Detection of Genetic Abnormalities for Diffuse Large B-Cell Lymphoma by Selective Interphase Analysis with FISH Method

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4149-4149
Author(s):  
Shi-Ping Jiang ◽  
Derek Bouman ◽  
Karine Hovanes
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
False Negative ◽  
B Cell Lymphoma ◽  
Fish Analysis ◽  
Neoplastic Cells ◽  
Interphase Fish ◽  
Large B Cell Lymphoma ◽  
Genetic Abnormalities ◽  
Large B Cell

Abstract Diffuse Large B-cell Lymphoma (DLBCL) accounts for approximately 30% of all lymphoid malignancies. It can be difficult to separate DLBCL from Burkitt lymphoma and plasmablastic myeloma by morphology and flow cytometric immunophenotyping alone. Fluorescent in situ hybridization (FISH) targetgene analysis can assist the differential diagnosis by detection of genetic abnormalities associated with DLBCL. Though no consistent numeric chromosomal abnormalities or translocations are observed as a hallmark for DLBCL, most cases have rearranged immunoglobulin heavy chain (IgH), BCL2 and MYC genes. Standard interphase FISH analysis is widely utilized to detect these genetic rearrangements. However, standard interphase FISH analysis could be falsely negative if the neoplastic cells are limited or if abundant benign cells are present in the background. Thus, the sensitivity to detect genetic abnormalities is low among the cases with a low number of neoplastic cells. Herein we present three DLBCL cases in which interphase FISH analysis was applied on selective cells that are morphologically consistent with neoplastic large lymphocytes. All three cases showed genetic changes in a high percentage of the selected cells. These three cases were originally analyzed for IgH gene rearrangement, IgH/BCL2 and IgH/MYC translocation by using standard non-selected interphase study and showed false negative results. However, by review of the H&E slide and the flow cytometry results prompted a re-evaluation of the FISH studies using selective analysis of neoplastic cells only. Our observations indicate that selective interphase FISH analysis improves the sensitivity of detecting genetic abnormalities in DLBCL. This analysis does require a corporation between hematopathologists and technologists performing interphase FISH studies.

scholarly journals Cytogenetic and Molecular Genetic Abnormalities of CIITA Gene in Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma

2021 ◽  
Vol 14 (2) ◽  
pp. 173-178
Author(s):  
Svetlana Aleksandrovna Kuznetsova ◽  
V.L. Surin ◽  
Ya.K. Mangasarova ◽  
T.Y. U Novikova ◽  
L.A. Grebenyuk ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Genetic ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Genetic Abnormalities ◽  
Large B Cell

Myeloperoxidase-Positive Intravascular Large B-Cell Lymphoma

2001 ◽  
Vol 125 (7) ◽  
pp. 948-950
Author(s):  
Phillip A. Conlin ◽  
Mageline B. Orden ◽  
Tiffany R. Hough ◽  
David L. Morgan
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Molecular Techniques ◽  
Neoplastic Cells ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
First Case ◽  
Large B Cell

Abstract Intravascular large B-cell lymphoma (IVLBL) is an uncommon form of non-Hodgkin lymphoma that is also known as malignant angioendotheliosis, intravascular lymphomatosis, and angiotropic large-cell lymphoma. The disease is characterized by a bizarre population of neoplastic cells, which are found systemically within vascular lumina. Although originally thought to be a neoplastic process of the endothelial cells, it has since been demonstrated, by molecular techniques and immunohistochemistry, that the neoplastic cells are of lymphoid origin. The differential diagnosis of these lesions includes granulocytic sarcomas that can be distinguished from IVLBL or other lymphomas by the presence of immunohistochemical positivity for myeloperoxidase. We describe a patient with a history of a myelodysplastic syndrome who subsequently developed IVLBL, which demonstrated immunohistochemical positivity for myeloperoxidase. To our knowledge, this represents the first case of a malignant lymphoma to demonstrate such findings.

scholarly journals An autopsy of intravascular large B-cell lymphoma with hemophagocytic syndrome

JRSM Open ◽  
2017 ◽  
Vol 8 (5) ◽  
pp. 205427041769505
Author(s):  
Hisanori Fukunaga ◽  
Kazumasa Kawashima ◽  
Hiromi Kumakawa ◽  
Yuko Hashimoto ◽  
Yuta Takahashi
Keyword(s):  
B Cell ◽  
Hemophagocytic Syndrome ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Neoplastic Cells ◽  
Small Vessels ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Intravascular large B-cell lymphoma presents with highly variable symptoms caused by the occlusion of small vessels by neoplastic cells in a variety of organs.

scholarly journals Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope

2021 ◽  
Vol 8 (7) ◽  
pp. 120
Author(s):  
Luca Aresu ◽  
Laura Marconato ◽  
Valeria Martini ◽  
Antonella Fanelli ◽  
Luca Licenziato ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Tumor Infiltrating Lymphocytes ◽  
B Cell Lymphoma ◽  
Immune Checkpoints ◽  
Ki67 Index ◽  
Neoplastic Cells ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain an insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with chemotherapy (n = 12) or chemoimmunotherapy with APAVAC (n = 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity.

State-of-the-Art Therapeutics: Diffuse Large B-Cell Lymphoma

2005 ◽  
Vol 23 (26) ◽  
pp. 6387-6393 ◽  
Author(s):  
Bertrand Coiffier
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Genetic Abnormalities ◽  
Risk Patients ◽  
Dose Dense ◽  
Definition Of ◽  
Large B Cell

This article is a review of the improvement in the treatment of patients with diffuse large B-cell lymphoma made during the last 10 years. Patients with diffuse large B-cell lymphoma now have a better outcome with longer survival because of two major developments: (1) increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense and/or dose-intense regimens; and (2) combining rituximab with chemotherapy. Both strategies were associated with higher response rates, lower relapse rates, longer event-free survival, longer time to progression, and longer overall survival, particularly in patients without adverse prognostic parameters. A combination of dose-dense, dose-intense regimens plus rituximab is currently being tested for poor-risk patients with diffuse large B-cell lymphoma. However, much work has to be done for patients with high-risk lymphoma. It may come with a better definition of genetic abnormalities specifically associated with refractoriness to chemotherapy.

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 Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-cell Lymphoma Detected by RNAscope

2021 ◽  
Author(s):  
Luca Aresu ◽  
Laura Marconato ◽  
Valeria Martini ◽  
Antonella Fanelli ◽  
Luca Licenziato ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Tumor Infiltrating Lymphocytes ◽  
B Cell Lymphoma ◽  
Immune Checkpoints ◽  
Ki67 Index ◽  
Neoplastic Cells ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with CHOP (n=12) or CHOP plus APAVAC (n= 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity.

The Secretion of Paraprotein Is Associated with Bone Marrow Involvement in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2646-2646
Author(s):  
Olga A. Gavrilina ◽  
Eugene E. Zvonkov ◽  
Elena N. Parovichnikova ◽  
Valeri G. Savchenko
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
M Protein ◽  
Fish Analysis ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Except multiple myeloma secretion of monoclonal paraprotein may be associated with several malignant conditions (lymphomas), they are produced by abnormally expanded single clone of plasma cells in an amount that can be detected in serum, urine, or rarely in other body fluids. A secretion of monoclonal paraprotein related to the neoplastic clone, was detected in more than 10% of newly diagnosed diffuse large B-cell lymphoma (DLBCL). M-protein in DLBCL might be easily missed, the rarity of associated clinical signs and the rapid fading during treatment. This group of DLBCL showed homogeneous morphologic and immunohistochemical features consistent with the non GCB-type. FISH analysis was negative for c-MYC gene rearrangements. M-protein in DLBCL patients, might be related to a very poor non GCB-type subset who should be given upfront intensified therapies [ASH 2012, abstract 2659]. The role and biological relevance of monoclonal paraprotein in diffuse large B-cell lymphoma is unknown. Aims: to compare the clinical and biological features of DLBCL patients with and without secretion of paraprotein. Patients and methods: We included in the study 86 high-risk DLBCL patients, diagnosed between July 2007 and September 2014. All patients were treated with intensified therapy (mNHL-BFM-90 or R-DA-EPOCH/R-HMA). 14 cases (16%) with monoclonal secretion paraprotein was identified. The Hans algorithm was used in order to classify cases of DLBCL as GCB-type and non GCB-type at the moment of diagnosis. Bone marrow involvement was identified by histological and B-cell clonality study. Results: We detected different types of protein in DLBCL: Mk (in 5 patients), Bence-Jones k (3 pts), Gk (2 pts), Ak (1 pts), Mλ (2 pts), Bence-Jones λ (2 pts), Gλ (2 pts), Aλ (1 pts). Four cases have shown 2 different clones simultaneously. Secretion ranged from trace to 27,1 g/l. 12 of 14 cases with monoclonal secretion were classified as non-GCB-type DLBCL. Characteristic of patients with monoclonal secretion were: stage III-IV; ECOG 2-3; median age 57 years (28-71); age ≥60y/<60y 43%/47%; M/F 71%/29%; IPI: 21% high-intermediate and 79% high risk; 93% with bone marrow involvement. We grouped the patients depending of bone marrow involvement, and according to the long-rank analysis only detection of monoclonal secretion of immunoglobulins was associated with bone marrow involvement in patients with diffuse large B-cell lymphoma (Table 1). Conclusions: Our study has shown that monoclonal secretion of paraprotein was associated with bone marrow involvement in patients with diffuse large B-cell lymphoma. Detection of secretion of paraprotein could help to suspect the cases with bone marrow involvement before the results of histology and when histology not informative. Diffuse large B-cell lymphoma with bone marrow involvement is characterized by aggressive course and poor response to standard chemotherapy. Disclosures No relevant conflicts of interest to declare.

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