The World Health Organization (WHO) classification of lymphoid neoplasms has gained worldwide acceptance by both pathologists and oncologists. As further advances in the classification of lymphoma are agreed upon, the WHO provides an updated version of its classification. The most recent modification was published in 2016. It provides a list of distinct lymphocytic neoplasms that are defined by a combination of morphologic, immunophenotypic, genetic, and clinical features and correlates each disease with a cell of origin in the lymphopoietic hierarchy. Because the classification of lymphomas requires the integration of such diverse information, the diagnosis of specific lymphomas has become more complex compared to other malignancies. As a result, several ancillary studies have become essential in the diagnosis of a specific pathological type of lymphoma, requiring special handling of biopsy material when a diagnosis of lymphoma is suspected. The WHO classification identifies three major categories of lymphoid malignancies: B-cell neoplasms, T- and natural-killer (NK) cell neoplasms, and Hodgkin lymphoma. Two major categories are identified within the B-cell and T-/NK-cell neoplasms: precursor neoplasms and peripheral or mature neoplasms. Unlike previous lymphoma classifications, the WHO classification does not group different lymphomas by clinical outcome or histologic grade. It recognizes that each disease has distinctive clinical features and response to treatment and may have a spectrum of rate of clinical progression that may correlate with histologic grade or gene expression patterns. New approaches for classifying lymphoma include the study of gene expression profiling by complementary DNA microarray technology, which provides additional insights into the subclassification of diseases such as diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Proteomic approaches will add further texture to the molecular taxonomy of lymphoma classification.
HISTORICAL ASPECTS OF LYMPHOMA CLASSIFICATION
The classification of malignant lymphoma had been fraught with controversy during much of the 20th century, but consensus has been reached during the past two decades. A detailed discussion of the history of lymphoma classification is beyond the scope of this chapter and can be found elsewhere.1,1a
Acronyms and Abbreviations:
ABC, activated B cell; ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; FISH, fluorescence in situ hybridization; GCB, germinal center B cell; IGH, immunoglobulin heavy chain; LP, lymphocyte predominant; MALT, mucosa-associated lymphoid tissue; NF-κB, nuclear factor-κB; NK, natural killer; PCR, polymerase chain reaction; PTCL, peripheral T-cell lymphoma; REAL, Revised European-American Lymphoma; WHO, World Health Organization; ZAP-70, zeta-associated protein of 70 kDa.
From Thomas Hodgkin’s description in 1832 of what became known as Hodgkin disease2 to the first half of the 20th century, several types of lymphomas with distinctive morphologic and clinical features were described using a variety of terms, including lymphoma, lymphosarcoma, reticulum cell sarcoma, and giant follicular lymphoma.1,1a However, many of the terms were not used uniformly, resulting in significant misunderstanding, particularly between pathologists ...