Search

Abstract Background Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies. Methods We performed genetic and drug screens to identify new synthetic lethal partners to PIs, and validated candidates in PI-sensitive and -resistant MM cells. We also tested best synthetic lethal interactions in other B-cell malignancies, such as mantle cell, Burkitt’s and diffuse large B-cell lymphomas. We evaluated the toxicity of combination treatments in normal peripheral blood mononuclear cells (PBMCs) and bone marrow stromal cells (BMSCs). We confirmed the combo treatment’ synergistic effects ex vivo in primary CD138+ cells from MM patients, and in different MM xenograft models. We exploited RNA-sequencing and Reverse-Phase Protein Arrays (RPPA) to investigate the molecular mechanisms of the synergy. Results We identified lysine (K)-specific demethylase 1 (LSD1) as a top candidate whose inhibition can synergize with CFZ treatment. LSD1 silencing enhanced CFZ sensitivity in both PI-resistant and -sensitive MM cells, resulting in increased tumor cell death. Several LSD1 inhibitors (SP2509, SP2577, and CC-90011) triggered synergistic cytotoxicity in combination with different PIs in MM and other B-cell neoplasms. CFZ/SP2509 treatment exhibited a favorable cytotoxicity profile toward PBMCs and BMSCs. We confirmed the clinical potential of LSD1-proteasome inhibition in primary CD138+ cells of MM patients, and in MM xenograft models, leading to the inhibition of tumor progression. DNA damage response (DDR) and proliferation machinery were the most affected pathways by CFZ/SP2509 combo treatment, responsible for the anti-tumoral effects. Conclusions The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies. Methods: We performed genetic and drug screens to identify new synthetic lethal partners to PIs, and validated candidates in PI-sensitive and -resistant MM cells. We also tested best synthetic lethal interactions in other B-cell malignancies, such as mantle cell, Burkitt's and diffuse large B-cell lymphomas. We evaluated the toxicity of combination treatments in normal peripheral blood mononuclear cells (PBMCs) and bone marrow stromal cells (BMSCs). We confirmed the combo treatment' synergistic effects ex vivo in primary CD138+ cells from MM patients, and in different MM xenograft models. We exploited RNA-sequencing and Reverse-Phase Protein Arrays (RPPA) to investigate the molecular mechanisms of the synergy. Results: We identified lysine (K)-specific demethylase 1 (LSD1) as a top candidate whose inhibition can synergize with CFZ treatment. LSD1 silencing enhanced CFZ sensitivity in both PI-resistant and -sensitive MM cells, resulting in increased tumor cell death. Several LSD1 inhibitors (SP2509, SP2577, and CC-90011) triggered synergistic cytotoxicity in combination with different PIs in MM and other B-cell neoplasms. CFZ/SP2509 treatment exhibited a favorable cytotoxicity profile toward PBMCs and BMSCs. We confirmed the clinical potential of LSD1-proteasome inhibition in primary CD138+ cells of MM patients, and in MM xenograft models, leading to the inhibition of tumor progression. DNA damage response (DDR) and proliferation machinery were the most affected pathways by CFZ/SP2509 combo treatment, responsible for the anti-tumoral effects. Conclusions: The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project. [ABSTRACT FROM AUTHOR]

Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.

Multiparameter flow cytometry data is visually inspected by expert personnel as part of standard clinical disease diagnosis practice. This is a demanding and costly process, and recent research has demonstrated that it is possible to utilize artificial intelligence (AI) algorithms to assist in the interpretive process. Here we report our examination of three previously published machine learning methods for classification of flow cytometry data and apply these to a B-cell neoplasm dataset to obtain predicted disease subtypes. Each of the examined methods classifies samples according to specific disease categories using ungated flow cytometry data. We compare and contrast the three algorithms with respect to their architectures, and we report the multiclass classification accuracies and relative required computation times. Despite different architectures, two of the methods, flowCat and EnsembleCNN, had similarly good accuracies with relatively fast computational times. We note a speed advantage for EnsembleCNN, particularly in the case of addition of training data and retraining of the classifier., (© 2024 International Clinical Cytometry Society.)

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients. [ABSTRACT FROM AUTHOR]

The article offers information on a study related to second-line, subsequent therapy and outcomes for follicular lymphoma (FL) in U.S. Topics discussed include data taken the observational National LymphoCare Study; quarterly observations regarding disease characteristics, subsequent therapies and observed responses; and frequent utilization of rituximab in second and subsequent treatments.

Objectives To increase awareness of potential diagnostic test interference associated with alemtuzumab, which is a therapeutic immunoglobulin G1 κ monoclonal antibody used in hematologic malignancies, autoimmune diseases, and transplant-related disorders. Methods Bone marrow and blood from patients with T-cell prolymphocytic leukemia treated with alemtuzumab were evaluated by flow cytometry. Healthy donor blood was analyzed with or without in vitro treatment with alemtuzumab for comparison. Results Immunophenotypic analysis of bone marrow collected 4 weeks after alemtuzumab treatment demonstrated artifactual surface κ light chain restriction in CD19+ B cells and CD3+ T cells. Similar findings were observed in blood from another patient in a specimen collected 3 days after alemtuzumab treatment. These findings were recapitulated in healthy donor blood incubated with alemtuzumab. Conclusions Alemtuzumab can produce direct interference during flow cytometry analysis, resulting in false-positive evidence of light chain clonality. Clinicians and laboratorians should be cognizant of this risk to avoid misdiagnosis of B-cell neoplasms. [ABSTRACT FROM AUTHOR]

Objectives: To increase awareness of potential diagnostic test interference associated with alemtuzumab, which is a therapeutic immunoglobulin G1 κ monoclonal antibody used in hematologic malignancies, autoimmune diseases, and transplant-related disorders.Methods: Bone marrow and blood from patients with T-cell prolymphocytic leukemia treated with alemtuzumab were evaluated by flow cytometry. Healthy donor blood was analyzed with or without in vitro treatment with alemtuzumab for comparison.Results: Immunophenotypic analysis of bone marrow collected 4 weeks after alemtuzumab treatment demonstrated artifactual surface κ light chain restriction in CD19+ B cells and CD3+ T cells. Similar findings were observed in blood from another patient in a specimen collected 3 days after alemtuzumab treatment. These findings were recapitulated in healthy donor blood incubated with alemtuzumab.Conclusions: Alemtuzumab can produce direct interference during flow cytometry analysis, resulting in false-positive evidence of light chain clonality. Clinicians and laboratorians should be cognizant of this risk to avoid misdiagnosis of B-cell neoplasms. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. METHODS: We analyzed gene expression levels of NF- κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using realtime polymerase chain reaction. RESULTS: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. DISCUSSION AND CONCLUSION: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.

Introduction: Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies., Areas Covered: This article reviews the chemical structure, mechanism of action, and metabolic and toxicological properties of PI3Kδ inhibitors and discusses their clinical applications in monotherapy and in combination with other agents for the treatment of chronic lymphocytic leukemia (CLL). A search was conducted of PubMed, Web of Science, and Google Scholar for articles in English., Results/conclusion: PI3Kδ inhibitors hold potential for the treatment of B-cell malignancies, including CLL. However, their use is also associated with severe toxicities, including pneumonia, cytopenias, hepatitis, and rash. Newer drugs are in development to reduce toxicity with novel schedules and/or combinations., Expert Opinion: The development of novel PI3Kδ inhibitors might help to reduce toxicity and improve efficacy in patients with CLL and other B-cell lymphoid malignancies.

Background: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set.Methods: Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists. The patient characteristics, immunosuppressive regimen, treatment, survival, and follow-up time for 306 cases were extracted from 94 articles, and these cases were combined with 11 cases from Emory University Hospital. Patients with a recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox proportional hazards regression analyses identified predictors of overall survival (OS) for each subtype and B-cell subgroup.Results: OS differed significantly between monomorphic T-cell neoplasms (median, 9 months) and polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median OS was not reached (P = .0001). Significant differences in OS among B subgroups were not detected, but there was a trend toward decreased survival for patients with Burkitt-type PTLD. Kidney transplantation and a reduction of immunosuppression were associated with increased OS for patients with B-cell neoplasms in a multivariate analysis. Immunosuppression with azathioprine was associated with decreased OS for patients with T-cell neoplasms, whereas radiotherapy was associated with improved OS for patients with that subtype.Conclusions: The histologic subtype represents an important prognostic factor in PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower survival for certain subsets of patients with B-cell PTLD should be explored further and suggests the need for subtype-specific therapies to improve outcomes. Cancer 2018;124:2327-36. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Primary non-Hodgkin's lymphoma's of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution.

According to the World Health Organization (WHO) classification, the nosology of B-cell neoplasms integrates clinical, morphological, phenotypic, and genetic data. In this retrospective analysis, we identified 18 patients with isolated neoplastic lymphocytosis that could not be accurately classified within the WHO classification. Most of them were asymptomatic at the time of diagnosis and the evolution was relatively indolent, as only five patients required treatment after a median follow-up of 48 months. The neoplastic B-cells expressed CD5 in most cases, but the Royal Marsden Hospital score was strictly below 3. Trisomy 12 was the most frequent cytogenetic abnormality. High-throughput sequencing highlighted mutations found in both chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL). Similarly, the immunoglobulin heavy chain variable region repertoire was distinct from those reported in CLL or MZL. However, as treatment choice is dependent on the correct classification of the lymphoproliferative disorder, a histological diagnosis should be performed in case patients need to be treated.

A cohort comprising 156 patients with B-cell neoplasms harboring an MYC rearrangement was analyzed with respect to phenotypic presentation, molecular markers ( TP53 , MYC and ID3 ) and additional cytogenetic abnormalities (concomitantly occurring BCL2 , BCL6 and/or CCND1 rearrangements; double, triple or quadruple hit lymphomas = multiple hit lymphomas). MYC translocations occurred as single hit (only MYC rearranged, 63%) or multiple hit lymphoma (37%) and presented as acute leukemia (AL) (14%), Burkitt lymphoma (30%), chronic lymphocytic leukemia (CLL) (21%) or other mature B-cell neoplasms (35%). Multiple hit lymphomas more frequently showed a complex karyotype compared to single hit lymphomas (62% vs. 28%, p < 0.001). Single hit Burkitt lymphomas presented with specific characteristics, by translocation of MYC to an immunoglobulin locus, predominantly a non-complex karyotype (23% vs. 67%, p = 0.012) and a significantly higher ID3 and TP53 mutation frequency ( ID3 mut: 49% vs. 0%, p = 0.002; TP53 mut: 69% vs. 33%, p = 0.045). Additionally, MYC rearranged CLL presented as outstanding group by often showing a non-complex karyotype (85%), absence of ID3 mutations, a high frequency of SF3B1 mutations, and a frequent involvement of non-immunoglobulin loci as MYC- partner genes (61%). Consequently, genetic characteristics distinguish different subgroups of MYC rearranged B-cell neoplasms and therefore may contribute to a new classification system. [ABSTRACT FROM AUTHOR]

Objective: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. Materials and Methods: We analyzed gene expression levels of NFκB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using realtime polymerase chain reaction. Results: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. Conclusion: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions. [ABSTRACT FROM AUTHOR]

Introduction Chronic lymphocytic leukemia is usually diagnosed through the characteristic morphology/immunophenotype of the lymphocytes, but some CLL cases remain atypical resulting in diagnostic uncertainty. Methods Using flow cytometry analysis, we investigated the expression of CDs160/200 on B cells from 124 patients (82 CLL, 42 other B-cell neoplasms) and nine controls. CDs160/200 measurements were determined as a ratio of the mean fluorescence intensities of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively. Results Sixty and 83% CLL expressed CDs160/200 as compared to 5% and 10% of other B-cell neoplasms, respectively. None of the controls showed CDs160/200 expressions. Combination of both markers was observed in 55% of CLL but only in 2% of other B-cell neoplasms, and absence of both markers occurred in 12% of CLL but in 86% of other B-cell neoplasms. Conclusion CDs160/200 were associated with markers of the gold standard 'Matutes score' and could be useful markers to differentiate atypical CLL from other B-cell neoplasms in the absence of available biopsies or cytogenetics and molecular studies. [ABSTRACT FROM AUTHOR]

Objectives: To analyze CD200 expression by flow cytometry in a large series of B-cell neoplasms in a variety of tissue types in comparison with benign B-lineage cells. Methods: We measured CD200 expression levels in 505 peripheral blood (PB), bone marrow (BM), and lymphoid tissue biopsy specimens, including 364 cases positive for B-cell leukemias and lymphomas. Results: CD200 expression in chronic lymphocytic leukemia cases was as bright as or brighter than normal PB B cells in nearly all cases, while mantle cell lymphoma (MCL) cases were usually dim or negative. However, rare MCL cases (about 5%) were moderately bright for CD200. Marginal zone lymphomas varied by subtype, with nodal cases brighter, splenic cases dimmer, and extranodal cases heterogeneous for CD200 expression. Follicular lymphoma (FL) cells were brighter for CD200 in BM specimens than in lymph nodes. In some BM specimens, dim CD200 could distinguish FL cells from background hematogones. Large B-cell lymphomas of the non--germinal center type tended to be brighter for CD200 than those of the germinal center type, while Burkitt lymphomas were negative. Conclusions: CD200 staining by flow cytometry can be useful in the differential diagnosis of B-cell neoplasms and in their detection in the BM. [ABSTRACT FROM AUTHOR]

Hairy cell leukaemia (HCL) is a rare B-cell neoplasm for which the molecular mechanisms are largely unknown. High-density genome-wide DNA profiling was performed with Affymetrix 250K arrays to analyse copy number (CN) changes and loss of heterozygosity (LOH) in 16 cases of HCL. Four of 16 cases (25%) demonstrated gross non-recurrent CN deletions. Within the affected regions, we identified genes involved in bone marrow fibrosis ( FGF12) and response to treatment ( TP53) in individual cases. Large regions (>5 Mb) of LOH without any concomitant DNA CN changes were identified in 5/16 (31%) HCL and were indicative of uniparental disomy UD. The germline origin of UD was demonstrated in one case for which a matched normal sample was available. Overall analysis of LOH showed that identical loci were recurrently targeted in chromosomes 1, 2 and 6. As a whole, however, HCL showed a remarkably stable genome. This finding adds to several other features that are unique to HCL among mature B-cell tumours. [ABSTRACT FROM AUTHOR]

Primary colorectal lymphomas are particularly rare and contribute to 0.2% of all colorectal malignancies. Gastroentrointestinal (GI) tract is most commonly a secondary involvement site for non-Hodgkin’s lymphoma (NHL). Primary NHL of GI tract are very rare, constituting about 1–4% of all GI tract malignancies. In GI tract, two-thirds of all cases occur in stomach followed by small intestine (9%). Clinical presentation depends upon the site of involvement. Pain, loss of appetite, and weight loss are the most common symptoms, while bleeding occurs more with gastric involvement. We present a case of a female presenting as bright red bleed per rectum who was found to have a cecal mass, subsequently diagnosed as extranodal marginal zone B-cell mucosa-associated lymphoid tissue lymphoma with extensive plasma cell differentiation. The diagnosis may be challenging, but a solitary extranodal plasmacytoma and multiple myeloma must be excluded in all such cases. [ABSTRACT FROM AUTHOR]

Aims : To investigate whether an antibody against an intracellular epitope can detect CD19 in routine biopsy specimens and thus to document in detail its expression in human lymphomas. Method and results : A polyclonal antibody to the C terminus of CD19 was used to immunostain paraffin-embedded samples of normal and neoplastic lymphoid tissues. CD19 was widely expressed in normal B cells and in extramedullary plasma cells. It was found in most B-cell neoplasms, but expression in follicular lymphoma was weak (33/69) or negative (four cases). Similarly, CD19 expression in diffuse large B-cell lymphomas was weak (28/56) or negative (eight cases). In T-cell-rich B-cell lymphomas, CD19 was also weak (4/10) or negative (three cases). CD19 was often absent in post-transplant B lymphoproliferative disease, classical Hodgkin's disease and plasma cell neoplasms. An unexpected finding was the frequent absence of CD19 in the neoplastic cells in lymphocyte predominant Hodgkin's disease. Conclusions : CD19 can now be detected in routine biopsy specimens. In contrast to the classical pan-B marker CD20, CD19 is not always strongly expressed in B-cell neoplasms. Furthermore, the lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin's disease (which express most B-cell-associated markers) commonly lack CD19. [ABSTRACT FROM AUTHOR]

The use of flow cytometry to diagnose hematological malignancies has become routine due to its ability to often differentiate between morphologically similar diseases based on antigens expressed on the surface of malignant cells. In an attempt to expand on the utility of flow cytometry in the study of B-cell malignancies we have used the most reliable quantitative methodology, QIFI (quantitative indirect immunoflourescence assay), to study the expression of CD5, CD10, CD11c, CD19, CD20, CD22, CD23, and CD79b in 384 cases of several common B-lineage malignancies, including: B-ALL, CLL, SLL, hairy cell leukemia, diffuse large B-cell lymphoma, and follicular lymphoma. The impetus behind this extensive, single institution study of surface antigens was two-fold: evaluating similarities and differences of antigen expression between B-cell neoplasms and finding additional clinical utility for the quantitative flow cytometric data generated. Our results show that each distinct malignant histology has its own quantitative pattern of surface antigen expression. In most cases, these quantitative patterns do not increase the ability of flow cytometry to distinguish between them. However, a high expression of specific antigens on a given B-cell malignancy may potentially identify optimal therapeutic targets for current and/or future monoclonal antibody-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: B-cell clonal expansions (BCE) in young mice are transient, detectable for less than 4 weeks. In contrast, BCE in old mice persist more than 2 months. The greater persistence of BCE in old mice does not appear to be due to the age of the host as the survival of phenyloxazolone chicken serum albumin-induced BCE in most old mice was shorter than in young mice. This raises the possibility that persistent BCE seen in old mice develop over time from transient BCE present earlier in life. To test this hypothesis, young C57BL/6 mice were immunized with hen egg lysozyme (HEL) during the first year of life. By 28 months of age, the majority of these mice had developed a benign, persistent BCE associated with a HEL-specific serum mIg. We also investigated whether benign, persistent BCE, present in 18-month-old mice, can evolve into B-cell lymphomas. We observed that four of eight C57BL/6 mice that survived to 29 months of age had developed diffuse large cell lymphomas. In three of these mice, this diagnosis was made by microscopic analysis of the lymphoid organs. In one mouse, a macroscopic lymphoma was present that permitted us to demonstrate that the IgH mRNA CDR3 length and sequence in the malignant lymphoma was derived from a persistent BCE present 11 months earlier. Together these observations are consistent with the hypothesis that stepwise accumulation of genetic alterations combined with Darwinian selection underlies the evolution of B cells from transient BCE in young mice into persistent BCE, serum mIg, and B-cell lymphomas observed in older mice. [Copyright &y& Elsevier]

The aim of this study was to establish how effective is the use of immunohistochemistry on formalin-fixed bone marrow in diagnosing low-grade B-cell neoplasms. We investigated a series of 41 consecutive patients with bone marrow involvement for whom no other diagnostic tissues were available. The sections were stained with the following antibodies: CD3, CD20, CD79a, CD5, CD10, CD23, anti-cyclin D1 and kappa and lambda light chains. Antigen retrieval was performed using either a microwave oven or a pressure cooker. Labelling was performed with an avidin–biotin–peroxidase labelling system. A final diagnosis was reached in 37 out of 41 cases (90%): B-chronic lymphocytic leukaemia (15 cases), follicular lymphoma (10 cases), mantle-cell lymphoma (eight cases) and lymphoplasmacytoid lymphoma/immunocytoma (four cases). In the remaining four cases, a generic diagnosis of low-grade B-cell neoplasm was made. The immunophenotyping of formalin-fixed marrow is a useful technique for diagnosing most of the low-grade B-cell neoplasms. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 53-year-old woman who was admitted to the endocrinology clinic with a lump in the throat. Topics discussed diagnosis of acute lymphoblastic leukemia in the central nervous system; thyroid ultrasonography revealed moderate enlargement of bilateral thyroid lobes; and treatment of woman with drug methylprednisolone.

Lymphocytes leave the blood via post-capillary venules by binding initially to their specialized endothelium. CD44 is a 80-90 kDa hyaluronate-binding glycoprotein involved in binding to endothelium of high endothelial venules (HEV). LECAM-1 is a 75-85 kDa glycoprotein with lectin activity interacting with human peripheral lymph node vascular addressin (PNAd) on HEV. This immunohistochemical study shows that CD44 and LECAM-1 are essentially coordinately expressed on B-lymphocytes. The mode and level of CD44/ LECAM-1 expression dissect the peripheral B-cell development into stages that are closely linked to morphologically defined B-cell compartments. Although statistically correlated in B-cell leukaemias ( p<0.0009) and extranodal B-cell lymphomas ( p<0.003), expression of both molecules was less stringently coordinated in 127 B-cell neoplasms examined. B-cell chronic lymphocytic leukaemia, hairy cell leukaemia and mantle zone lymphoma were CD44/LECAM-1 positive, thus corresponding to their reactive counterparts. Correspondingly, follicular centre cell-derived lymphomas were devoid of both markers. Conversely, CD44 and LEC-AM-1 were infrequently detectable in extranodal malignant B-cell neoplasms, irrespective of their maturational state. Presence versus absence of CD44 and LECAM-1, alone or together, determined neither the leukaemic versus aleukaemic state nor the nodal versus extranodal tumour-forming phenotype of a B-cell tumour. [ABSTRACT FROM AUTHOR]

According to the World Health Organization (WHO) classification, the nosology of B-cell neoplasms integrates clinical, morphological, phenotypic, and genetic data. In this retrospective analysis, we identified 18 patients with isolated neoplastic lymphocytosis that could not be accurately classified within the WHO classification. Most of them were asymptomatic at the time of diagnosis and the evolution was relatively indolent, as only five patients required treatment after a median follow-up of 48 months. The neoplastic B-cells expressed CD5 in most cases, but the Royal Marsden Hospital score was strictly below 3. Trisomy 12 was the most frequent cytogenetic abnormality. High-throughput sequencing highlighted mutations found in both chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL). Similarly, the immunoglobulin heavy chain variable region repertoire was distinct from those reported in CLL or MZL. However, as treatment choice is dependent on the correct classification of the lymphoproliferative disorder, a histological diagnosis should be performed in case patients need to be treated. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 62-year-old male patient with abdominal pain in the left lumbar region. Computed tomography scanning was performed of the abdomen and thorax which showed the masses in the left and right adrenal gland. He underwent the chemotherapy that was completed in five months and patient has no sign of any radiological progression. The article discusses the presence of primary adrenal lymphoma (PML) in the cases of non-hodgkin lymphoma.

Primary non-Hodgkin's lymphoma's of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution., Competing Interests: The authors declare no competing interest.