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

• Kaposi sarcoma
  • Infectious
    • M. tuberculosis
    • Fungal disease – molds, yeasts
  • Foreign body granuloma
  • Amelanotic melanoma
• Castleman disease
  • Lymphoma
    • Hodgkin
    • B-cell
    • T/NK-cell
  • Plasmacytoma
  • Infectious
    • M. tuberculosis
    • Fungal disease – molds, yeasts
• PEL
  • Metastatic carcinoma
  • Lung carcinoma
  • Empyema 
  • Mesothelioma

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