Human Herpesvirus 8 - Kaposi Sarcoma

Indications for Testing

Patient presenting with rare tumor related to HHV8
Pre-transplantation 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

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.

Epidemiology

Incidence – varies by world region and type
- 1/100,000 in U.S. for KS
- 1/20 HIV-infected persons for KS
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 and 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 and 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