Necrotizing lymphadenitis (NEL) has been reported to be a reactive process described under differing terminology by Fujimoto et al. (1972), Kikuchi (1972), Wakasa et al. (1973) and other Japanese pathologists. Recently, this type of lymphadenitis has also been reported in America and Europe. In Japan, NEL is observed more frequently in the northern area, however, no characteristic seasonal occurrence has been noted. The disease affects young females more than males, particularly from the third and fourth decades onwards. Common cold-like symptoms, lymphadenopathy of the cervical region and leukopenia are characteristic clinical findings in the early stages. Morphological features of the involved lymph nodes include the presence of numerous immunoblasts, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Tubular inclusions are observed ultrastructurally. Immunohistochemical studies of peripheral blood using monoclonal antibodies have revealed that the helper/suppressor (Leu 3a/2a) ratio increases gradually with the clinical course because of a decrease in Leu 2a + cells. The pathogenesis of NEL is uncertain, but it has been speculated that there is cytolytic infection of lymphocytes by a virus or other organism, accompanied by secondary blastic transformation of suppressor T-lymphocytes.

We report the clinicopathological and immunohistological findings of nine cases of necrotizing lymphadenitis, consisting of four cases of familial infection and five cases of recurrence. Fever, cervical lymphadenopathy, leucopenia and swelling of the tonsils are characteristic clinical findings. Morphological features of the lymph nodes include the presence of immunoblasts, plasmacytoid T cells, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Ultrastructurally, tubuloreticular structures are observed not only in lymphoid cells, but in vascular endothelial cells. Immunological studies of peripheral blood using monoclonal antibodies disclose that CD 8+ (Leu 2a+; suppressor/cytotoxic) cells predominate at the onset, but they gradually decrease with the clinical course and the ratio of CD 4+: CD 8+ (helper:suppressor) increases as the disease progresses. However, in the affected lymph nodes, CD4+ (Leu 2a+: helper/inducer) cells often increase with the clinical progression, but the ratio of CD 4+:CD 8+ in the lymph nodes does not correlate with clinical progression. In addition, Ki-67+CD 8+ cells are more often seen than Ki-67+CD 4+ cells. It is suggested that necrotizing lymphadenitis is an infectious disease in which CD 4+ cells are disrupted and CD 8+ cells undergo transformation to blastoid cells. This results in a change in the ratio of T subsets.

This clinicopathological, immunohistochemical, electron microscopic, and serological study of 382 cases (148 male, 234 female) of necrotizing lymphadenitis (NEL) in Japan confirms NEL as a self-limited disease with characteristic clinical features: high fever (38-40 °C), painful cervical lymphadenopathy (88.3 %), and leukopenia (under 4,000/mm(3)) without seasonal occurrence. Patient age varied from 5 to 80 years, but 62.8 % was younger than 30 years. There were five recurrent cases and four familial cases. In several cases, elevated serum aminotransaminase and antinuclear antibodies were found. Early in the disease, peripheral blood CD8+ cells were more abundant than CD4+ cells, but CD8+ cells decreased gradually with clinical progression, leading to an increasing ratio of CD4+/CD8+ cells during clinical course. Morphological features of involved lymph nodes are numerous CD8+ large immunoblasts, smaller CD4+ lymphocytes, plasmacytoid dendritic cells, histiocytes, and macrophages, the latter with phagocytized CD4+ apoptotic lymphocytes. Granulocytes are generally absent. These characteristics suggest that NEL is a reactive disease characterized by diploid disrupted CD4+ cells and CD8+ cells transforming to blastic cells. The etiology of the disease remains unknown, although viral infection is suggested, and its pathogenesis might include autoimmunity. Clinical characteristics and cytological and histological findings on lymph node biopsies can improve NEL diagnosis.

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