Leukemias and lymphomas of thymic differentiation

Neoplasms of thymic T-cell derivation include two closely related malignancies: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma. The recognition of these tumors as distinct biologic entities dates back to the early 1970s, when patients with these diseases were found to have tumor cells that formed spontaneous rosettes with sheep erythrocytes. In the last decade, however, the growth of new technologies and availability of new reagents has enabled us to characterize this group of disease with more precision. When studied with a panel of monoclonal antibodies, there is tremendous phenotypic diversity in the types of T-cell leukemias that are encountered. In spite of this diversity, a few general facts have become apparent. To a first approximation, thymic T-cell malignancies can be related to stages of normal T-cell development. Surprisingly, in spite of the overall similarity between T-ALL and T-lymphoblastic lymphoma, the antigenic phenotypes encountered suggest a biologic difference between these two diseases. Although there is not currently any single reagent that permits recognition of T-ALL or lymphoblastic lymphoma in all cases, a combination of technologic approaches using conventional morphology and histochemistry, immunologic studies, and, in some cases, newer genetic studies should permit great precision in the definition of this disease. The clinical picture of T-cell ALL of lymphoblastic lymphoma has traditionally been one of a poor prognosis disease with high WBC count, bulky adenopathy, and mediastinal mass. Although encountering this clinical presentation should suggest the T-cell phenotype, not all patients with T-cell leukemia will fit this stereotype. Clinical studies have also served to provide support for the expanding biologic definition of T-cell neoplasia, particularly insofar as it has been demonstrated that patients with T antigen-positive but E rosette-negative ALL behave like other patients with T-cell disease. In short, patients with thymic T-cell malignancies not only have distinctive biologic characteristics to their blasts, but also have a distinctive pattern of clinical presentation, response to therapy, and sites of relapse. These differences have prompted the search for specific therapies and also directed approaches to understanding the variable clinical outcome of patients with these malignancies.