Kaposi Sarcoma - Human Herpesvirus 8

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

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

Laboratory Testing

  • HHV8 PCR testing – positive result confirms viral infection
    • Does not confirm HHV8 disease – confirmation requires biopsy

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

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 – 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
  • ​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
      • 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
    • 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
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

Human Herpesvirus 8 (HHV-8) by Quantitative PCR 2013089
Method: Quantitative Polymerase Chain Reaction

Limitations 

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

Follow-up 

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

Ariza-Heredia EJ, Razonable RR. Human herpes virus 8 in solid organ transplantation Transplantation. 2011; 92(8): 837-44. PubMed

Bhutani M, Polizzotto MN, Uldrick TS, Yarchoan R. Kaposi sarcoma-associated herpesvirus-associated malignancies: epidemiology, pathogenesis, and advances in treatment Semin Oncol. 2015; 42(2): 223-46. PubMed

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

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

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

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

Morrison BJ, Labo N, Miley WJ, Whitby D. Serodiagnosis for tumor viruses Semin Oncol. 2015; 42(2): 191-206. PubMed

Pietrosi G, Vizzini G, Pipitone L, Di Martino G, Minervini MI, Iacono L, Conaldi PG, Grossi P, Lamonaca V, Galatioto L, Gruttadauria S, Gridelli B. Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study Am J Transplant. 2011; 11(12): 2715-23. PubMed

Razonable RR. Human herpesviruses 6, 7 and 8 in solid organ transplant recipients Am J Transplant. 2013; 13 Suppl 3: 67-77; quiz 77-8. PubMed

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

Zamora MR. 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 DA, Perkins SL, Tripp S, Coffin CM, Florell SR. 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: August 2016