Abstract and Introduction
Human herpesvirus 8 (HHV-8) is recognized as a major causal agent of Kaposi sarcoma (KS), and it has been detected in all epidemiologic variants of KS. Until now, detection of HHV-8 in paraffin-embedded sections was done mostly by using reverse transcriptase-polymerase chain reaction.
To assess the sensitivity and specificity of an anti-HHV-8 antibody and its potential usefulness for separating KS from its mimickers, we immunostained 72 KS samples and 108 samples of potential mimickers of KS with the monoclonal antibody latent nuclear antigen-1 (LNA-1; Advanced Biotechnologies, Columbia, MD). Cases of KS included all epidemiologic variants of the disease. Non-KS lesions included 34 angiosarcomas, 4 kaposiform hemangioendotheliomas, and 70 various benign vascular lesions. Immunostaining for CD31, CD34, and/or von Willebrand factor (factor VIII) also were performed in all cases.
All but 1 case of KS (sensitivity, 99%) and none of the non-KS lesions (specificity, 100%) stained with the LNA-1 anti-HHV-8 antibody.
The LNA-1 anti-HHV-8 antibody is a reliable marker of all variants of KS. Because KS mimickers are consistently negative for this marker, its use for diagnostic purposes is recommended.
Kaposi sarcoma (KS) is a vascular, often multicentric lesion characterized by 4 epidemiologic manifestations: classic, iatrogenic, endemic (ie, African), and associated with AIDS. The classic form of KS initially was described by Moriz Kaposi as a cutaneous sarcoma of elderly people (most patients are men and older than 50 years). Classic KS is observed chiefly in the Mediterranean region, Eastern Europe, and the Middle East. The iatrogenic variant is observed characteristically in a context of organ transplantation, long-term cytotoxic drug administration, and the use of corticoids or in autoimmune diseases. It generally occurs 24 months after the onset of therapy. In endemic (African) KS, male predominance is also a characteristic feature, but patients are usually younger (younger than 40 years). An often fatal, lymphadenopathic form occurring in children has been described in this KS form. Among the KS cases associated with acquired immunodeficiency states, AIDS-associated KS is the most frequent. Among HIV-infected patients, homosexuals and bisexuals are high-risk groups. KS is the main proliferating lesion in patients with AIDS, of whom 15% to 20% develop it. The clinical course and histopathologic manifestations of these 4 epidemiologic forms are roughly similar. Tumor sites include skin, mucosa (oropharynx and digestive tract), lymph nodes, and visceral organs.
In 1994, Chang et al identified 2 unique herpesvirus-like DNA sequences in AIDS-associated KS, sequences corresponding to human herpesvirus 8 (HHV-8), a virus of the γ subtype of the herpesvirus family. This virus is akin to herpesvirus saimiri, a virus that is responsible for lymphoproliferative lesions in new-world primates. HHV-8 DNA has been detected in virtually all epidemiologic forms of KS but not in the adjacent uninvolved skin of patients with KS or in unaffected subjects. Interestingly, whereas about 5% of the population worldwide probably is infected with HHV-8, the incidence of KS is less than 1/100,000. The presence of HHV-8 is now considered to be a major initiating event for the development of KS.[7,8] It is observed in the spindle cells of KS and in endothelial cells and also has been found in tumor leukocytes by some[3,9] but not all authors.
Until now, HHV-8 has been detected in KS by using polymerase chain reaction (PCR)[6,10,11] and only seldom by using immunochemical analysis applied to paraffin-embedded tumor tissue samples.[8,12,13]
By using PCR, HHV-8 has been detected in 95% to 100% of KS cases. This finding is important because it permits a firm diagnosis of KS in cases of exiguous or otherwise inadequate histologic material. Conflicting results have been reported in the literature about the presence of HHV-8 in angiosarcoma. By using PCR, some authors detected viral DNA in some angiosarcomas, whereas others did not.[11,12,15] In addition to KS, HHV-8 viral DNA also has been detected in a subset of myofibroblastic inflammatory tumors, in primary effusion lymphomas, and in multicentric Castleman disease.[16,17,18,19] The role of HHV-8 in the histogenesis of multiple myeloma is questionable.[20,21] Evidence of HHV-8 DNA also has been detected in a few non-Hodgkin lymphomas and in 1 Hodgkin lymphoma.
Am J Clin Pathol. 2004;121(3) © 2004 American Society for Clinical Pathology
Cite this: Human Herpesvirus 8 Immunostaining: A Sensitive and Specific Method for Diagnosing Kaposi Sarcoma in Paraffin-Embedded Sections - Medscape - Mar 01, 2004.