Cytomegalovirus Lymphadenitis

Cytomegalovirus Lymphadenitis

Sa A. Wang, MD

CMV lymphadenitis. This field shows that the sinus is expanded by monocytoid B cells between 2 large, reactive follicles (left and right).

The high-power view of CMV lymphadenitis shows a large cell infected by CMV, which has a prominent intranuclear inclusion surrounded by a halo and multiple, small cytoplasmic inclusions.



  • Cytomegalovirus (CMV)


  • Lymphadenitis caused by CMV infection



  • Member of β-herpes virus family

    • Double-stranded DNA virus with 162 hexagonal protein capsomeres surrounded by lipid membrane

  • Lytic virus that causes cytopathic effect in vitro and in vivo

  • Productive (lytic) infection leads to synthesis of immediate-early, early, and late viral proteins

  • Viral DNA has been detected in monocytes, dendritic cells, megakaryocytes, and myeloid progenitor cells in bone marrow

  • Virus infects T cells but not B cells

  • Monocytes and endothelial cells are also commonly infected by CMV

  • Can be transmitted by a number of means

    • Person-to person via saliva, respiratory secretions, or sexual fluids

    • Blood transfusions

    • Transplacental passage

  • Immunology

    • Body produces neutralizing antibodies upon primary infection

    • Cell-mediated immunity is most important factor in controlling CMV infection

CMV Infection in Immunocompetent Host

  • Mostly primary infection

CMV Infection in Immunocompromised Patients

  • Reactivation of CMV, either iatrogenic or secondary to underlying medical conditions

    • Solid organ or bone marrow transplantation

    • Acquired immunodeficiency syndrome (AIDS)

CMV Infection in Pregnancy

  • Maternal primary CMV infection

  • In utero transmission of CMV, either due to primary CMV infection or reactivation

    • Can be lethal with damage to central nervous system (CNS)



  • Incidence

    • Infection with CMV is common as determined by presence of serum antibodies

      • In developed countries, 60-80% of population is infected by adulthood

      • In developing countries, most children are infected by 3 years of age

      • > 90% of homosexual men are infected by CMV

    • Age, geography, cultural and socioeconomic status, and child rearing practices affect prevalence

  • Age

    • Congenital

      • 1% of newborns are infected by CMV

    • Perinatal infection due to

      • Maternal cervicovaginal secretions during delivery

      • Breast feeding

    • Daycare toddlers

      • Horizontal transmission of virus to both children and adult daycare center workers

    • Adolescence

      • Sexual transmission

    • Immunocompromised patients, all ages

    • Blood or tissue exposure, all ages

  • Gender

    • No sex preference

  • Ethnicity

    • No preferences


  • Immunocompetent patients

    • Asymptomatic or flu-like syndrome

    • Symptoms similar to infectious mononucleosis-type syndrome, but milder

      • Fever of unknown origin

      • Lymphadenopathy, often cervical

      • Pharyngitis

      • Hepatosplenomegaly

      • Blood: Lymphocytosis with atypical lymphocytes

    • CMV reactivation is common in critically ill immunocompetent patients

      • Can be associated with prolonged hospitalization

  • Immunocompromised patients

    • Organ transplant recipients and patients with immunodeficiency syndromes

    • Interstitial pneumonitis

      • Respiratory symptoms, fever, and dyspnea

      • Can be life-threatening

    • Gastrointestinal infection

      • Esophagus: Dysphagia

      • Upper gastrointestinal tract: Ulcer

      • Colon: Bloody diarrhea, fever, and abdominal pain

    • CMV retinitis

      • Frequent in HIV patients with a CD4 count < 50 cells/µL

      • Decreased/impaired visual acuity, floaters, and loss of visual fields on 1 side

      • Can progress to bilateral involvement if untreated

    • Neurologic manifestations

      • CMV encephalitis

      • Guillain-Barré syndrome

      • Other peripheral neuropathies

    • CMV hepatitis

      • Often subclinical

      • Unexplained fever

      • Abnormal liver function tests

      • Portal vein thrombosis (rare)

    • Pericarditis and myocarditis

    • Myeloradiculopathy

    • Disseminated CMV infection is criterion for AIDS

  • Congenital infection

    • At birth

      • Small size for gestational age

      • Hepatosplenomegaly

      • Petechiae and purpura of the skin, jaundice

      • Neurologic involvement: Microcephaly, seizures, and feeding difficulties

    • Sequelae in children

      • Sensorineural hearing loss

      • Chorioretinitis

      • Microcephaly, seizures, or paresis/paralysis

      • Mental retardation

Laboratory Tests

  • Serology

    • Recent and acute CMV infection

      • Detection of CMV-specific IgM antibodies

      • At least 4x increase in CMV-specific IgG titers in specimens obtained at least 2-4 weeks apart

    • To determine past exposure to CMV infection

      • If positive for past infection, monitor those at risk for CMV reactivation syndromes

      • If negative for past infection, monitor for new infection if transplanted with CMV seropositive organ

  • Early antigen detection (shell vial cultures)

    • Methods

      • Centrifugation of clinical samples (e.g., urine, blood) to increase absorption of virus

      • Infected cell monolayers incubated with monoclonal antibodies specific for CMV

    • Results typically available within 2-3 days

      • Accelerates time to diagnosis

  • CMV antigenemia assays

    • Methods

      • Using monoclonal antibodies specific to pp65 lower matrix protein of CMV to detect CMVinfected leukocytes in peripheral blood

      • Results are reported as number of cells with staining per total number of cells counted

    • Advantage

      • Results generally available within 24 hours

      • Antigenemia appears to correlate with viremia

  • Molecular methods for detecting CMV

    • Hybrid Capture System CMV DNA test

      • Signal amplification method using RNA probe that targets CMV

    • COBAS Amplicor test

      • PCR assay that amplifies 365 base pair region of CMV polymerase gene

    • Nucleic acid sequence-based amplification (NASBA)

      • Detects both immediate-early gene UL123 (IE1) and late gene expression (pp67)

    • Utility

      • Sensitive and specific for organ transplant patients

      • Not sensitive in detecting acute CMV infection

  • Other laboratory findings

    • Heterophile antibody is negative

    • Hematologic findings: Absolute lymphocytosis and atypical lymphocytes

      • CD4:CD8 ratio reversed

      • Increased large granular lymphocytes, NK cells

  • Viral cultures

    • CMV grows slowly in cell culture

      • Not a rapid confirmatory test

    • Positive result does not confirm active CMV disease

    • Limited sensitivity


Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cytomegalovirus Lymphadenitis
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