Monoclonal B-Cell Lymphocytosis Exhibiting Immunophenotypic Features Consistent with Marginal Zone Origin: What Is This Entity?

Abstract Abstract 1587 Monoclonal B-cell lymphocytosis (MBL) with an immunophenotype consistent with marginal zone origin (MBL-MZ), that can be either CD5− or CD5+ but atypical for CLL, and also lacking an IGH/CCND1 translocation, is an increasingly recognised entity with poorly understood biological background and clinical significance. In particular, it is not yet clarified whether it represents a precursor state to one of the distinct lymphoma entities recognized by WHO as deriving from MZ cells or whether it constitutes a novel entity, likely with similar ontogeny. To obtain insight into this issue we retrospectively evaluated a series of 71 patients (male/female: 35/36, median age: 73.3 years) with lymphocytosis (median lymphocyte count: 5.77 × 109/l) detected incidentally on a routine blood test. No case had lymphadenopathy, organomegaly or any clinical features to suggest a concurrent marginal zone lymphoma. Hemoglobin and platelet counts were normal in all cases; 15/57 (26%) cases had paraproteinemia. Peripheral blood immunophenotyping revealed the presence of a clonal B-cell population with Matutes score <2 in all cases. Individual markers were expressed as follows: CD5: 15/71, CD23: 7/70, CD79β: 60/64, FMC7: 50/67, CD49d: 35/35, CD38: 6/53. In 8/45 cases assessed with CT-scan and/or ultrasound, borderline splenomegaly was observed. Histopathological examination of the bone marrow biopsy (BMB) was available in 11 cases and demonstrated mostly mixed patterns of neoplastic lymphocytic inflitration from small B cells. Karyotype data were available in 66 cases; 48/66 (72.7%) had abnormal karyotype. Main cytogenetic findings are as follows: (1) translocations: n=16 cases of which 3 carried t(2;7)(p11;q21/22); (2) isochromosome 17q: n=8; (3) trisomy 12: n=8; (4) del(7q): n=7; (5) trisomy 3: n=4. Immunogenetic analysis revealed overusage of the IGHV4–34 gene (15/63, 23.8%). Notably, the IGHV1–2 gene was utilized by a single case, thus sharply contrasting (p<0.0001) splenic marginal-zone lymphoma (SMZL) with a reported frequency of IGHV1–2 in excess of 30%. Seven of 63 rearrangements (11.1%) carried IGHV genes with no somatic mutations, whereas the remainder (56/63, 88.9%) exhibited some impact of somatic hypermutation (SHM), ranging from minimal to (mostly) pronounced. Overall, cases of the present study exhibited a significantly (p<0.005) higher SHM load compared to SMZL. With a median follow-up of 4.9 years (0.8–20), 54 cases (group A) remain stable with no signs of progression. The remaining 17 cases (group B) have MBL along with clinical or histopathologic evidence of lymphoma. In particular: (i) a female with MBL as an incidental finding, also carrying t(2;7), was eventually diagnosed with gastric MALT lymphoma at +11 months from presentation; immunogenetic analysis confirmed clonal identity between the MBL and the lymphoma; (ii) 2 cases developed lymphadenopathy; (iii) a single case developed diffuse large B cell lymphoma of the skin; and, (iv) 13 cases developed splenomegaly and, thus, can be considered as either SMZL or splenic lymphoma/leukemia unclassifiable (SLLU). Groups A and B did not differ in terms of demographics, diagnostic blood counts (including clonal MBL count) and SHM status; the only difference concerned cytogenetic profiles, with i(17)(q10) and del(7q) being almost exclusive to group A. In conclusion, we demonstrate that MBL-MZ can be the presenting feature of occult MZ lymphoma, most frequently SMZL/SLLU. However, in a sizeable proportion of cases, MBL-MZ remains stable over time with no evidence of organ involvement and distinct immunogenetic features from SMZL, thereby raising the possibility that it might represent a newcomer to the spectrum of B-cell lymphoproliferations of MZ origin. Disclosures: No relevant conflicts of interest to declare.

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Splenic Marginal Zone Lymphoma Shows a Distinct Pattern of DNA Copy Number Aberrations That Correlates with Tumor Characteristics and Predicts Disease Outcome.

Blood ◽

10.1182/blood.v108.11.2422.2422 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2422-2422

Author(s):

Jose A. Martinez-Climent ◽

Cristina Robledo ◽

Manuela Mollejo ◽

Anton Parker ◽

Juan L. Garcia ◽

...

Keyword(s):

B Cell ◽

Copy Number ◽

Marginal Zone ◽

Array Cgh ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma ◽

Genomic Aberrations ◽

7Q Deletion

Abstract Splenic marginal zone lymphoma (SMZL) is an indolent B cell malignancy whose diagnosis is based on lymphocyte morphology, immunophenotype and marrow and/or splenic histology. Unlike other lymphomas, there is not a common chromosomal translocation specific for SMZL, and genetic prognostic factors are poorly defined. To investigate the pattern of genomic aberrations in SMZL, we applied comparative genomic hybridization to BAC microarrays (array CGH) to a well characterized series of 75 SMZL specimens. We applied two different 1 Mb-resolution BAC arrays: UCSF HumArray 3.2 and a novel array CGH platform developed at Univ. of Salamanca. These arrays allowed us to detect DNA copy number changes across the genome with high accuracy in 67 of 75 patient samples. Data were compared with our previous array CGH studies of 170 samples from different B-cell lymphoma subgroups. FISH studies for IGH, IGK and IGL translocations and 7q deletion were performed on tissue microarrays in 24 cases. Of the 67 samples, 19 (28%) showed a normal genomic profile. The median number of genomic aberrations per tumor was 2.2 (1.3 gains and 0.9 losses), which was lower than the rates detected in other lymphoma subgroups (diffuse large cell lymphoma, 6.4; mantle cell lymphoma, 6; follicular lymphoma, 4.5) and comparable to MALT lymphomas (2 abnormalities per tumor). SMZL cells showed a genomic pattern characterized by gain of chromosomes 3q24-q29 (18%), 6p (9%), 12q (9%), and 18q (4%) and loss of 7q32 (34%), 8p21-p23 (13%), 17p13 (10%) at P53 locus and 6q21-q27 (9%). Notably, no alterations of the P16/ARF (9p21) or MYC loci (8q24) were detected. Correlation of array CGH data with conventional cytogenetics, FISH and LOH studies revealed a high concordance. Detailed mapping of 7q deletions delineated a consensus region of loss of 3 Mb in 7q32. This 7q deletion was almost exclusive to SMZL, being observed in only 5 of 170 non-SMZL B-cell lymphomas (p=0.0000001). Four cases presented IG-translocation. Mutation of IGH was observed in 62% and correlated with a complex karyotype (61 vs. 13%; p=0,0008) whereas unmutated IGH correlated with the deletion of 7q (56 vs. 23%; p=0,01). Among the various genomic abnormalities, only the deletion of 8p or the presence of a complex karyotype correlated with inferior overall survival (OS) (median OS, 58 vs. 110 months, p=0,004; and 60 vs. 105 months, p=0,01; respectively). In summary, array CGH has defined a pattern of genomic aberrations in SMZL that differs from other B-cell lymphoma subgroups and that may predict overall survival. Because the deletion of 7q32 is the most distinctive genetic marker in SMZL, the identification of a putative tumor suppressor gene inactivated within the region of deletion seems mandatory.

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Absence of Mutations of the Histone Methyltransferase Gene EZH2 In Splenic B-Cell Marginal Zone Lymphoma

Blood ◽

10.1182/blood.v116.21.5086.5086 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5086-5086

Author(s):

Luz Martínez-Avilés ◽

Marta Salido ◽

Beatriz Bellosillo ◽

Vera Adema ◽

Ana Ferrer ◽

...

Keyword(s):

B Cell ◽

Marginal Zone ◽

Mutational Analysis ◽

Conflicts Of Interest ◽

Direct Sequencing ◽

Normal Karyotype ◽

Marginal Zone Lymphoma ◽

Low Grade ◽

Splenic Marginal Zone Lymphoma ◽

7Q Deletion

Abstract Abstract 5086 Background Splenic marginal zone lymphoma (SMZL) is a rare low-grade B-cell lymphoproliferative disorder with characteristic clinical, cytological, histological and immunophenotypical features. The most common cytogenetic abnormality, present in 30–40% of the patients is the 7q deletion, that extends from 7q21 to 7q36. This aberration may represent a primary pathogenic event in SMZL. Recently, mutations in the EZH2 gene, located at 7q36.1, have been described in different hematological malignancies including B-cell lymphomas. However, the role of the EZH2 gene in SMZL has to be elucidated. Aim To determine the prevalence of EZH2 mutations in a cohort of SMZL patients. Patients and Methods Twenty-nine patients with SMZL were screened for mutations in the EZH2 gene. From the whole cohort, 11 patients presented 7q deletion (three of them as a single anomaly), 11 had a normal karyotype and 7 had other cytogenetic aberrations. The mutational analysis of the EZH2 gene was performed by direct sequencing using primers covering the whole exome of the gene. DNA was extracted from CD19 isolated B-cells from peripheral blood or from total lymphocytes if the percentage of pathologic B-cell was higher than 50%. Results From the whole cohort of 29 SMZL patients, no pathogenic mutations (frameshift or nonsense mutations) were detected in the EZH2 gene in any of the patients analyzed. Five patients harboured the missense mutation D185H in exon 6, that has been previously described as a single nucleotide polymorphism (SNP). Conclusions In conclusion, the EZH2 gene is not mutated in our series of SMZL patients suggesting that this gene is not involved in the pathogeny of this entity. Acknowledgments: Fellowship FI2008 (AGAUR) to LMA, This work was supported (in part) by grants from Instituto de Salud Carlos III FEDER; Red Temática de Investigación Cooperativa en Cáncer (RTICC, FEDER): RD06/0020/0031 and RD07/0020/2004; Ministerio de Sanidad y Consumo (Spain): PI07/0586. Disclosures: No relevant conflicts of interest to declare.

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Splenectomy Is Still a Valid Option For Splenic Marginal Zone Lymphoma

Blood ◽

10.1182/blood.v122.21.5129.5129 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5129-5129

Author(s):

Alessandro Pulsoni ◽

Pasqualina D'Urso ◽

Gianna Maria D'Elia ◽

Giorgia Annechini ◽

Caterina Stefanizzi ◽

...

Keyword(s):

Marginal Zone ◽

Conflicts Of Interest ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma ◽

Spleen Size ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma characterized by splenomegaly, frequent moderate lymphocytosis with or without villous morphology and possible involvement of various organs, especially the bone marrow (BM). Diagnosis is classically based on the spleen histology, but it can be made on the BM biopsy, based on the typical intrasinusoidal cell infiltration pattern and immunohistochemistry. Different therapeutic options are available, but to date there are no conclusive comparative data. Patients and methods We retrospectively analyzed 83 consecutive patients with a diagnosis of SMZL observed at our Institution between 1999 and 2013. The diagnosis was based on the BM biopsy in 79 patients; the BM was negative in 4 patients. Diagnosis was histologically confirmed on the spleen in 27 patients who underwent splenectomy. Patients presented a median age of 72.5 years (range 38-84); 43 were males. The median spleen size at diagnosis was 145 mm, ranging from 100 to 300 mm. The majority of patients were stage IV at diagnosis for BM infiltration (95%); B symptoms were present in 4 of them (4.8%). Forty-two patients (50.6%) had a lymphocytosis at diagnosis and 13 (15.6%) presented an IPI score higher than 3. Thirty-five of them (42%) had a MZL BM infiltration superior to 30% of the total bone cellularity. Forty-two patients (50.6%) underwent a watch and wait policy (WW), while 41 (49.4%) were treated within 6 months from diagnosis, mainly because of symptomatic splenomegaly; in these patients, treatment consisted of splenectomy, chemotherapy or chemotherapy plus immunotherapy with Rituximab. The features of patients submitted to WW with respect to patients treated at diagnosis were comparable for the various parameters mentioned above, except for spleen size (higher in patients treated at presentation) and lymphocyte count (higher in patients who were observed). After a median follow-up of 64 months, the overall median survival was 96%. Among the 42 WW patients, 18 (42.8%) are still untreated after a median follow-up of 57.5 months, while 24 (57.2%) have required therapy; the median treatment-free interval in these patients was 25.5 months. Concerning the 41 patients who underwent treatment at diagnosis, after a median follow-up of 50 months, 13 (31.7%) have required a subsequent second-line treatment. The interval between first-line approach and re-treatment in patients treated at diagnosis was 30 months. Overall, 27 patients were treated with splenectomy only (either at diagnosis or after a WW period): only 6 of them (22%) had a subsequent progression after a median latency of 42 months; 26 were treated with chemotherapy alone (alkylating agents in the majority of them, combination therapy in a minority): 15 of them (60%) had a subsequent relapse or progression after a median of 9 months; 12 patients received a Rituximab-containing regimen: of these, only 2 (16%) have so far required a second-line therapy after 10 and 26 months respectively. Conclusions The WW policy is a valid option for asymptomatic patients: in these patients, after 4.5 years from diagnosis more than 40% is still untreated. In patients requiring treatment, splenectomy alone is followed in the majority of patients by a long period of good disease control: only 22% required a second-line therapy after 3.5 years. The addiction of Rituximab to chemotherapy seems to reduce the probability of relapse and to prolong the response duration. However, these preliminary data need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.

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Grey zone lymphoid neoplasms with features overlapping between splenic marginal zone lymphoma and hairy cell leukaemia: splenic B-cell lymphoma/leukaemia, unclassifiable

Journal of Hematopathology ◽

10.1007/s12308-011-0092-x ◽

2011 ◽

Vol 4 (2) ◽

pp. 93-100 ◽

Cited By ~ 1

Author(s):

Kikkeri N. Naresh

Keyword(s):

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Hairy Cell Leukaemia ◽

Cell Leukaemia ◽

Splenic Marginal Zone Lymphoma ◽

Grey Zone ◽

Hairy Cell

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Deregulated PAX-5 Transcription From a TranslocatedIgH Promoter in Marginal Zone Lymphoma

Blood ◽

10.1182/blood.v92.10.3865 ◽

1998 ◽

Vol 92 (10) ◽

pp. 3865-3878 ◽

Cited By ~ 62

Author(s):

Aline M. Morrison ◽

Ulrich Jäger ◽

Andreas Chott ◽

Michael Schebesta ◽

Oskar A. Haas ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Marginal Zone ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Chain Gene ◽

Splenic Marginal Zone Lymphoma ◽

Derivative Chromosome ◽

B Cell Differentiation ◽

Loss Of Function

Abstract The PAX-5 gene codes for the transcription factor BSAP, which is expressed throughout B-cell development. Although loss-of-function mutation in the mouse showed an essential role forPax-5 in early B lymphopoiesis, gain-of-function mutations have implicated the human PAX-5 gene in the control of late B-cell differentiation. PAX-5 (on 9p13) has been involved together with the immunoglobulin heavy-chain (IgH) gene (on 14q32) in the recurring t(9;14)(p13;q32) translocation that is characteristic of small lymphocytic lymphoma with plasmacytoid differentiation. Here we have characterized a complex t(2;9;14)(p12;p13;q32) translocation present in a closely related non-Hodgkin’s lymphoma referred to as splenic marginal zone lymphoma (MZL). In this MZL-1 translocation, the two promoters of PAX-5 were replaced on the derivative chromosome 14 by an immunoglobulin switch Sμ promoter that was linked to the structural PAX-5 gene upstream of its translation initiation codon in exon 1B. Expression analyses confirmed thatPAX-5 transcription was upregulated due to efficient initiation at the Sμ promoter in the malignant B lymphocytes of patient MZL-1. For comparison we have analyzed PAX-5 expression in another B-cell lymphoma, KIS-1, indicating that transcription from the distalPAX-5 promoter was increased in this tumor in agreement with the previously characterized translocation of the immunoglobulin Eμ enhancer adjacent to PAX-5 exon 1A. In both lymphomas, the J-chain gene, which is thought to be under negative control by BSAP, was not expressed, whereas transcription of the putative target genep53 was unaffected by PAX-5 overexpression. Together these data indicate that the t(9;14)(p13;q32) translocation contributes to lymphoma formation as a regulatory mutation that leads to increasedPAX-5 expression in late B-cell differentiation due to promoter replacement or enhancer insertion.

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The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v95.2.627 ◽

2000 ◽

Vol 95 (2) ◽

pp. 627-632 ◽

Cited By ~ 135

Author(s):

Dan Jones ◽

Richard J. Benjamin ◽

Aliakbar Shahsafaei ◽

David M. Dorfman

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Chemokine Receptor ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Lymphocytic Leukemia ◽

Splenic Marginal Zone Lymphoma ◽

Flow Cytometric

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell–associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas.

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Gene Expression Profiling of Post-Follicular B-Cell Lymphoma

Blood ◽

10.1182/blood.v112.11.617.617 ◽

2008 ◽

Vol 112 (11) ◽

pp. 617-617

Author(s):

Wee-Joo Chng ◽

Gaofeng Huang ◽

Paul J. Kurtin ◽

Ahmet Dogan ◽

Ellen Remstein

Keyword(s):

Gene Expression ◽

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Gene Set Enrichment Analysis ◽

Splenic Marginal Zone Lymphoma ◽

Major Cluster ◽

Significant Enrichment

Abstract Although classified as marginal zone lymphomas under the WHO classification, the molecular relationship between splenic marginal zone lymphoma (SMZL), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), and nodal marginal zone lymphoma (NMZL) has not been clarified. Furthermore, lymphoplasmacytic lymphoma (LPL) can show clinical morphologic and immunophenotypic overlap with these entities and may present a diagnostic challenge. In this analysis of gene expression data generated using the Affymetrix U133plus 2.0 chip from 32 SMZL, 25 MALTs (GI, salivary gland and lung), 23 NMZL and 25 LPL, we aim to identify the molecular relationship between these pathological entities using unsupervised methods, identify disease specific signatures and markers using supervised methods and also the functional implications of these signatures using a modified gene-set enrichment analysis. Using hierarchical clustering, MALT lymphoma forms a tight cluster regardless of tumor site. In addition, SMZL and NMZL form another large cluster. LPLs are divided into 2 main clusters with occasional samples interspersed amongst the SMZL and NMZL. There is no correlation between the percentage of CD20-positive B-cells, CD3-positive T-cells or CD138- positive plasma cells or tissue origin of the tumor and the way the samples are clustered. However, the separation of the LPLs into 2 major cluster correspond to the presence and absence of underlying Waldenstrom Macroglobulinaemia (WM), suggesting that the genes distinguishing the 2 clusters are potential markers for differentiating WM LPL from non-WM LPL. Next, using supervised analysis we identified a cluster of genes including MMP7, LTF and SFRP2 with high signals specific to MALTs, while other genes including PRDM1 (BLIMP1), XBP1 and TNFRSF17 (BCMA) were specifically over-expressed in LPL. These may therefore represent novel diagnostic marker differentiating these entities. Several of these are further validated at the protein level using immunohistochemistry on a tissue microarray. Consistent with the unsupervised analysis, SMZL and NMZL have little difference and share the over-expression of CD22 and WNT3 among other genes. Clustering of these samples based on the pathways and genesets that are enriched in the individual tumors as compared to their normal tissue counterpart showed a mutually exclusive pattern with significant enrichment of NFKB-related genesets and genes in LPL and MALT, and significant enrichment of B-cell receptor signaling genesets and genes in SMZL and NMZL. Our analysis, for the first time, describes the molecular relationship between these closely related lymphomas. In the process, we identified novel diagnostic markers that may differentiate these conditions and also new insights into molecular pathways that are differentially activated in the different conditions. These may represent potential therapeutic targets

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Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma

Blood ◽

10.1182/blood-2011-06-359166 ◽

2011 ◽

Vol 118 (18) ◽

pp. 4930-4934 ◽

Cited By ~ 124

Author(s):

Davide Rossi ◽

Silvia Deaglio ◽

David Dominguez-Sola ◽

Silvia Rasi ◽

Tiziana Vaisitti ◽

...

Keyword(s):

B Cell ◽

Somatic Mutations ◽

Marginal Zone ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Common Mechanism ◽

Splenic Marginal Zone Lymphoma ◽

Therapeutic Approaches ◽

Molecular Alterations ◽

Suitable Target

Abstract Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types that remain orphan of molecular lesions in cancer-related genes. Detection of active NF-κB signaling in 14 (58%) of 24 SMZLs prompted the investigation of NF-κB molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-κB genes occurred in 36 (36%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-κB pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-κB in SMZL. BIRC3 inactivation in SMZL recurred because of somatic mutations that disrupted the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18) translocation, which points to BIRC3 disruption as a common mechanism across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-κB provide a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a suitable target for NF-κB therapeutic approaches in this lymphoma.

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CD11b Is Useful in the Diagnosis of Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia, Mixed Chronic Lymphocytic Leukemia, and Prolymphocytic Leukemia.

Blood ◽

10.1182/blood.v104.11.4806.4806 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4806-4806

Author(s):

William Fricke

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Marginal Zone Lymphoma ◽

Lymphocytic Leukemia ◽

Splenic Marginal Zone Lymphoma ◽

Prolymphocytic Leukemia

Abstract CD11b is well known as an integrin, Mac-1, is often complexed with CD18, and is found on monocytes, granulocytes, and natural killer cells. It also serves as a receptor for iC3b. However, its occurrence in B cell chronic lymphoproliferative disorders is not generally recognized and has not been fully evaluated. To address this issue, a series of B cell leukemias and lymphomas referred for primary diagnosis was evaluated for the presence of CD11b. The purpose was to determine the frequency of its expression on these tumors and to evaluate its diagnostic value. Consecutive cases referred for flow cytometry as possible lymphoproliferative disease were analyzed. Included were bone marrow, peripheral blood, and lymph nodes. All cases were diagnosed according to the WHO classification based on immunophenotypic, morphologic, and clinical findings. The morphologic criteria of Melo (1986) and Bennett (1989) were used for classification of chronic lymphocytic leukemia (CLL), CLL/prolymphocytic leukemia (CLL/PLL), mixed CLL, and PLL. Cases identified as not related to chronic lymphocytic leukemia or prolymphocytic leukemia were recorded but not further analyzed. Similarly, lymph node and spleen-based tumors were excluded from the final analysis. CD11b was present on cells from 32 of 123 cases, including occasional follicular lymphoma, (5/35); mantle cell lymphoma, (1/8); diffuse large B cell lymphoma, (3/9); hairy cell leukemia, (3/5); multiple myeloma, (1/2); lymphoplasmacytic lymphoma, (2/2); nodal marginal zone lymphoma, 0/1); and splenic marginal zone lymphoma, (1/1). However, it was most consistently expressed on CLL that contained increased numbers of prolymphocytes or large cells and on PLL. A total of 16 such cases were found. Morphologic assessment showed them to include 8 CLL/PLL, 3 mixed CLL, 4 PLL, and 1 typical CLL. The typical CLL case included both large cells and prolymphocytes but did not have more than 10% PLs. Five of the 16 cases (31%) were negative for CD5, CD23, and CD38 but were positive for FMC-7. In contrast, the other 11 cases were all CD5(+) and CD23(+); 3/11 were positive for CD38; and 5/11 were positive for FMC-7. Forty-five CLLs also were identified during the study, of which 27 had sufficient data for comparison. Twenty-six of the 27 CLLs were morphologically typical. The remaining case was mixed CLL. All of the CLLs were CD11b(−), CD5(+) and CD23(+); 15/43 were CD38(+), and 6/43 were FMC-7(+). The findings show that CD11b is expressed on chronic B cell lymphoproliferative disorders. In particular, it is expressed on almost all CLL cases that contain large cells or prolymphocytes and on PLL. Inclusion of CD11b in routine screening panels of possible chronic B cell leukemiaa will improve diagnosis of these disorders.

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