Skip to main content
Download PDF

Volume 4 Supplement 2

Proceedings of the 11th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI): Basic, Epidemiologic, and Clinical Research

Pathology of rituximab-induced Kaposi sarcoma flare: role of B-cell depletion

Infectious Agents and Cancer volume 4, Article number: P33 (2009) Cite this article

Background

Kaposi sarcoma (KS) flare (exacerbation) may occur following therapy with corticosteroids, as part of the immune reconstitution inflammatory syndrome seen with highly active antiretroviral therapy (HAART), and after rituximab therapy. The exact mechanism responsible for iatrogenic KS flare is unclear. Therefore, the aim of this study was to investigate the pathologic features in cases of AIDS-associated KS flare.

Methods

Two cases of AIDS-associated cutaneous KS flare were identified following rituximab therapy. Tissue biopsies obtained from these KS flare lesions were compared to similar controls (AIDS-KS samples of similar stage from patients who had not received rituximab) by means of immunohistochemistry using vascular makers (CD34, CD31), monoclonal antibodies to human Herpesvirus-8 (HHV-8) gene products (LNA-1, K5), as well as B-lymphocyte (CD20) and T-lymphocyte (CD3, CD4, CD8) markers.

Results

One patient was a 36-year-old male, HIV-positive for 2 years (CD4 T-lymphocyte count 363 cells/mm3; HIV viral load >100,000 copies/ml), and the other a 44-year-old male, HIV-positive for 5 years (CD4 T-lymphocyte count 443 cells/mm3; HIV viral load <75 copies/ml), who had both received rituximab therapy for multicentric Castleman disease. The former manifested with cutaneous KS after 7 days, and the later patient with skin and lymphadenopathic KS flares within 3 months of receiving rituximab. In the control cases both CD3 and CD20 cells were present, with a preponderance of T-lymphocytes identified. In the KS flare specimens, there were only T-cells present with a notable absence of B-lymphocytes. In all control and flare KS cases T-cell subsets showed CD8 > CD4. CD20+ B-cell depletion in the KS flare case of the 36-year-old patient occurred concomitantly with activation of the HHV-8 immediate early gene protein K5. KS flares in both patients were successfully treated with liposomal doxorubicin and valganciclovir.

Conclusion

Rituximab-induced KS flare appears to be related to a modification in the host immune system, most notably with complete absence of B lymphocytes in the KS lesion. B-cell depletion with rituximab in patients at risk for KS development may activate HHV-8, resulting in unwanted KS flare. Effective management of iatrogenic KS flare therefore depends upon the control of HHV-8 viremia in conjunction with specific chemotherapy for KS.

Author information

Affiliations

  1. Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts, USA

    L Pantanowitz & S Marconi

  2. Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, USA

    K Früh

  3. Virginia Mason Medical Center, Seattle, Washington, USA

    D Aboulafia

  4. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    BJ Dezube

Authors
  1. L Pantanowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Früh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Aboulafia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Marconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. BJ Dezube
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Pantanowitz.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Pantanowitz, L., Früh, K., Aboulafia, D. et al. Pathology of rituximab-induced Kaposi sarcoma flare: role of B-cell depletion. Infect Agents Cancer 4, P33 (2009). https://doi.org/10.1186/1750-9378-4-S2-P33

Download citation

Keywords

  • Liposomal Doxorubicin
  • Immune Reconstitution Inflammatory Syndrome
  • Valganciclovir
  • Castleman Disease
  • Multicentric Castleman Disease

Infectious Agents and Cancer

ISSN: 1750-9378

Contact us