KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Report of two cases with anaplastic large cell morphology and plasmablastic immunophenotype

Abstract

Background: Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) associated lymphomas, which often develop in human immunodeficiency virus (HIV) infected patients with advanced AIDS, present predominantly as primary effusion lymphoma (PEL) or, less frequently, as "solid" extracavitary based lymphomas, associated with serous effusions. These last lymphomas, also called "solid PEL", have been reported before the development of an effusion lymphoma and after resolution of PEL. Interestingly, KSHV/HHV-8 associated lymphomas that present as solid or extracavitary based lesions in HIV seropositive patients without serous effusions have been reported recently.

Methods/results: This paper provides evidence for the existence of a previously undescribed KSHV/HHV-8 associated lymphoma in HIV seronegative patients without serous effusions. These lymphomas exhibit a predilection for the lymph nodes and display anaplastic large cell morphology. These tumours were completely devoid of common cell type specific antigens, including epithelial and melanocytic cell markers. B and T cell associated antigens and other commonly used lymphoid markers were absent or weakly demonstrable in a fraction of the tumour cells. Conversely, immunohistochemical studies showed strong immunostaining with plasma cell reactive antibodies.

Conclusions: Analysis of viral infection and immunohistological studies are of primary importance to define this lymph node based KSHV/HHV-8 associated lymphoma with anaplastic large cell morphology and plasmablastic immunophenotype occurring in HIV seronegative patients without serous effusions.

Figure 1

Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) associated “solid” lymphoma; case 1. (A) Immunohistochemistry for KSHV/HHV-8 open reading fragment 73 (ORF73) protein. The ORF73 protein is detected in the nucleus of almost all of the tumour cells (original magnification, ×40). (B) Polymerase chain reaction for KSHV/HHV-8 ORF72. A band compatible with the genomic sequence is detectable. Lane 1, DNA extracted from case 1; lane 2, DNA extracted from a positive control (CRO-AP/6 primary effusion lymphoma cell line); M, DNA molecular weight marker. (C) A lymph node infiltrated by large anaplastic cells exhibiting a sinusoid pattern of growth. Haematoxylin and eosin staining; original magnification, ×40. (D) Immunohistochemistry for cytoplasmic IgG showing that the tumour cells are positive for this antigen (original magnification, ×40). (E) Immunohistochemistry for MUM1/IRF4. All tumour cells show intense nuclear staining for MUM1/IRF4 (original magnification, ×40).

Figure 2

Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) associated “solid” lymphoma; case 2. (A) Immunohistochemistry for KSHV/HHV-8 open reading fragment 73 (ORF73) protein. The ORF73 protein is detected in the nucleus of almost all of the tumour cells (original magnification, ×40). (B) Polymerase chain reaction for KSHV/HHV-8 ORF72. A band compatible with the genomic sequence is detectable. Lane 1, DNA extracted from case 1; lane 2, DNA extracted from a positive control (CRO-AP/6 primary effusion lymphoma cell line); M, DNA molecular weight marker. (C) Immunohistochemistry for KSHV/HHV-8 viral interleukin 6 protein, with most tumour cells showing cytoplasmic staining for this antigen (original magnification, ×40). (D) Demonstration of Epstein-Barr virus (EBV) by EBV encoded small non-coding RNA in situ hybridisation (original magnification, ×40). (E) A lymph node infiltrated by large anaplastic cells. Several giant cells display multilobated nuclei. Haematoxylin and eosin staining; original magnification, ×40. (F) Immunohistochemistry for cytoplasmic IgG, with several tumour cells positive for this antigen (original magnification, ×40). (G) Immunohistochemistry for MUM1/IRF4. All tumour cells display intense nuclear staining for MUM1/IRF4 (original magnification, ×40).