Kaposi Sarcoma - Human Herpesvirus 8

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

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

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

Herpes Virus 8 by Immunohistochemistry 2003932
Method: Immunohistochemistry

Herpesvirus 8 DNA, Qualitative Real-Time PCR (INACTIVE as of 04/04/16: Refer to February 2016 Hot Line for Replacement Test: 2013089, ACTIVE 02/16/16) 2002996
Method: Qualitative Real-Time Polymerase Chain Reaction

Herpesvirus 8 (HHV-8) DNA, Quantitative Real-Time PCR (INACTIVE as of 04/04/16: Refer to February 2016 Hot Line for Replacement Test: 2013089, ACTIVE 02/16/16) 2008440
Method: Quantitative Real-Time Polymerase Chain Reaction

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

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

MUM1/IRF4 by Immunohistochemistry 2003975
Method: Immunohistochemistry

General References

Carbone A, Gloghini A. HHV-8-associated lymphoma: state-of-the-art review. Acta Haematol. 2007; 117(3): 129-31. PubMed

Cronin D, Warnke R. Castleman disease: an update on classification and the spectrum of associated lesions. Adv Anat Pathol. 2009; 16(4): 236-46. PubMed

Du M, Bacon C, Isaacson P. Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and lymphoproliferative disorders. J Clin Pathol. 2007; 60(12): 1350-7. PubMed

El-Osta H, Kurzrock R. Castleman's disease: from basic mechanisms to molecular therapeutics. Oncologist. 2011; 16(4): 497-511. PubMed

Wen K, Damania B. Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett. 2010; 289(2): 140-50. PubMed

Zamora M. DNA viruses (CMV, EBV, and the herpesviruses). Semin Respir Crit Care Med. 2011; 32(4): 454-70. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Wada D, Perkins S, Tripp S, Coffin C, Florell S. Human herpesvirus 8 and iron staining are useful in differentiating Kaposi sarcoma from interstitial granuloma annulare. Am J Clin Pathol. 2007; 127(2): 263-70. PubMed

Medical Reviewers

Last Update: December 2015