Diffuse Low-Grade B-Cell Lymphomas:<i>Four Clinically Distinct Subtypes Defined by a Combination of Morphologic and Immunophenotypic Features</i>

Zukerberg, Lawrence; Medeiros, L. Jeffery; Ferry, Judith A.; Harris, Nancy L.

doi:10.1093/ajcp/100.4.373

Cited by 126 publications

(59 citation statements)

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“…28 Expression of cyclin D1 has also been observed in cases of multiple lymphomatous polyposis (Figure 1), the intestinal form of mantle cell lymphoma. 11 Cyclin D1 expression is not completely specific for mantle cell lymphoma 29,30 : it has been found in plasmacytoma/myeloma, especially in cases with t(11;14) 31,32 ; in sporadic cases of B-cell chronic lymphocytic leukemia (B-CLL), some of which show t (11;14) and CCND1 rearrangement, 33 and in hairy cell leukemia, although levels of cyclin D1 are lower than in mantle cell lymphoma and no CCND1 (BCL-1) gene rearrangements are detected. 33,34 Expression of CCND1 (BCL-1) mRNA due to t (11; 14) has been found in some cases of splenic marginal zone lymphoma, 13 but no protein has been detected by immunohistological methods in this disease.…”

Section: Genes Activated By Chromosomal Changesmentioning

confidence: 99%

Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry

Falini

Mason

2002

Blood

174

147

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IntroductionTranslocations, deletions, and other nonrandom chromosomal abnormalities 1,2 play a central role in the pathogenesis of many human hematologic malignant diseases. A growing number of studies are revealing the ways in which these chromosomal alterations affect specific genes, such as those encoding nuclear transcription factors. However, any gene implicated in the neoplastic process can act only through the protein it encodes. Many of the consequences of chromosomal changes with respect to abnormal protein expression have been inferred indirectly by analysis of messenger RNA (mRNA) transcription, but it is clear that protein and mRNA levels do not always correlate. For example, germinalcenter B cells appear to contain BCL-2 message but little protein, 3,4 and the same is true for TAL-1 in erythroid cells. 5 Many examples of the opposite combination (high protein and little or no message) also exist, such as BCL-2 in mature lymphocytes 6,7 and elastase in mature myeloid cells. 8 Antibody-based detection of the protein is therefore required, but this frequently cannot be done because of a lack of suitable reagents. Consequently, we are often ignorant not only about patterns of expression of oncogenic proteins in hematologic neoplasms but also about possible abnormalities in the distribution and subcellular localization of these proteins.Most of the currently recognized genetic alterations in human leukemias and lymphomas result in either activation of a quiescent gene or creation of a hybrid gene encoding a chimeric protein. Table 1 summarizes the genetic abnormalities that have been studied using antibodies specific for the protein products of genes involved in such rearrangements. We here review the immunocytochemical studies that have been done with these antibodies and assess, for each protein, whether abnormalities demonstrable by immunocytochemistry are of clinical value in determining diagnosis or predicting prognosis. Immunocytochemical findings that are of value are discussed below, whereas those for which no clear clinical applications have been observed are described briefly in Table 2. Genes activated by chromosomal changesThe CCND1 (BCL-1) gene and its protein product (cyclin D1) CCND1 (BCL-1) gene. The (11;14)(q13;q32) translocation, 9 an anomaly often found in mantle cell (centrocytic) lymphoma 10,11 and occasionally in other B-cell neoplasms, notably myeloma, 12,13 From For personal use only. on May 12, 2018. by guest www.bloodjournal.org From juxtaposes the CCND1 (BCL-1) locus encoding cyclin D1 on chromosome 11 to an immunoglobulin-enhancer sequence on chromosome 14. 9 The CCND1 gene is transcriptionally silent in normal lymphohemopoietic tissues 14,15 ; thus, expression of the protein may promote neoplastic cell proliferation by perpetuating the transition from G 1 to S. 16 Antibodies to cyclin D1. Several antibodies recognizing cyclin D1 have been described (Table 3), [14][15][16][17][18] but hematopathologists know that immunocytochemical detection of cyclin D1 in routinely processe...

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Section: Genes Activated By Chromosomal Changesmentioning

confidence: 99%

Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry

Falini

Mason

2002

Blood

174

147

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“…34 Previously undetected monoclonal B cell malignancies were discovered in two of the pancytopenic patients studied by use of the MDF screening with subsequent appropriate immunophenotypic panels that delineate and classify non-Hodgkin's lymphomas. 22,[35][36][37][38] It should be emphasized that small clonal B cell populations incidentally detected by flow cytometry at low percentages may not have clinical significance, but patients should be followed over time to rule out frank nonHodgkin's lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias

Wells¹,

Hall²,

Shulman

et al. 1998

Leukemia

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Patients with unexplained cytopenias often present a diagnostic dilemma with minimal morphologic or cytogenetic changes to identify the underlying disease process. We have used multidimensional flow cytometry in a study of patients with cytopenias and found that this technology established, changed, or refined the diagnosis in 17/121 patients. Using the flow cytometric technique of CD45 and right angle light scatter (SSC) gating with two additional markers in a three-color analysis, eight of 121 patients were found to have hairy cell leukemia (HCL), in the absence of definitive morphologic findings of HCL. Two additional patients were found to have non-Hodgkin's lymphoma (NHL). Myeloid abnormalities, myelodysplasia (MDS) or acute leukemia was detected in seven of 56 patients with unexplained pancytopenia. Six of 65 patients identified with cytopenias resulting from lymphoid neoplasms had been referred for bone marrow transplantation (BMT) with a presumptive diagnosis of MDS, with subsequent deferral of BMT upon correct diagnosis. The screening technique is incorporated into an extensive immunophenotyping scheme to identify hematopoietic abnormalities using multidimensional flow cytometry (MDF). HCL cells (detected as low as 1.3%) reside in the same position as normal monocytes in the CD45 and SSC plots but could be distinguished from monocytes based on the expression of HLA-DR without CD11b, and expression of CD19. Further phenotyping of the abnormal population confirmed immunoglobulin light chain restriction, CD11c, and CD25 expression. Non-Hodgkin's lymphoma was detected as aberrant mature lymphocytes expressing B lymphoid markers, CD5 and light chain restriction. Myeloid abnormalities were identified in the myeloblast or maturing myeloid cell fractions. The flow cytometric scheme described can be used in primary diagnosis. The technique is definitive, sensitive, and stresses the importance of distinguishing lymphoid from myeloid etiology of cytopenias.

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“…Malignant cells are negative for CD10, CD23 and BCL6. Although absence of CD23 antigen expression on malignant cell population strongly favor a diagnosis of MCL 12,13 , presence of cyclinD1 expression by immunohistochemical staining 14 or determination of t (11;14) translocation by molecular analysis [15][16][17][18] is required to confirm the diagnosis 19 . Cyclin D1 is overexpressed in MCL as a result of the landmark t(11;14)(q13;q32) translocation 20 .…”

Section: Diagnosismentioning

confidence: 99%

Mantle Cell Lymphoma: Decision Making for Transplant

Koç¹,

Demirer²

2012

New Advances in Stem Cell Transplantation

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Diffuse Low-Grade B-Cell Lymphomas:Four Clinically Distinct Subtypes Defined by a Combination of Morphologic and Immunophenotypic Features

Cited by 126 publications

References 0 publications

Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry

Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry

Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias

Mantle Cell Lymphoma: Decision Making for Transplant

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