[Genotypic analysis of lethal midline granuloma].

So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported genotypic and immunopathological features in 3 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis/midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4 (Case 1), CD4 (Case 2), and CD2, CD3 (Case 3). Those cells were also found to be positive for HLA-DR, which indicated that they were activated T-cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cell neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 3 cases showed rearrangement of TCR gene, TCR beta and TCR gamma chain (Cases 1 and 2) and TCR beta and TCR delta chain (Case 3), whereas none of them showed rearrangement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within lethal midline granuloma. On the ground of immunohistological and genotypic studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a T-cell lymphoproliferative disorder.