Kaposi Sarcoma - Human Herpesvirus 8

Diagnosis

Indications for Testing

  • Patient presenting with rare tumor related to human herpesvirus 8 (HHV8)
  • Pretransplantation surgery – assess risk of Kaposi sarcoma after transplant (PCR only)

Laboratory Testing

  • HHV8 PCR testing – positive result confirms viral infection

Histology

  • 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

Clinical Background

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

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 from blood, sexual contact, transplants

Organism

  • Herpesvirus – double-stranded DNA
  • Also called Kaposi sarcoma-associated herpesvirus

Risk Factors

  • Immune deficiency

Clinical Presentation

  • Kaposi sarcoma
    • Classic form
      • In 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
    • Transplant form
      • Tends to develop within months after transplant
      • Cutaneous involvement usually presents first
    • Epidemic form
      • Males >30 years with HIV
      • More common in men having sex with men
      • Aggressive tumor with systemic involvement
  • Multicentric Castleman disease
    • Also called angiofollicular lymph node hyperplasia
    • Sex – M:F, equal
    • Usually presents during 30s-40s   
    • Localized mediastinal masses or lymphadenopathy
    • Generalized malaise, night sweats, fever, anorexia, weight loss
    • May have clonal gammopathy or immune dysfunction
  • Primary effusion lymphoma
    • Almost exclusively in immunocompromised patients
      • Typically males with HIV age 30-60 years
    • No obvious solid tissue tumors
    • Effusions present in pleural, pericardial, and/or abdominal cavities

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Kaposi Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 0055629
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Preferred test for diagnosing HHV8-related disease

Requires tissue sample 

   
Herpesvirus 8 DNA, Qualitative Real-Time PCR 2002996
Method: Qualitative Real-Time Polymerase Chain Reaction

Not the preferred test to confirm presence of HHV8 DNA; tissue is preferred specimen for diagnosing HHV8-related disease

   
Herpesvirus 8 (HHV-8) DNA, Quantitative Real-Time PCR 2008440
Method: Quantitative Real-Time Polymerase Chain Reaction

Not the preferred test to confirm presence of HHV8 DNA; tissue is preferred specimen for diagnosing HHV8-related disease

Detects viral loads <1,000 copies/mL

   
Herpes Virus 8 by Immunohistochemistry 2003932
Method: Immunohistochemistry

Aid in histologic diagnosis of HHV8

Stained and returned to client pathologist; consultation available if needed

   
CD30 (Ki-1) by Immunohistochemistry 2003547
Method: Immunohistochemistry

Aid in differential diagnosis of PEL and MCD

Stained and returned to client pathologist; consultation available if needed

   
CD138 (Syndecan-1) by Immunohistochemistry 2003812
Method: Immunohistochemistry

Aid in differential diagnosis of PEL and MCD

Stained and returned to client pathologist; consultation available if needed

   
MUM1/IRF4 by Immunohistochemistry 2003975
Method: Immunohistochemistry

Aid in differential diagnosis of MCD and PEL

Stained and returned to client pathologist; consultation available if needed