Background

This virus is a member of the Herpes family. It is commonly abbreviated CMV. It has gained noteriety as an important pathogen in immunocompromised patients, particulary AIDS patients. Subclinical infections are common amongst the general population. It is only when a patient's immune system is damaged and diminished that clinical infections may occur.

CMV may attack any organ in the body. AIDS patients are particularly prone to CMV retinitis which can lead to blindness. Other common manifestations of the disease include a colitis, esophagitis, myelitis, encephalopathy, and pneumonitis.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	CMV

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
BRAIN TUMORS
Lack of association of cytomegalovirus with human brain tumors. Lau SK, Chen YY, Chen WG, Diamond DJ, Mamelak AN, Zaia JA, Weiss LM. 1Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.	Mod Pathol. 2005 Jun;18(6):838-43. Abstract quote   Cytomegalovirus (CMV) is thought to possess oncogenic properties and has been linked with a number of human malignancies. CMV infection was recently described in association with malignant gliomas. The intent of the present study was to further investigate the reported association between CMV and malignant gliomas. Tissue from 22 brain tumors of various histologic types and grades, four normal brains, six breast carcinomas, six colon carcinomas, six lung carcinomas, and six sarcomas were evaluated for the presence of CMV by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemical methods. None of the brain tumors or normal brain tissue tested demonstrated evidence of CMV pp65 or early nuclear proteins by immunohistochemistry. In addition, no CMV RNA or DNA was detected in these cases by in situ hybridization and PCR. None of the carcinomas or sarcomas evaluated were positive for CMV by immunohistochemistry, in situ hybridization, or PCR. The findings of the present study suggest that CMV is not significantly associated with brain tumors in humans.
POSTSPLENECTOMY
Postsplenectomy Cytomegaloviral Mononucleosis Marked Lymphocytosis, TCRg Gene Rearrangements, and Impaired IgM Response Xiang Y. Han, MD, PhD, etal.	Am J Clin Pathol 2005;123:612-617 Abstract quote People who have undergone splenectomy mount a poor IgM response to bacterial polysaccharide vaccines. Whether this defect is true during natural bacterial and viral infections is unknown. We present 2 cases of postsplenectomy cytomegalovirus (CMV)-induced mononucleosis with impaired IgM but normal to augmented IgG response. The cases presented initial diagnostic challenges owing to a prolonged course of infection, marked lymphocytosis (peak lymphocyte count, 27,900/µL [27.9 × 109/L]), clonal T-cell proliferation with T-cell receptor g gene rearrangements, and remote history of splenectomy. However, the acute nature of the infections, serial determinations of the anti-CMV IgM and IgG, exclusion of other causes, and detection of CMV in the blood established the diagnosis and revealed the deranged antibody response. The infections resolved without specific treatment. These cases suggest that the spleen might be a primary site for specific anti-CMV IgM response.

 

CLINICAL VARIANTS	CHARACTERIZATION
PERINEAL ULCERS
Cytomegalovirus neuritis in perineal ulcers. Ramdial PK, Dlova NC, Sydney C. Department of Anatomical Pathology, Nelson R Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa Department of Dermatology, Nelson R Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa.	J Cutan Pathol 2002 Aug;29(7):439-44 Abstract quote BACKGROUND: Although a range of cytomegalovirus (CMV)-induced cutaneous manifestations is described in AIDS patients, skin involvement in immunocompromised patients is rare, and intraneural CMV inclusions or CMV neuritis has not been documented in skin biopsies. METHODS AND RESULTS: Cutaneous biopsies of CMV lesions were collected prospectively for 12 months. The morphology, sites and symptomatology of the individual lesions, associated systemic illnesses, treatment schedules and disease outcome were recorded. A total of nine biopsies were obtained from three females who presented with extensive painful perineal ulceration and disseminated cutaneous ulcers, nodules and plaques. Clinically, herpes simplex virus (HSV) ulceration was diagnosed and treatment with acyclovir was initiated after biopsies from the natal cleft, perineum and neck were obtained. All were superficial and demonstrated HSV infection. Only the natal cleft biopsy demonstrated coexistent CMV inclusions. Suboptimal healing necessitated two further biopsies from each patient, none of which demonstrated HSV inclusions. Three of four deep perineal biopsies demonstrated CMV inclusions within nerves attended by a lymphocytic infiltrate and architectural disturbances. Two deep cutaneous biopsies of the trunk and abdominal wall confirmed CMV in extraneural locations only. One superficial perineal biopsy did not demonstrate any viral inclusion. CONCLUSIONS: In documenting CMV neuritis in painful perineal ulcers, the histopathological spectrum of perineal CMV ulcers is expanded, a cutaneous neurotropic characteristic of CMV is presented and a direct role for CMV in the pathogenesis of pain is suggested. CMV latency within perineal nerves is also revisited as another potential site of CMV reactivation in immunocompromised patients, and another potential site for possible venereal transmission of CMV infection. The exclusive presence of HSV in initial superficial biopsies highlights the need for optimally biopsied tissue to confirm the coexistence of CMV infection.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Large intranuclear eosinophilic to amphophilic body surrounded by a clear space One or more small rounded basophilic granular masses in cytoplasmic perinuclear region
VARIANTS
GASTROINTESTINAL TRACT
Human cytomegalovirus infection of the gastrointestinal tract in apparently immunocompetent patients. Maiorana A, Baccarini P, Foroni M, Bellini N, Giusti F. Department of Morphological and Forensic Sciences, Pathological Anatomy Section, University of Modena, Italy.	Hum Pathol. 2003 Dec;34(12):1331-6. Abstract quote   Human cytomegalovirus (HCMV) infection is usually reported in immunocompromised patients. This study reports 11 cases of HCMV infection of the gastrointestinal (GI) tract diagnosed in apparently immunocompetent hosts. The median age of the patients studied was 76 years, and the major presenting symptoms were diarrhea, epigastric pain, and abdominal discomfort. The large intestine was involved in 6 cases, the stomach in 4 cases, and the lower esophagus in 1 case. Endoscopy revealed ulcers or hypertrophic folds in the GI tract and single ulcers or erosions in the colon and rectum. Light microscopy showed chronic inflammatory infiltrate in the lamina propria in all cases. The diagnosis of HCMV infection was based on the histological and immunohistochemical identification of HCMV inclusion bodies in different cell types, including epithelial, endothelial, stromal, and smooth muscle cells. Both "classical" inclusions, characterized by an "owl's eye" appearance, and atypical inclusions were found. For all patients, no apparent causes of immunodeficiency were detected at the time of diagnosis of HCMV infection. At follow-up, however, 4 patients were found to harbor a malignant tumor (ie, pancreas, lung, Vater's papilla, and extrahepatic bile duct) at an interval of 2 to 5 months after the diagnosis of HCMV infection. Especially in elderly patients, HCMV infection of the GI tract might be an early clue to the presence of immunologic defects induced by an underlying neoplasia.
SKIN	Am J Dermatopathol 2000;22:397-407 Cutaneous infection is rare but may manifest as viral inclusions within the endothelial cells, fibrocytes, and inflammatory cells Other sites include the eccrine ductal epithelium
	Am J Dermatopathol 1999;21:487-490 CMV induced syringosquamous metaplasia
Mucocutaneous Presence of Cytomegalovirus Associated With Human Immunodeficiency Virus Infection Discussion Regarding Its Pathogenetic Role Esteban Daudén, etal.	Arch Dermatol. 2001;137:443-448 Abstract quote Objectives To investigate the significance of cytomegalovirus (CMV) in mucocutaneous lesions in patients with human immunodeficiency virus (HIV), and to elucidate its pathogenetic role in lesions genesis. Design Retrospective (study 1) and prospective (studies 2 and 3) surveys. Setting Departments of Dermatology, Pathology, and Microbiology at a university hospital in Madrid, Spain. Patients Seventeen HIV-infected patients with CMV presenting any type of mucocutaneous lesions (study 1); 27 HIV-positive patients with mucocutaneous vesicles and/or ulcers of any type and location (study 2); and 12 severely immunosuppressed HIV-positive volunteers (study 3). Interventions Mucocutaneous biopsy specimens from the lesions (studies 1 and 2) and from nonlesional skin (study 3) were analyzed by light microscopy, immunohistochemical analysis, and microbiological analysis (standard viral culture and shell-vial technique). Main Outcome Measures Clinical data; histologic, immunohistochemical, and microbiological findings. Results (1) Studies 1 and 2: Most of the lesions where CMV was found were ulcers localized mainly on perianal, genital, and perigenital areas, usually as part of polymicrobial infections, particularly herpes simplex and varicella-zoster virus infections. The finding of CMV was confirmed in all cases by light microscopy; microbiological analysis was rarely useful. The finding of mucocutaneous CMV inclusions allowed their early detection in extracutaneous locations. (2) Study 3: Cytomegalovirus was present on healthy skin of the perianal area in 3 patients, and on the forearm in 1 patient. Conclusion Cytomegalovirus does not play any significant pathogenetic role at least in most of the cutaneous lesions where it is found.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
Immunoperoxidase	Monoclonal antibodies now available
DIFFERENTIAL DIAGNOSIS	CHARACTERIZATION
PERIKARYA OF GASTROINTESTINAL GANGLION CELLS
Colorectal intramucosal perikarya of ganglion cells. Tunru-Dinh V, Li-Cheng Wu M. Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine.	Am J Clin Pathol. 2005 Aug;124(2):269-72. Abstract quote   It generally is believed that perikarya of ganglion cells in the human colorectum are confined to plexuses that lie deep to the mucosa, and that intramucosal perikarya are rare. We retrospectively reviewed 100 specimens from biopsies of normal and abnormal mucosa to further characterize intramucosal perikarya. The presence of intramucosal perikarya, their number, location, and grouping were recorded. Twenty-one specimens (21.0%) contained intramucosal perikarya. Intramucosal perikarya occurred throughout the colorectum in the muscularis mucosae or lamina propria and in normal mucosa, acute self-limited colitis, inflammatory bowel disease, cytomegalovirus-associated colitis, hyperplastic polyps, tubular adenomas, and high-grade intraepithelial neoplasia. In some specimens, intramucosal perikarya morphologically resembled microgranulomas or cytomegalovirus-infected cells. We demonstrated that intramucosal perikarya of ganglion cells are surprisingly common in normal and abnormal mucosa. Awareness of intramucosal perikarya is necessary to avoid confusion with microgranulomas or cytomegalovirus-infected cells.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Treatment	Ganciclovir, Foscarnet and Cidofovir have been shown to slow down the progression of CMV, although they cannot cure the illness Ganciclovir in the pill form can sometimes be used after receiving two weeks of IV
CMV retinitis	Ganciclovir, Foscarnet and Cidofovir A Vitrasert can continually release Ganciclovir into the eye

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Microscopic Photo of CMV in the Lung
Microscopic Photo of CMV in the Adrenal Gland
Microscopic Photo of CMV in the Renal Tubules

Last Updated August 5, 2005

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