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Non-Hodgkin's Lymphoma

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Cellular Classification of Adult Non-Hodgkin Lymphoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

A pathologist should be consulted prior to a biopsy because some studies require special preparation of tissue (e.g., frozen tissue). Knowledge of cell surface markers and immunoglobulin and T-cell receptor gene rearrangements may help with diagnostic and therapeutic decisions. The clonal excess of light chain immunoglobulin may differentiate malignant from reactive cells. Since the prognosis and the approach to treatment are influenced by histopathology, outside biopsy specimens should be carefully reviewed by a hematopathologist who is experienced in diagnosing lymphomas. Although lymph node biopsies are recommended whenever possible, sometimes immunophenotypic data are sufficient to allow diagnosis of lymphoma when fine-needle aspiration cytology is preferred.[1,2]

Historically, uniform treatment of patients with non-Hodgkin lymphoma (NHL) has been hampered by the lack of a uniform classification system. In 1982, results of a consensus study were published as the Working Formulation.[3] The Working Formulation combined results from six major classification systems into one classification. This allowed comparison of studies from different institutions and countries. The Rappaport classification, which also follows, is no longer in common use.

Table 1. Historical Classification Systems for Non-Hodgkin Lymphoma

Working Formulation [3]Rappaport Classification
Low grade
A. Small lymphocytic, consistent with chronic lymphocytic leukemia Diffuse lymphocytic, well-differentiated
B. Follicular, predominantly small-cleaved cell Nodular lymphocytic, poorly differentiated
C. Follicular, mixed small-cleaved, and large cell Nodular mixed, lymphocytic, and histiocytic
Intermediate grade
D. Follicular, predominantly large cell Nodular histiocytic
E. Diffuse, small-cleaved cell Diffuse lymphocytic, poorly differentiated
F. Diffuse mixed, small and large cell Diffuse mixed, lymphocytic, and histiocytic
G. Diffuse, large cell, cleaved, or noncleaved cell Diffuse histiocytic
High grade
H. Immunoblastic, large cell Diffuse histiocytic
I. Lymphoblastic, convoluted, or nonconvoluted cell Diffuse lymphoblastic
J. Small noncleaved-cell, Burkitt, or non-Burkitt Diffuse undifferentiated Burkitt or non-Burkitt

As the understanding of NHL has improved and as the histopathologic diagnosis of NHL has become more sophisticated with the use of immunologic and genetic techniques, a number of new pathologic entities have been described.[4] In addition, the understanding and treatment of many of the previously described pathologic subtypes have changed. As a result, the Working Formulation has become outdated and less useful to clinicians and pathologists. Thus, European and American pathologists have proposed a new classification, the Revised European American Lymphoma (REAL) classification.[5,6,7,8] Since 1995, members of the European and American Hematopathology societies have been collaborating on a new World Health Organization (WHO) classification, which represents an updated version of the REAL system.[9,10,11]

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WebMD Public Information from the National Cancer Institute

Last Updated: May 16, 2012
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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