Kaposi's sarcoma–associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8–related lymphomas?

Lazzi, Stefano; Bellan, Cristiana; Amato, Teresa; Palummo, Nazzareno; Cardone, Concetta; D'Amuri, Alessandro; De Luca, Fabio; Beyanga, Medard; Facchetti, Fabio; Tosi, Piero; Leoncini, Lorenzo

doi:10.1016/j.humpath.2005.08.020

« Previous Next »Human Pathology
Volume 37, Issue 1 , Pages 23-31, January 2006

Kaposi's sarcoma–associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8–related lymphomas?☆

Stefano Lazzi, MD, PhD
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Cristiana Bellan, MD, PhD
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Teresa Amato, BSc
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Nazzareno Palummo, MSc
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Concetta Cardone, MSc
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Alessandro D'Amuri, MD
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Fabio De Luca, MSc
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Medard Beyanga, MD
- Bugando Medical Center, Mwanza, Tanzania
Fabio Facchetti, MD
- Department of Pathology, University–Spedali Civili of Brescia, 25100 Brescia, Italy
Piero Tosi, MD
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Lorenzo Leoncini, MD
- Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
- Corresponding author. Dipartimento di Patologia Umana ed Oncologia, Sezione di Anatomia Patologica, Via delle Scotte, 653100 Siena, Italy.

Received 21 February 2005; accepted 25 August 2005.

Summary

We set out to analyze the presence of Kaposi's sarcoma–associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in different neoplasms occurring in East Africa, a region characterized by a high KSHV/HHV-8 seroprevalence rate and endemic Kaposi's sarcoma (KS). Our results suggest that, in endemic regions of Africa, KSHV/HHV-8 is predominantly associated with KS, independently of HIV status. During the course of this study, other important information came to light. We found the presence of KSHV/HHV-8 in 2 cases of lymph nodes partially involved by Burkitt's lymphoma and KS and in 1 case of multicentric Castleman disease. Our immunophenotypic and molecular data seem to suggest 2 different mechanisms of viral infection are at work in lymphoid cells. On one hand, when B cells show a latent phase infection with KSHV/HHV-8, after the germinal center reaction, naive B cells become resting memory B cells, similarly to Epstein-Barr virus–infected B cells. On the other hand, when lytic genes such as vIL6 are expressed in naive B cells, they may be driven to differentiate into plasmablasts without undergoing germinal center reaction. Interestingly, among KSHV/HHV-8–positive cases, in those in which there was also lymphoma, the neoplastic cells were negative for KSHV/HHV-8. This further confirms that KSHV/HHV-8 is involved in the neoplastic transformation of only certain types of lymphoma, probably in relation to their precursor infected cell. In conclusion, the maturation stage of KSHV/HHV-8–positive B cells as well as the type of viral infection may well determine the morphological, phenotypic, and clinical characteristics of KSHV/HHV-8–associated lymphomas.

Keywords: Kaposi's sarcoma–associated herpesvirus, Human herpesvirus 8, Lymphoma