Wyndham H. Wilson, MD, PhD

The classification of diffuse large B-cell lymphoma into three distinct molecular diseases--germinal center B-cell–like subtype, an activated B-cell–like subtype, and a primary mediastinal B-cell lymphoma subtype--has laid the foundation for the development of new agents and novel strategies that target individual subtypes.

Peripheral T-cell lymphomas (PTCLs) are uncommonly encountered malignancies in the United States, and hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and enteropathy-type T-cell lymphoma (ETTCL) are rare subtypes of PTCLs that often present with primarily extranodal disease. Despite the fact that these tumors have distinct clinical and pathologic features, they are often diagnosed after significant delay. The combination of delay in diagnosis with ineffective therapies has resulted in a poor prognosis in most cases. Techniques that identify T-cell receptor gene rearrangements and flow cytometry that can identify characteristic immunophenotypes have guided our understanding of the underlying cell of origin of these rare PTCLs. As knowledge regarding the biology of these lymphomas increases alongside the development of newer therapeutics with novel mechanisms, clinicians must accordingly improve their familiarity with the clinical settings in which these rare malignancies arise as well as the pathologic features that make them unique

Dr. Rosenwald presents a timelyand highly lucid review ofrecent findings in molecularprofiling-a powerful new tool that ishelping to unravel the clinical andbiologic heterogeneity of lymphomas.Although histologic classificationsprovide a framework for the organizationof lymphomas into distinct diseaseentities with shared pathogenesisand clinical behavior, many ofthese entities continue to display significantclinical and diagnostic variability.Molecular profiling representsthe next step in the evolution of lymphomaclassification that has advancedfrom exclusively morphologic to thecurrent World Health Organizationclassification that incorporates immunophenotypeand genetic endpoints.[1] This evolution is the directresult of insights into the molecularpathogenesis of lymphoma, includingthe identification of "hallmark"genetic abnormalities.