers:

Diffuse inflammation

Ulcerating mass

Gross description

Well demarcated ulcerations, ulceroinfiltrative changes and pseudomembrane formation  (Hepatogastroenterology 2012;59:2137)

Gross images

Images hosted on other servers:

Ulceration and erythema

Ulceration secondary to CMV colitis

Terminal ileum

Caecum

Multiple, small punctate ulcers in the mucosa

Microscopic (histologic) description

CMV infected cells are cytomegalic cells, typically two to fourfold larger than normal, containing basophilic intranuclear inclusion bodies (Cowdry bodies) surrounded by a clear halo, giving the appearance of an owl's eye
Cells show a thickened nuclear membrane and smaller granular intracytoplasmic inclusions
Many of these infected cells can be seen surrounding blood vessels, as the most commonly infected cells are endothelial cells and mesenchymal cells (World J Gastroenterol 2009;15:4327)
Other features include architectural distortion with shortening of the crypts and glandular branching, cryptitis, crypt abscesses, basal lymphoplasmacytic cellular infiltrates and focal mucin depletion with reactive epithelial atypia, which can simulate inflammatory bowel disease (IBD) (Am Surg 2007;73:58)
Submucosal vasculitis, thrombus of microvessels and necrosis may also be seen

Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Dr. Nalini Bansal:

Cytomegalovirus inclusions in endothelial cells

Cytomegalovirus immunohistochemistry positive

Images hosted on other servers:

Cytomegalovirus inclusions

CMV inclusions - immunocompetent patient

Superficial ulceration

Enlarged nuclei containing basophilic inclusions

Figures A, B

Giant cell with inclusion body

Crypt with multiple apoptotic cells

Mass-like lesion

Epithelial cytomegalic cells

CMV+ cells

Positive cells in ascending and sigmoid colon

Positive stains

Immunohistochemistry for CMV

Negative stains

Other viral marker immunohistochemistry, such as adenovirus

Molecular / cytogenetics description

Polymerase chain reaction (PCR) DNA amplification
- Note: PCR DNA levels in the colon are not related to viremia levels measured in the blood
Detection of viral mRNAs coding for the pp67 protein has been proposed for quantifying CMV viremia (Hum Pathol 2014;45:48)

Differential diagnosis

Graft versus host disease: no viral inclusions
Inflammatory bowel disease: no viral inclusions
Ischemic colitis: no viral inclusions

Board review style question #1

CMV is a:

dsDNA virus
dsRNA virus
ssDNA virus
ssRNA virus

Board review answer #1

A. dsDNA virus

Board review style question #2

Most common site for CMV induced GI infection is:

Colon
Duodenum
Ileum
Stomach

Board review answer #2

A. Colon

Board review style question #3

Tissue invasive CMV disease usually occurs when:

CD4 count is < 50 cells/µL
CD4 count is > 50 cells/µL
Patients are immunocompetent
None of the above

Board review answer #3

A. < 50 cells/µL

Board review style question #4

The most common clinical presentation of CMV GI disease is:

Abdominal pain
Diarrhea
Fever
GI bleeding

Board review answer #4

D. GI bleeding