Evolution of Lymphoma Diagnosis in the Era of Personalized Medicine: A Marriage of Pathology and Genomics for Clinical Practice

The modern taxonomy of disease builds a framework for precision medicine, by which traditional pathologic criteria are integrated with clinical and genomic features to define disease entities. Two of the most common subtypes of lymphoma on a worldwide basis are follicular lymphoma (FL) and diffuse large B-cell lymphoma. Although BCL2 translocation is the signature lesion of most nodal FL, recent studies have identified significant diversity among follicle center-derived lesions. BCL2-negative FL is a genetically heterogeneous disease that occurs in both nodal and extranodal sites. Several distinct entities have been recognized in the pediatric age group, including pediatric-type FL, testicular FL, and interferon regulatory factor 4 (IRF4)-rearranged large B-cell lymphoma. Diffuse large B-cell lymphoma is a family of aggressive B-cell neoplasms with marked variation in pathogenesis and clinical features. Gene expression profiling >20 years ago identified the cell of origin as a key discriminator, but more recently high-throughput sequencing has identified highly varied mutational profiles that point the way in the future toward improvements in targeted therapy and patient outcome.