Kaposi Sarcoma - Human Herpesvirus 8

Human herpesvirus 8 (HHV8) is associated with Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and primary effusion lymphoma (PEL) which occur almost exclusively in immunocompromised patients.

Diagnosis

Indications for Testing

  • Patient presenting with tumors suggestive of human herpesvirus 8 (HHV8) infection
  • Pretransplantation surgery – assess risk of Kaposi sarcoma (KS) after transplant (polymerase chain reaction [PCR] only)

Laboratory Testing

  • HHV8 PCR testing
    • Positive result confirms viral infection
    • Does not confirm HHV8 disease

Histology

  • Biopsy required to confirm diagnosis
  • Classic pathology on biopsy
  • Immunohistochemistry
    • HHV8 immunostaining – usually positive
    • CD30 (Ki-1) – positive in primary effusion lymphoma (PEL), negative in multicentric Castleman disease (MCD)
    • CD138 (Syndecan-1) – negative in MCD, positive in PEL
    • MUM1/IRF4 – positive in MCD and PEL

Differential Diagnosis

Background

Epidemiology

  • Incidence
    • KS incidence varies by world region and type
      • 1/100,000 in U.S.
      • 1/20 HIV-infected individuals
  • Age
    • Primary infection may be acquired from early childhood through adulthood
    • Age at presentation depends on form of disease (see Clinical Presentation)
  • Transmission
    • Predominantly via saliva
    • Also via blood, sexual contact, and transplants

Organism

  • Herpesvirus – double-stranded DNA
  • Also called Kaposi sarcoma-associated herpesvirus
  • ​Etiologic agent of three tumors
    • KS
    • MCD – plasmablastic form
    • PEL

Risk Factors

  • Immune deficiency or suppression
    • HIV
    • Drugs (eg, cyclosporine)
    • Inherited deficiencies (rare cause)
      • OXO4O deficiency
      • STIM1 deficiency
      • Wiskott-Aldridge syndrome
      • Interferon-gammaR1 deficiency

Clinical Presentation

  • KS
    • Classic form
      • U.S. – usually in males >60 years of Jewish or Mediterranean descent
      • Predominant purple lesions on lower extremities
    • Endemic forms
      • Adult – 30-50 years, resident of sub-Saharan Africa
        • Locally aggressive skin lesions, massive lower extremity edema
      • Childhood – <10 years, Bantu ethnicity
        • Generalized lymphadenopathy – particularly cervical region
        • Highly aggressive – death within 2 years
    • Epidemic form
      • Males >30 years with HIV
      • More common in men having sex with men
      • Aggressive tumor with systemic involvement
    • Transplant form
      • Tends to develop within months after transplant
      • Cutaneous involvement usually presents first
      • Course is similar to HIV-KS
  • MCD
    • Also called angiofollicular lymph node hyperplasia
      • Plasmablastic form
    • Sex – M:F, equal
    • Usually presents during 30s-40s
      • Most common in HIV-positive patients
      • Other at risk groups include transplant patients
    • Localized mediastinal masses or lymphadenopathy
    • Generalized malaise, night sweats, fever, anorexia, weight loss
    • May have clonal gammopathy or immune dysfunction
    • Some progress to PEL or B-cell lymphoma
  • PEL
    • Almost exclusively in immunocompromised patients
      • Typically males with HIV age 30-60 years
    • Rarely obvious solid tissue tumors – extracavitary form has been identified
    • Effusions present in pleural, pericardial, and/or abdominal cavities
    • May be associated with KS or MCD

ARUP Lab Tests

Detect and quantify herpesvirus 8 (HHV8)

Negative result (<3.8 log copies/mL or <6,670 copies/mL) does not rule out the presence of PCR inhibitors in the patient specimen or HHV8 DNA concentrations below the level of detection of the test

Inhibition may also lead to underestimation of viral quantitation

Aid in histologic diagnosis of HHV8

Stained and returned to client pathologist; consultation available if needed

Medical Experts

Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®