Immunohistologic cellular phenotypes of lymphoproliferative disorders. Comprehensive evaluation of 564 cases including 257 non-Hodgkin's lymphomas classified by the International Working Formulation

Abstract

The plethora of classifications for non-Hodgkin's lymphomas (NHLs) and controversy regarding the merits of the individual classification schemes has led to the articulation of an International Working Formulation for NHL classification by a working group sponsored by the National Cancer Institute. This classification is based on both architectural and cytologic features and has been shown to have clinical relevance, but it is not an immunologic approach. With the use of frozen sections and both polyclonal and monoclonal antibodies, a comprehensive immunohistologic study was made of 564 biopsy specimens 1) for determination of the utility of the principle of monoclonality in differentiating benign from malignant lymphoproliferative disorders, 2) for definition of the immunohistochemical phenotypes of histologically benign and malignant cellular proliferations, and 3) for evaluation of the immunologic phenotype of 257 non-Hodgkin's lymphomas classified by the International Working Formulation. Two hundred seven "reactive benign" lymphoproliferations demonstrated polyclonal immunostaining. Monoclonal kappa light chain immunostaining was demonstrated in 3 of 4 cases classified as atypical hyperplasia, two of which had coexistent NHL or subsequently developed overt NHL. Frozen tissue sections were found to be essential for demonstration of immunoglobulin and glycoprotein membrane antigens. The results of immunohistochemical studies were readily integrated with the International Formulation. Although diffuse mixed and small lymphocytic lymphomas were immunologically heterogeneous (both T- and B-cell), follicular lymphomas were invariably of B-cell type, and immunoblastic lymphomas originating from homogeneous T- and B-cell populations were identified.