In order to assess the clinical and pathologic significance of the immunologic characterization of human malignant lymphomas, biopsy tissues are obtained from patients referred to the Clinical Center for treatment and/or diagnosis. The neoplastic cells are characterized as to their origin from T cells, NK cells, B-cells, or histiocytes, and in addition can be identified as belonging to specific developmental and functional subpopulations. Immunophenotypic data are correlated with histologic and clinical findings, with the goal of defining distinctive clinicopathologic entities. The relevance of immunophenotype as correlated with response to therapy is explored. Immunophenotypic and morphologic data are correlated with molecular and cytogenetic findings, to define the pathogenesis of disease entities. This information is used to define new clinicopathologic entities, and to further refine the definition of currently recognized diseases. It is also used as a basis for immunotherapy, either alone or in concert with conventional chemotherapy and radiotherapy. The functional repertoire of neoplastic lymphoid cells is studied by evaluating the production of chemokines and cytokines using molecular and immunohistochemical methods. These data are correlated with histological and clinical parameters. In the past year we have characterized the occurrence of marginal zone lymphomas in the pediatric and young adult age group. Nodal marginal zone lymphomas are more common in males than females, and occur at a younger median age than extranodal marginal zone lymphomas, which are more common in females. We also have characterized blastic NK cell lymphomas, as a form of primitive hematopoietic malignancy frequently involving the skin with a high incidence of bone marrow involvement and poor clinical outcome. This tumor has a unique immunophenotype (CD4+, CD56+, CD3-, TDT+) and lacks rearrangement of the antigen receptor genes. Its lineage is uncertain, although an origin from NK cells has been speculated. We studied the cutaneous manifestations of lymphomatoid granulomatosis (LYG), previously characterized as an EBV-associated lymphoproliferative disorder. Vasculitis and panniculitis are frequent sequelae of LYG. EBV is infrequently localized to cutaneous lesions. These data provide evidence for a chemokine/cytokine-mediated pathogenesis for the cutaneous lesions. These and other data have been incorporated in the recently completed WHO Classification of Tumors of the Haematopoietic and Lymphoid Tissues,which is now accepted as the international standard.
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