The Utility of Flow Cytometric Immunophenotypic Analysis in the Distinction of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia From Mantle Cell Lymphoma

Kilo, Mary N.; Dorfman, David M.

doi:10.1093/ajcp/105.4.451

Cited by 71 publications

(68 citation statements)

References 7 publications

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“…One potential weakness of our study is that, with the exception of 2 t(11;14) FISH negative cases in the derivation cohort, we have made an assumption that CD5 expression is a condicio sine qua non for the diagnosis of MCL. While others have defined MCL on the basis of obligate CD5 expression (12,16,24), there are reasonably extensive data describing CD5 negative MCL with incidence estimates of 10%-30% of MCL (1,15,18,32). There is some suggestion that CD5 expression in MCL may vary between bone marrow disease and MCL found in the peripheral blood (33) or between classical and blastic variants of MCL (2).…”

Section: (9)mentioning

confidence: 99%

“…While the revised CLL score enables the identification of the majority of classical CLL, there remains a grey area of 'atypical CLL' that scores less than 4 on the revised CLL score (10). It has been suggested that absence of the low affinity immunoglobulin E receptor CD23 precludes the diagnosis of CLL and indicates MCL (8,11,12). These data, however, were largely extrapolated from immunohistochemistry on paraffin embedded tissue sections.…”

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confidence: 99%

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A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma

Medd

Clark

Leyden

et al. 2011

Cytometry Part B Clinical

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Background: Both chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are CD5/19 positive. The t(11;14) MCL translocation is identified by fluorescent in situ hybridization (FISH) and can distinguish the two disorders. We attempted to identify flow cytometric and other markers predictive of a positive FISH test.Methods: We examined 100 atypical CLL/MCL cases for demographic, hematological, and cytometric variables, 96 were FISH tested for t(11;14) and four were known MCL.Results: Twenty-two cases were confirmed as MCL. Multivariate analysis identified four variables associated with MCL: Thrombocytopenia (taken as Plt < 150 3 10 9 /L), CD23 negative, CD20 strong, and CD38 positive, with these variables a four-point score was devised. By ROC analysis, the MCL score was superior in differentiating MCL to the Marsden CLL score (AUC 0.95 vs. 0.78). MCL score !2 showed sensitivity 1, specificity 0.66, positive predictive value (PPV) 0.49, and negative predictive value (NPV) 1 for MCL. The score was then prospectively validated on an independent cohort of 44 cases of atypical CLL/MCL. No MCL had a score <3. Validation PPV/NPV of score !3 were 0.5/1. Overall survival in MCL was shorter compared to t(11;14) negative patients (median 3.3 vs. 4.2 years, HR 2.2, 95% CI 0.87-5.5, P 5 0

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Section: (9)mentioning

confidence: 99%

mentioning

confidence: 99%

A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma

Medd

Clark

Leyden

et al. 2011

Cytometry Part B Clinical

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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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“…Multiple accumulated data have shown increased incidence of these aberrant phenotypes in acute leukemias, [14][15][16][17][18][19][20][21] chronic lymphoproliferative disorders 22 and plasma cell dyscrasias, 23,24 which allows for discrimination between healthy cells and pathological cells within a sample. FCIMPT basically performs the following activities.…”

Section: What Information Can Be Provided By Fcimpt On Hm?mentioning

confidence: 99%

Flow cytometric immunophenotyping of hematological malignancies: the way forward in Nigeria

Olaniyi¹

2011

PLMI

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Aim: This review serves to awaken the interest of stakeholders involved in research and management of hematological malignancies (HM) in the efficacy of flow cytometry in the immunophenotypic characterization of leukemias and lymphomas. This well-defined characterization plays a crucial role in diagnosis, classification, prognostic evaluation, and detection of minimal residual disease, in the context of clinical features and morphological diagnosis. Methodology: Relevant literature was retrieved to highlight the principles of operation of flow cytometry, indications and applications, derivable clinical information and clinical relevance, sources of error, and necessary steps towards definitive and specific diagnosis of each HM. Conclusion: Flow cytometric immunophenotyping (FCIMPT) of HM is highly demanding and capital intensive but its usefulness in profiling these exceptionally heterogeneous disorders, and allowing proper classification along the latest WHO classification guidelines, thereby paving the way for targeted therapy and clinical trial-driven management, significantly outweighs the cost, which can be fully recovered if properly managed. In a low-resource setting like Nigeria, limited immunohistochemistry serves to bridge the gap in technological advancement.

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The Utility of Flow Cytometric Immunophenotypic Analysis in the Distinction of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia From Mantle Cell Lymphoma

Cited by 71 publications

References 7 publications

A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma

A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma

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

Flow cytometric immunophenotyping of hematological malignancies: the way forward in Nigeria

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