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Highly sensitive flow cytometry studies may incidentally identify B cell clones when used to assess plasma cell clonality in bone marrows. Clinical history, which can help differentiate related clones (low grade B cell lymphoma with plasmacytic differentiation/LBCL-PD) from unrelated ones (plasma cell proliferative disorder (PCPD) with an unrelated B cell clone), is often unavailable in referred specimens. We sought to identify morphologic or phenotypic features that would help predict the significance of these clones in the absence of history. We included only cases with identical light chain B and plasma cell clones, as determined by 6-color flow cytometry with additional DNA ploidy analysis, in which the relationship between clones could be established by review of medical records. There were 26 cases; 18 were related (14 were Waldenstrom macroglobulinemia) and eight were unrelated (seven multiple myeloma). Features seen exclusively in LBCL-PD include CD19+/CD45+ clonal plasma cell phenotype (66·7%, P = 0·0022) and morphologic features such as paratrabecular bone marrow involvement, increased mast cells, and plasma cells surrounding B-cell nodules. Aneuploidy was identified exclusively in PCPD cases (75%, P = 0·000028). We conclude that CD19+/CD45+ clonal plasma cell phenotype and aneuploidy are useful in distinguishing related clones (LBCL-PD) from unrelated clones (PCPD)., (© 2015 John Wiley & Sons Ltd.)

CD5 positivity in B-cell lymphoproliferative disorders (LPD) is usually considered characteristic of either chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). However, other neoplastic B-LPDs may express CD5, albeit infrequently. In this study we have reviewed the tissue pathology of CD5+ B-LPDs that do not fulfill diagnostic criteria for CLL or MCL on flow cytometric studies of peripheral blood or bone marrow. Our results indicate that although CD5 positivity is most commonly associated with CLL and MCL, a significant minority of cases do not fall into these two categories. Phenotypically unusual CLL, marginal zone lymphoma and lymphoplasmacytic lymphoma were the most common diagnoses in this group of patients. Applying strict flow cytometry criteria, using genetic studies, and deferring to a lymph node/tissue diagnosis in non-classical cases are critical for accurate diagnosis and classification of CD5+ B-cell LPD., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The pathology and clinical course of patients with CD5+ chronic B-cell lymphoproliferative disorders, excluding those that present with typical chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) or mantle cell lymphoma, (i.e. CD5+B-CLPD) are poorly defined., Methods: We studied patients with CD5+B-CLPD to (1) more completely define the clinical features and pathology of CD5+B-CLPD, (2) compare these features to patients presenting with typical CLL, and (3) test the hypothesis that a subset of patients with CD5+B-CLPD could have a unique B-cell malignancy., Results: We identified 229 patients with CD5+B-CLPD. A definitive pathological diagnosis was made in all 61 (27%) CD5+B-CLPD patients with nonbone marrow (BM) biopsy specimens considered adequate for a comprehensive pathological examination. The most common diagnosis among these 61 patients was CLL (44%) followed by the leukemic phase of marginal zone lymphoma (34%), lymphoplasmacytic lymphoma (11%), diffuse large B cell lymphoma (8%), and high-grade B cell lymphoma not otherwise specified (2%). In contrast, among 168 patients without a non-BM tissue biopsy specimen, a specific diagnosis could be made on review of all available data in only 24 (14%) with 144 (86%) remaining "unclassified.", Conclusions: In patients with CD5+B-CLPD, a definitive diagnosis can be made on an adequate non-BM tissue biopsy suggesting that this entity does not include a novel disease. We recommend that all patients with CD5+B-CLPD should have a non-BM tissue biopsy to make a definitive diagnosis prior to initiation of treatment., (© 2010 International Clinical Cytometry Society.)

Purpose: The diagnosis of monoclonal B-cell lymphocytosis (MBL) is used to characterize patients with a circulating population of clonal B cells, a total B-cell count of less than 5 x 10(9)/L, and no other features of a B-cell lymphoproliferative disorder including lymphadenopathy/organomegaly. The natural history of clinically identified MBL is unclear. The goal of this study was to explore the outcome of patients with MBL relative to that of individuals with Rai stage 0 chronic lymphocytic leukemia (CLL)., Patients and Methods: We used hematopathology records to identify a cohort of 631 patients with newly diagnosed MBL or Rai stage 0 CLL. Within this cohort, 302 patients had MBL (B-cell counts of 0.02 to 4.99 x 10(9)/L); 94 patients had Rai stage 0 CLL with an absolute lymphocyte count (ALC) < or = 10 x 10(9)/L; and 219 patients had Rai stage 0 CLL with an ALC more than 10 x 10(9)/L. Data on clinical outcome were abstracted from medical records., Results: The percentage of MBL patients free of treatment at 1, 2, and 5 years was 99%, 98%, and 93%, respectively. B-cell count as a continuous variable (hazard ratio [HR] = 2.9, P = .04) and CD38 status (HR = 10.8, P = .006) predicted time to treatment (TTT) among MBL patients. The likelihood of treatment for MBL patients was lower (HR = 0.32, P = .04) than that of both Rai stage 0 CLL patients with an ALC less than 10 x 10(9)/L (n = 94) and Rai stage 0 CLL patients with an ALC more than 10 x 10(9)/L (n = 219; P = .0003)., Conclusion: Individuals with MBL identified in clinical practice have a low risk for progression at 5 years. Because B-cell count seems to relate to TTT as a continuous variable, additional studies are needed to determine what B-cell count should be used to distinguish between MBL and CLL.

The diagnosis of chronic lymphocytic leukemia (CLL) in asymptomatic patients has historically been based on documenting a characteristic lymphocyte clone and the presence of lymphocytosis. There are minimal data regarding which lymphocyte parameter (absolute lymphocyte count [ALC] or B-cell count) and what threshold should be used for diagnosis. We analyzed the relationship of ALC and B-cell count with clinical outcome in 459 patients with a clonal population of CLL phenotype to determine (1) whether the CLL diagnosis should be based on ALC or B-cell count, (2) what lymphocyte threshold should be used for diagnosis, and (3) whether any lymphocyte count has independent prognostic value after accounting for biologic/molecular prognostic markers. B-cell count and ALC had similar value for predicting treatment-free survival (TFS) and overall survival as continuous variables, but as binary factors, a B-cell threshold of 11 x 10(9)/L best predicted survival. B-cell count remained an independent predictor of TFS after controlling for ZAP-70, IGHV, CD38, or fluorescence in situ hybridization (FISH) results (all P < .001). These analyses support basing the diagnosis of CLL on B-cell count and retaining the size of the B-cell count in the diagnostic criteria. Using clinically relevant criteria to distinguish between monoclonal B-cell lymphocytosis (MBL) and CLL could minimize patient distress caused by labeling asymptomatic people at low risk for adverse clinical consequences as having CLL.

To eliminate overlap with monoclonal B-cell lymphocytosis (MBL), some have proposed basing the diagnosis of chronic lymphocytic leukemia (CLL) on B lymphocyte count rather than absolute lymphocyte count (ALC). Such criteria should be based, in part, on patient outcomes. We evaluated the clinical implications of the proposed re-classification in 112 consecutive, newly diagnosed, Rai stage 0 patients. The new criteria would have changed the diagnosis from CLL to MBL in 47/112 (42%) patients. There was no difference in time to treatment (TTT) between those classified as MBL and CLL under the new criteria. In contrast, CD38 predicted TTT (p=0.02) regardless of the proposed new classification. Molecular characteristics of the leukemic clone are a better predictor of progression than an arbitrary ALC or B lymphocyte count threshold.

Background: Morphologically malignant lymphocytes in the cerebrospinal fluid (CSF) are highly suggestive of central nervous system involvement by lymphoid malignancy. Although flow cytometry is increasingly used to detect a monoclonal B-cell population in the CSF, the significance of this finding in the absence of morphologically identifiable malignant cells is unknown., Methods: We reviewed CSF flow cytometric results in 32 patients studied at a single institution over 5 years and identified patients who had monoclonal B-cells in the CSF. Clinical presentation and course were reviewed., Results: Twelve patients had a monoclonal B-cell population in the CSF, but only three had clinical evidence of malignant CNS disease. Of the other nine patients, 4 had nonmalignant neurologic disease and five had a lymphoproliferative disorder: chronic lymphocytic leukemia (n = 4) and mantle cell lymphoma (n = 1). In patients who had chronic lymphocytic leukemia and mantle cell lymphoma, the monoclonal B-cell population was small and had an immunophenotype identical to that of circulating malignant B cells. None of these nine patients developed clinical evidence of malignant CNS involvement during follow-up., Conclusion: In patients who have indolent B-cell malignancies, the presence of monoclonal B cells in the CSF may not be diagnostic of clinically significant CNS involvement by a lymphoid malignancy., ((c) 2004 Wiley-Liss, Inc.)