Identification of two major B cell forms of nodular mixed lymphoma

To resolve the controversy over the immunologic nature of nodular mixed lymphoma (NM), we examined nine cases of NM for surface antigens using both tissue section and cell suspension methods. These were contrasted with 12 cases of nodular poorly differentiated lymphocytic lymphoma. We found two major B cell types of NM, those with monoclonal immunoglobulin (SIg+)-positive nodules with an SIg+B1+B2+Ia+T- phenotype (four cases) and those with nodules devoid of immunoglobulin with an SIg-B1+B2-Ia+T- phenotype (five cases). Our SIg+ NM cases appear similar to nodular poorly differentiated lymphocytic lymphoma (SIg+B1+B2+Ia+T-), except suspension assay indicates fewer SIg+ cells in NM. In our SIg- NM cases, the neoplastic nodules consistently expressed B1 and Ia-like antigens and lacked T cells, indicating a B cell neoplasm similar to many large cell lymphomas. By demonstrating a B cell antigen in SIg- nodules, we substantially resolve the controversial NM cases previously called "null" or T cell. The two distinct immunotypes indicate the complexity of B cell antigenic expression in NM and might also explain the variable response to therapy in NM described in previous studies. Finally, we describe NM cases with the simultaneous occurrence of several stages of B cell differentiation. This suggests that some NM cases are not frozen in a single stage of B cell development but may express a range of B cell antigens. NM, then, may be a paradigm of variable, simultaneous B cell maturation.