Revised European-American Classification Of Lymphoid Neoplasms Research Articles

The revised European-American Classification of Lymphoid Neoplasms (REAL): a preferred approach for the classification of cutaneous lymphomas.

The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification is based on the principle that each type of lymphoma is a distinct disease defined by morphology, immunophenotypic and genetic features, clinical presentation, and course. If either primary or secondary involvement of the skin is a constant factor, this aspect is considered integral to disease definition. Organ-specific classification schemes, such as that proposed by the European Organization for Research and Treatment of Cancer (EORTC) for cutaneous lymphomas, are not required, and indeed may impede the recognition of common features of diseases involving multiple anatomic sites. The use of multiple classification systems is a step backward, and may lead to confusion among hematologists/oncologists and dermatologists. Nevertheless, cutaneous lymphomas in many instances are distinct. Their natural history is often more indolent than nodal lymphomas, and for that reason they often require different therapeutic approaches. We agree with the efforts of the EORTC classification to emphasize the unique clinical aspects of many cutaneous lymphomas, as this recognition is essential for appropriate clinical management. As has been learned for nodal lymphomas, clinical features play an important role in prognosis and should be used in guiding therapy. For cutaneous lymphomas, the presence or absence of systemic spread is particularly important.

Clinicopathological Evaluation of the Revised European-American Classification of Lymphoid Neoplasms (REAL) in Japan

After the publication of a Revised European-American Classification of Lymphoid Neoplasms (REAL classification) in 1994, there have been reports from Europe and America regarding its practical utility and clinical significance. However, no studies have been published from Eastern countries including Japan. It has been well recognized that the distribution of malignant lymphoma in Japan is quite different from that seen in Western countries. In addition, some new entities have also been described in the REAL classification. Therefore, it seems important to examine its practical utility and clinical significance in Japan.Of the 579 cases reviewed, approximately 68% were B-cell non-Hodgkin's lymphoma (NHL) followed by 27 % T-cell lymphomas. Hodgkin's disease (HD) comprised only 5% of all cases, making the ratio of NHL to HD 20.6. The most common type was diffuse large B-cell lymphoma which represented about 37% of all cases. Peripheral T-cell lymphomas, unspecified (PTCL), occurred in 15% whereas marginal zone B-cell lymphoma followed (14.9%). However, follicle center lymphoma (FCL) was less common (4.4%) as has been previously reported. We evaluated the clinical significance of the new REAL classification in 244 cases. International Prognostic Index (IPI) was a powerful predictor of survival (p<0.0001), and the immunophenotype was significant (p<0.05). Furthermore, here, we also attempt to establish a prognostic scheme based on the histologic type. In conclusion, the REAL classification appears to be useful and clinically significant in Japan.

The Revised European-American Classification of Lymphoid Neoplasms (REAL): a new perspective for the classification of cutaneous lymphomas.

Differing classification schemes for malignant lymphomas have been used in Europe and the United States. Attempts to translate between the principle classifications have been unsuccessful and historically it has been difficult to arrive at an unified approach. In addition, many new lymphoma entities have been recognized in recent years that are not delineated in any of the existing classification schemes. To provide a unified international basis for clinical and investigative work in this field, in 1994 the International Lymphoma Study Group (ILSG) proposed a new classification termed Revised European-American Classification of Lymphoid Neoplasms (REAL). This review discusses the REAL classification, especially as it pertains to cutaneous lymphomas, and provides insight into the clinicopathologic features of lymphoproliferative disease involving the skin. The premise of the REAL classification is that a classification scheme should be based on the delineation of disease entities, utilizing pathologic, immunophenotypic, genetic, and clinical features. Therefore, if cutaneous involvement is an integral aspect of any lymphoma subtype, this clinical information is included in the definition of that neoplasm. We conclude that the principles of the REAL classification are applicable to cutaneous lymphomas, as well as lymphomas involving other anatomic sites.

Clinical Analysis of 670 Cases in Two Trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group Subtyped According to the Revised European-American Classification of Lymphoid Neoplasms: A Comparison With the Working Formulation

In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by morphology, phenotype, and cytogenetics in the proposed Revised European-American Classification of Lymphoid Neoplasms (REAL), the clinical relevance of which is still debated. We analyzed 670 NHL cases included in two randomized clinical trials (EORTC 20855 WF-intermediate/high-grade and 20856 WF-low-grade malignancy) with histologic material available for review. Based on hematoxylin-eosin-stained sections, 77% of cases could be subtyped. Immunophenotyping was considered to be mandatory only in diagnosing T-cell lymphoma and anaplastic large-cell lymphoma. Of 522 cases subtyped, 11% were mantle cell lymphoma (MCL), 5% were marginal zone B-cell lymphoma (MZBCL), 46% were follicle center lymphoma, and 32% were diffuse large B-cell lymphoma. Statistical analysis and comparisons between classifications were made only within each trial and treatment group. MCL and MZBCL were characterized by a shorter median survival (3.4 and 4.1 years, respectively) in comparison with low- and intermediate-grade WF groups (> 9.3 and 5.8 years, respectively). In terms of progression-free survival, MCL showed a behavior similar to the low-grade group, with frequent relapses. Follicle center cell lymphomas behaved as low-grade lymphomas as defined by the WF and diffuse large B-cell lymphomas as the WF-intermediate grade group. Because several NHL entities have a clinical behavior of their own, their recognition by the REAL classification offers clinicians additional information that is not obtained when the WF is used.

Multiparametric immunophenotyping of B cells in peripheral blood of healthy adults by flow cytometry.

The investigation of patients suffering from malignant lymphomas of the B-cell type requires flow cytometric immunophenotyping. Several reports described the expression of almost all B lineage antigens on normal and abnormal B lymphocytes. Thus, immunophenotyping of lymphomas must be interpreted in the context of the reference values obtained for healthy control individuals. For this purpose multiparametric flow cytometric analysis offers the unique feature for lymphocyte subset analysis. In the present study B lymphocytes in the peripheral blood of healthy adults were investigated by multiparametric flow cytometric immunophenotyping for the detection of the frequency (in percent) of antigens provided by the revised European-American classification of lymphoid neoplasms (REAL) classification. Thus, 84 healthy adults were investigated and grouped by age (average ages were as follows: group 1, 25.38 years; group 2, 33.86 years; group 3, 44.17 years; group 4, 55.67 years; group 5, 66.67 years). Analysis was done for surface immunoglobulins (kappa and lambda chains of immunoglobulin M [IgM] and IgD) as well as CD10, CD11c, CD23, CD38, CD103, FMC-7, and B-B4. Three-color immunophenotyping was performed for kappa/CD19/CD5, lambda/CD19/CD5, surface IgM/surface IgD/CD19, FMC-7/CD19/CD5, CD103/CD11c/CD19, CD10/CD23/CD19, and CD38/B-B4/CD19 by live gating of CD19+ events (n = 2,000). Although some numerical differences could be obtained for the different groups, statistical differences (P < 0.005) could only be obtained for the CD19+/CD5+ B-cell subset, which was decreased in the elderly patients (group 5). The established two-color and three-color stainings will serve as a basis for future multiparametric immunophenotyping of abnormal lymphocytes (e.g., for patients suffering from non-Hodgkin's lymphoma of the B-cell type).

Immunological and molecular classification of mucosa-associated lymphoid tissue lymphoma.

Malignant B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type is now considered to be a tumor of marginal zone cells of native or, more frequently, acquired MALT. The relationship of MALT lymphoma to the normal counterpart population is acknowledged by the revised European-American classification of lymphoid neoplasms (R.E.A.L.). It fits into the extranodal subtype of marginal zone lymphoma listed as a distinct entity in this recent classification scheme. A typical feature of this lymphoma type is a close lymphocyte-epithelium interaction as reflected by lymphoepithelial lesions. The immunophenotype is characterized by the expression of Sig and B-cell-associated antigens and by the lack of CD5 and CD10. Frequent occurrence of trisomy 3 has been reported. There is now overwhelming evidence that low-grade MALT lymphomas are subject to immunologic drive. In the stomach, the presence of Helicobacter pylori and locally activated T cells appears to be critical for the growth of neoplastic cells. This finding is of clinical significance since the eradication of H. pylori has been shown to reverse low-grade MALT lymphoma.