scholarly journals Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: Discordance between Histology and Flow Cytometry in Bone Marrow Examination at Diagnosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1718-1718
Author(s):  
Fernando Martín Moro ◽  
Miguel Piris-Villaespesa ◽  
Monica Garcia Cosio ◽  
Jesus Villarrubia ◽  
Juan Marquet Palomanes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
Not Otherwise Specified ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Bone marrow (BM) examination is essential in the staging of diffuse large B-cell lymphoma (DLBCL). The assessment of BM involvement includes both histology (gold-standard) and flow cytometry (FC), but few studies have compared BM biopsy (BMB) histologic findings with results of FC analysis of BM aspirate. Discordance between both techniques generates debate about the staging and the prognostic significance in these cases. Methods: We performed a retrospective single-center analysis of patients with DLBCL, not otherwise specified (NOS) diagnosed during a 4-year period (2014-2017). Patients were divided in three groups according to BM findings of BMB and FC at diagnosis. Standard FC was performed by 4-color flow panel until 2016 and by 8-color FC since then. We described main characteristics of each group at diagnosis and analyzed survival outcomes. We applied means of descriptive statistics and Pearson's chi-squared test, and analyzed survival outcomes according to Kaplan-Meier, using Cox regression for comparisons. Results: We analyzed 59 cases, which were divided in three groups: 40 cases (67.8%) presented both negative histology and FC (BMB-/FC-), 10 (16.9%) showed BM involvement using both histology and FC (BMB+/FC+) and 9 cases (15.3%) presented discordant results, all of them with negative histology and positive FC (BMB-/FC+). Clinical and biological characteristics of each group at diagnosis are presented in Table 1. Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% (0.1-2.9) and 3/9 patients presented discordant immunophenotype of lymphoma cells between BM and node biopsy. If we considered BM infiltration as positive in all BMB-/FC+ cases, 4/9 (6.8% of all patients) would be upstaged. First-line treatment was homogeneous in all patients. With a median observation time of 18 months, progression-free survival (PFS) after 2 years was 67%, 22% and 22% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1A), with a multivariate hazard ratio (HR) of 1.9 (95% CI 1.2-2.9, p=0.004) and an univariate HR for FC+ (BMB-/FC+ and BMB+/FC+) vs FC- (BMB-/FC-) of 3.3 (95% CI 1.5-7.3, p=0.003). Two-year overall survival (OS) was 68%, 41% and 33% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1B); multivariate HR was 1.6 (95% CI 1.1-2.6, p=0.042) and univariate HR for FC+ vs FC- was 2.5 (95% CI 1.1-5.9, p=0.035). We found no significant difference between BMB-/FC+ and BMB+/FC+ in survival outcomes. Conclusions: In our series, the group with discordant BM infiltration (BMB-/FC+) presented worsen survival outcomes than BMB-/FC-. Such results should be validated in prospective studies because published series are retrospective and not focused specifically on DLBCL. BM infiltration detected by FC analysis but not by BMB could be considered as extranodal involvement at DLBCL NOS diagnosis. Disclosures García Gutiérrez: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau.

Intraocular Lymphoma: Diagnostic Approach and Immunophenotypic Findings in Vitrectomy Specimens

2009 ◽  
Vol 133 (8) ◽  
pp. 1233-1237 ◽  
Author(s):  
Kirtee Raparia ◽  
Chung-Che(Jeff) Chang ◽  
Patricia Chévez-Barrios
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Intraocular Lymphoma ◽  
B Cell Lymphomas ◽  
Not Otherwise Specified ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractContext.—Diagnosis and classification of primary intraocular lymphoma can be challenging because of the sparse cellularity of the vitreous specimens.Objective.—To classify and clinically correlate intraocular lymphoma according to the World Health Organization (WHO) classification by using vitrectomy specimens.Design.—Clinical history, cytologic preparations, flow cytometry reports, and outcome of 16 patients diagnosed with intraocular lymphoma were reviewed.Results.—The study group included 10 women and 6 men. The mean age of the patients was 63 years (range, 19–79 years). Eleven patients had central nervous system involvement and 6 patients had systemic involvement. All cases were adequately diagnosed and classified according to the WHO classification by using combination of cytologic preparations and 4-color flow cytometry with a limited panel of antibodies to CD19, CD20, CD5, CD10, and κ and λ light chains. The cases included 9 primary diffuse large B-cell lymphomas of the CNS type; 2 diffuse large B-cell lymphomas, not otherwise specified; 1 extranodal, low-grade, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT); 1 precursor B-lymphoblastic lymphoma; and 3 peripheral T-cell lymphomas, not otherwise specified. Of note, all 11 cases of diffuse large B-cell lymphoma were CD10−. All the patients received systemic chemotherapy and radiation therapy. Only 4 patients were free of disease at last follow-up (range, 18 months to 8 years), with severe visual loss.Conclusions.—Intraocular lymphoma cases can be adequately classified according to the WHO classification. Diffuse large B-cell lymphoma, CD10− and most likely of non–germinal center B-cell–like subgroup, is the most common subtype of non-Hodgkin lymphoma in this site, in contrast to ocular adnexal lymphoma for which MALT lymphoma is the most common subtype.

The prognostic significance of bone marrow involvement in diffuse large B cell lymphoma according to the flow cytometry

2019 ◽  
Vol 60 (10) ◽  
pp. 2477-2482 ◽  
Author(s):  
Uri Greenbaum ◽  
Itai Levi ◽  
Odelia Madmoni ◽  
Yotam Lior ◽  
Kayed Al-Athamen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Bone marrow infiltration by flow cytometry at diffuse large B‐cell lymphoma NOS diagnosis implies worse prognosis without considering bone marrow histology

2019 ◽  
Vol 98 (6) ◽  
pp. 525-528 ◽  
Author(s):  
Fernando Martín‐Moro ◽  
Miguel Piris‐Villaespesa ◽  
Juan Marquet‐Palomanes ◽  
Mónica García‐Cosío ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bone Marrow Infiltration ◽  
Bone Marrow Histology ◽  
Large B Cell Lymphoma ◽  
Worse Prognosis ◽  
Large B Cell

scholarly journals Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma NOS Diagnosis: Comparative Study between PET, Histology and Flow Cytometry

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Fernando Martin Moro ◽  
Miguel Piris-Villaespesa ◽  
Juan Marquet Palomanes ◽  
Claudia Lopez Prieto ◽  
Federico Santiago Herrera ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
False Negative ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Ann Arbor ◽  
Large B Cell

Introduction Bone marrow (BM) examination at diffuse large B-cell lymphoma (DLBCL) diagnosis is essential in staging and has prognostic implication. According to the last recommendations (Cheson, et al. JCO 2014) BM biopsy (BMB) is only needed for those patients with a negative BM infiltration by positron emission tomography (PET) for whom identification of occult discordant histology - whose biological and prognostic implications are unknown - is clinically important. Despite its greater sensitivity, flow cytometry (FC) is secondary in BM assessment. Our aim was to compare PET, BMB and FC in the study of BM infiltration at DLBCL diagnosis. Methods Retrospective study in two hospitals in Madrid of patients diagnosed with DLBCL NOS from January 2014 to January 2020. A complete BM assessment including PET, BMB and FC was performed in all included patients. The hole series (n=102) was analysed separately according with BM infiltration by each technique, differences between biological, clinical and laboratory variables were studied applying descriptive statistics tests when appropriate (Fisher's exact test, chi-square test, Student's T test and Mann-Witney U test). Event-free survival (EFS) and overall survival (OS) were analysed with Kaplan-Meier estimator according to BM infiltration positive vs negative for each technique, using Cox proportional-hazard model for comparisons. Results BM infiltration was not assessed in 2 patients by BMB and in 4 patients by FC due to technical reasons. Analysing separately the series according to BM infiltration by each technique (PET+ 25 vs PET- 77, BMB+ 15 vs BMB- 85 and FC+ 16 vs FC- 82) the basal characteristics were comparable between groups, except from extranodal sites ≥2, Ann Arbor III-IV and elevated LDH level in groups with positive BM infiltration. The variables associated with worsen EFS in univariate analysis were age ≥80 years (HR 2.31; CI 95% 1.1-5.1), cell-of-origin (COO) non-GCB (HR 2.33; CI 95% 1.1-4.9), extranodal sites ≥2 (HR 2.39; CI 95% 1.2-4.7), Ann Arbor III-IV (HR 4.55; CI 95% 2.0-10.5), and elevated LDH level (HR 2.32; CI 95% 1.1-4.7). The variables statistically related with worsen OS were COO non-GCB (HR 2.91; CI 95% 1.2-6.8), extranodal sites ≥2 (HR 2.61; CI 95% 1.2-5.5), Ann Arbor III-IV (HR 5.97; CI 95% 2.1-17.3), elevated LDH level (HR 2.36; CI 95% 1.1-5.4), and elevated beta-2 microglobulin level (HR 3.82; CI 95% 1.1-12.9). Double-expressor phenotype did not demonstrated association with EFS or OS. Median infiltration by FC analysis was 0.9% (0.05-27). The series distribution among BM infiltration is presented in Figure 1. Median follow-up was 25 months (0.3-90). Survival curves according to BM infiltration by PET, BMB and FC are presented in Figure 2. Univariate analysis among the type of infiltration by each technique are presented in Table 1. Multivariate analysis included age ≥80 years, COO non-GCB, BM FC+ and IPI score 3-5; BM infiltration by FC demonstrated no association with EFS (HR 2.2; CI 95% 0.9-5.3) or OS (HR 2.5; CI 95% 0.9-6.5). Conclusions BM infiltration by PET at DLBCL NOS diagnosis has not survival implication, contrary to infiltration demonstrated by BMB or FC. Cases with positive infiltration by PET but negative by BMB and FC could be false positive in PET or false negative in BMB/FC. According to our results the patients with discordant lymphoproliferative disorder BM infiltration presented worse prognosis and FC is probably the most important technique in this regard. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinicopathological Features and Prognosis of B-Cell Lymphoma, Unclassifiable, with Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma with t(14;18) and 8q24 Translocation in the Rituximab Era

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1633-1633
Author(s):  
Nozomi Niitsu ◽  
Naoki Takahashi ◽  
Mika Kohri ◽  
Norio Asou ◽  
Jun-ichi Tamaru ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Burkitt Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Pharmaceutical Research ◽  
B Cell Lymphoma ◽  
The Other ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases in terms of morphology, immunohistochemistry and molecular features. The t(14;18)(q32;q21) translocation juxtaposes the BCL2 gene, normally located at 18q21, with the IGH locus on 14q32. The t(14;18)(q32;q21) occurs in about 80-90% of follicular lymphomas and about 25-30% of de novo DLBCLs. On the other hand, the t(8;14)(q24;q32) translocation juxtaposes the c-MYC protooncogene, which is located at 8q24, to the immunoglobulin heavy chain (IGH) gene, located at 14q32, resulting in deregulated expression of c-MYC. t(8;14)(q24;q32) has been found in 80-90% of Burkitt lymphoma cases and in 5-15% of DLBCL cases. B-cell lymphoma having both t(14;18) and 8q24, so called double hit lymphoma (DHL), is rare. The pathological diagnosis in most cases of DHL is B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). Patients with DHL have elevated serum LDH levels, advanced stage, bone marrow involvement, extranodal involvement and the presence of B symptoms. In the present study, we evaluated the clinicopathological characteristics and prognoses of patients with BCLU with DHL. Patients and Methods: A total of 368 patients with DLBCL and BCLU were treated from 2007 to 2013. Chromosomal data were available in 195 of the 368 patients. Pathologic evaluation of the materials from each patient was performedat several central review meetings by six hematopathologists in the ALTSG pathology review board. Patients were treated with cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone (CyclOBEAP) regimen or CHOP regimen. Rituximab was administered to all patients. The median follow-up period was 44 months (range, 12-61 months). Results: t(14;18) + 8q24 dual translocation was seen in 18 (9.2 %) of the 195 patients with DLBCL and BCLU. There were 12 males and 6 females, with a median age of 62 (range, 47-76) years. Stage III/IV was found in 56%, bone marrow infiltration was found in 39％, central nervous system (CNS) infiltration was found in 17％, and high risk of international prognostic index (IPI) was found in 67％. Among the 18 patients with the DHL, extranodal sites of disease were bone marrow (7 patients), CNS (3 patients), pleural effusion (5 patients), and gastrointestinal tract (3 patients). Furthermore, 8 patients had at least two extranodal localizations. Immunophenotyping analysis (CD20, CD5, CD10, BCL2, BCL6, MUM1, Ki-67) was performed and showed BCLU with a germinal center type in all cases. Ki-67 staining ranged from 30-90%. All lymphoma cells were positive for CD20 and negative for CD5. CD10, BCL2, BCL6, and MUM1 were positive in 89%, 75%, 88%, and 19%, respectively. The 4-year overall survival (OS) rate was 72% among the patients with dual translocation (n=18) and 75% among the patients in the other chromosomal abnormalities group (n=177). The 4-year progression-free survival (PFS) rate was 52% among the patients with the dual translocation and 71% among the patients in the other chromosomal abnormalities group. The 4-year OS rate of the stage I/II and stage III/IV groups was 100% and 47%, respectively (P=0.016). We next examined the survival curve of patients in whom data on serum LDH levels were available. The 4-year OS rates of the high (>2N) and low LDH groups (<2N) were 33 and 100%, respectively (p=0.0002). According to the IPI, the 4-year OS of patients with L or L-I risk and those with H-I or H risk was 100% and 50%, respectively (p=0.03). Conclusions: Among patients with DHL, there was one subgroup that had a good prognosis. We elucidated the clinicopathological condition of especially the subgroup of DTL with poor prognosis, and prognostic improvement of this disorder is expected in the future by considering a new treatment strategy for these subgroups. Disclosures Niitsu: Chugai pharmaceutical: Research Funding. Takahashi:Chugai pharmaceutical: Research Funding. Kohri:Chugai pharmaceutical: Research Funding. Asou:Chugai pharmaceutical: Research Funding. Sakai:Chugai pharmaceutical: Research Funding. Miura:Chugai pharmaceutical: Research Funding. Okamoto:Chugai pharmaceutical: Research Funding.

Burkitt Lymphoma Has Lower CD58 Expression Than Other B Cell Malignancies in Children

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5011-5011
Author(s):  
Jonathan L. Metts ◽  
Silvia T. Bunting ◽  
Elizabeth P. Weinzierl ◽  
Traci Leong ◽  
Sunita I. Park
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Cell Adhesion ◽  
B Cell ◽  
Burkitt Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Malignancies ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Burkitt Lymphoma (BL) is a highly aggressive mature B cell neoplasm comprising 30% of Non-Hodgkin lymphoma in children. BL can be difficult to discriminate from other mature B cell lymphomas, and distinguishing BL from Diffuse Large B Cell Lymphoma (DLBCL) is a commonly encountered diagnostic dilemma. While c-myc translocation as detected by fluorescence in situ hybridization is more often associated with BL, DLBCLs may also have the translocation, and therapy is often started prior to obtaining this result. Early and rapidly obtained diagnostic clues would therefore be helpful to establish the appropriate therapeutic regimen. CD58 (aka LFA-3) is a cell adhesion molecule typically found on antigen presenting cells and is highly overexpressed in B-lymphoblastic leukemia (B-LL)(Chen et al, Blood 2001). In contrast, CD58 expression decreases as physiologic B cells mature in the bone marrow (Lee et al, Am J Clin Pathol 2005). Despite findings of abnormal CD58 expression in B-LL, CD58 expression by flow cytometry in BL and other mature B lymphomas, including DLBCL, has not been previously described in children or adults. Thus our objective was to investigate quantitative CD58 expression in BL and other pediatric B cell malignancies by flow cytometry. Methods: CD58 has been included in the flow cytometry diagnostic panel for all hematopoietic malignancies at our institution since 2009. In a single center retrospective study, we reviewed flow cytometry data from clinical specimens obtained at initial diagnosis of BL (n=18) and other mature B lymphomas (n=16) from 2009-2015. The "other mature B lymphomas" group consisted of DLBCL (n=6), post-transplant lymphoproliferative disorder (n=3), primary mediastinal large B cell lymphoma (n=2), pediatric follicular lymphoma (n=2), B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL (n=2), and extranodal marginal zone lymphoma (n=1). We also investigated CD58 expression of consecutive initial diagnostic bone marrow aspirates of B-LL (n=20) and Stage I-III hematogones (n=25) from bone marrow aspirates of patients with benign hematologic conditions (all from 2014). All samples included in this analysis were from patients 18 years of age or younger. CD58 expression was quantified as arbitrary mean fluorescence intensity (MFI) units. Initial comparisons were performed using a Kruskal-Wallis test, with post-hoc pairwise comparisons computed with the Nemenyi test. Results: CD58 expression by BL was found to be low (median MFI 427). In contrast, other mature B lymphomas and B-LL had significantly higher expression of CD58 when compared to BL (median MFI 1480 and 2342 respectively, p<0.0001 for both). Specifically, BL had lower CD58 expression than the DLBCL subgroup (n=6, median MFI 2142, p=0.0008). CD58 expression in BL was similar to that of Stage III hematogones/mature B lymphocytes (median MFI 569). Conclusions: Our data suggest that CD58 expression is significantly lower in BL compared to DLBCL, other mature B lymphomas, B-LL, and maturing B cells in pediatric patients. CD58 expression may be a useful diagnostic tool to discriminate BL from other pediatric B cell malignancies. Consistent with our data, low expression of cell adhesion molecules LFA-1 and CD58/LFA-3 in cultured Burkitt cell lines has been demonstrated previously (Billaud et al, Blood 1990), and our findings support the previous data. The authors also hypothesized that decreased expression of CD58 may serve as a mechanism of immune escape in BL. Correlation of CD58 surface proteins with RNA expression may be a first step to elucidate mechanistically why BL cells have decreased CD58, and how that may provide a survival advantage. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Can flow cytometry of bone marrow aspirate predict outcome of patients with diffuse large B cell lymphoma? A retrospective single centre study

2014 ◽  
Vol 33 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Ofir Wolach ◽  
Abigail Fraser ◽  
Michael Luchiansky ◽  
Chava Shapiro ◽  
Judith Radnay ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Single Centre ◽  
Large B Cell Lymphoma ◽  
Single Centre Study ◽  
Large B Cell
Sign in / Sign up

Export Citation Format

Share Document