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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.

Histiocytic necrotizing lymphadenitis: A clinico-pathologic study of 45 cases with in situ hybridization for Epstein-Barr virus and hepatitis B virus