How do you distinguish benign from malignant extranodal small B-cell proliferations?

The diagnostic criteria for malignancy for small B-cell lymphoproliferative disorders in extranodal sites are controversial. However, a multiparameter approach that integrates clinical features, morphologic features, phenotype, and genetics techniques allows for a confident separation of lymphomas from lymphoid hyperplasia in most cases. By morphologic features, formation of a mass, tissue architectural effacement, cellular monomorphism, cytologic atypia, presence of proliferation centers, and plasma cells containing Dutcher bodies are all features of low-grade B-cell lymphomas. Demonstration of immunoglobulin light chain restriction or of an aberrant B-cell phenotype are immunologic features that help to support a malignant diagnosis. Because of technical limitations and ambiguity regarding the significance of small B-cell clones, the roles of the Southern blot analysis and the polymerase chain reaction techniques to demonstrate clonal immunoglobulin gene rearrangements or various chromosomal translocations must be evaluated further as potential criteria for malignancy. As more molecular techniques are applied to low-grade B-cell lymphoproliferative disorders, more of the steps in lymphomagenesis are being defined, and the critical molecular events that predict adverse clinical outcome have yet to be discovered. Therefore, more studies are required to search for additional molecular markers that define adverse outcome so that the number of cases of borderline small B-cell lymphoproliferative disorders can be minimized.