Forty-five cases of histiocytic necrotizing lymphadenitis (HNL) or Kikuchi-Fujimoto disease were reviewed clinico-pathologically and studied for Epstein-Barr virus (EBV) and hepatitis B virus (HBV) by in situ hybridization to assess their causative role. Histologically, the lymph nodes typically showed relatively well defined paracortical lesions composed of large atypical mononuclear cells, histiocytes, and karyorrhectic nuclear debris. Mild to moderate degree of coagulation type necrosis was present in 24 cases. Clinical features did not vary greatly from previously described female preponderance, young age onset, subacute cervical lymphadenopathy, and frequent leukopenia, except for a few cases with recurrent disease over 8-9 years. Serologic tests revealed EBV IgG antibody in one case, HBV surface antibody in 11 cases and HBV surface antigen in 2 cases. In situ hybridization was performed on 41 cases using internal repeat 1 fragment DNA and EBV-coded small RNA (EBER-1) for EBV, and pan-HBV DNA probe for HBV detection, and showed that all cases were negative for EBV or HBV genome. Our results suggest EBV or HBV may not have causative role in the pathogenesis of HNL.
Adolescent ; Adult ; Aged ; Child ; DNA, Viral/analysis ; Female ; Hepatitis B Virus/genetics/*isolation & purification ; Herpesvirus 4, Human/genetics/*isolation & purification ; Histiocytes/pathology/*virology ; Human ; In Situ Hybridization ; Lymphadenitis/pathology/*virology ; Male ; Middle Age

OBJECTIVETo study the clinical manifestation, pathologic features and immunophenotype of histiocytic necrotizing lymphadenitis (HNL).

METHODSThe clinicopathologic data of 84 patients with HNL from 2005 to 2014 were retrospectively studied. Immunohistochemical staining using EliVision method for CD20, PAX5, CD3, CD45RO, CD4, CD8, CD56, CD68, CD123, granzyme-B, TIA1 and MPO was carried out. In-situ hybridization for Epstein-Barr virus RNA was performed on archival lymph node biopsy tissue.

RESULTSImmunohistochemical study showed that the lesional cells were predominantly histiocytes (CD68+), plasmacytoid dendritic cells (CD123+) and T lymphocytes (CD3+ and CD45RO+). Clusters of CD68-positive cells with strong and diffuse MPO expression were identified. T lymphocytes with CD4 and CD8 positivity were noted. CD56+ natural killer cells and CD20+/PAX5 B cells were rare. Apoptosis-related markers, including TIA1 and granzyme B were expressed by T lymphocytes and histiocytes in lymph nodes of HNL. In-situ hybridization for Epstein-Barr virus RNA was positive in only 10.0% of the cases.

CONCLUSIONSHNL shows no specific clinical and laboratory findings. Recognition of the characteristic histopathologic changes in lymph node biopsy of HNL is the key to correct diagnosis. Immunohistochemical study using a panel of markers, including CD3, CD4, CD8, MPO, CD123, granzyme-B and TIA1, is helpful in the differential diagnosis of HNL.

Antigens, CD ; analysis ; Biomarkers ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Granzymes ; analysis ; Herpesvirus 4, Human ; genetics ; Histiocytes ; pathology ; Histiocytic Necrotizing Lymphadenitis ; complications ; immunology ; pathology ; virology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; methods ; Lymph Nodes ; RNA, Viral ; analysis ; Retrospective Studies ; T-Lymphocytes ; immunology ; pathology