Detection of human herpesvirus DNA in Kikuchi-Fujimoto disease and reactive lymphoid hyperplasia

Abstract

Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a subacute inflammatory disorder most often seen in young women with clinicopathologic features suggestive of an infectious etiology. The most commonly suspected infectious agents in KFD are the human herpesviruses EBV, HHV6, HHV7 and HHV8. In order to identify herpesviruses in KFD, we have compared the frequency of detection of herpesvirus DNA with a recently developed real time PCR method, EBER in situ hybridization, and EBV latent membrane protein (LMP) immunostaining in 30 cases of KFD and 12 cases of reactive lymphoid hyperplasia (RLH). EBV DNA was commonly detected, while HSV2, CMV, HHV6, and HHV7 DNA were seldomly detected, and HSV1, VZV, and HHV8 DNA were not detected in KFD. EBV was also commonly detected in RLH. EBER-positive cells with apoptotic features were identified in necrotizing regions of many KFD cases, and LMP-positive cell debris was detected in one case. Viable EBER-positive cells were identified in four of twelve RLH cases, and rare LMP positivity detected in three cases. These data lend support to the notion that the necrotizing lesions in KFD may in some cases be due to a vigorous immune response to EBV-infected lymphoid cells.

Keywords: Epstein-Barr virus; Herpesvirus; Kikuchi-Fujimoto disease; histiocytic necrotizing lymphadenitis; reactive lymphoid hyperplasia; real time PCR.

Figure 1

Necrotic zone in KFD with plasmacytoid dendritic cells, macrophages, immunoblasts, and small apoptotic bodies (H&E, 400×).

Figure 2

A. Necrotic zone with numerous CD68 positive plasmacytoid dendritic cells and macrophages (CD68 immunoperoxidase, 600×). B. Necrotic zone with numerous CD3 positive T cells (CD3 immunoperoxidase, 600×). C. Necrotic zone with few CD20 positive B cells (CD20 immunoperoxidase, 600×). D. Necrotic zone with viable EBER positive cells (EBER in-situ hybridization, 600×). E. Necrotic zone with apoptotic EBER positive cells (EBER in-situ hybridization, 1000×). F. EBV LMP1 positivity of phagocytic debris within viable histiocytes in KFD (LMP1 immunoperoxidase, 600×). G. Viable EBER positive cells in reactive lymphoid hyperplasia (EBER in-situ hybridization, 600×). H. A rare viable LMP1 positive lymphoid cell in reactive lymphoid hyperplasia (LMP1 immunoperoxidase, 1000×)