Case Of Burkitt's Lymphoma Research Articles

Primary Burkitt lymphoma of breast presented by bilateral breast enlargement

Burkitt lymphoma is a very aggressive B cell lymphoma, which can rarely involve breast tissue. Although it usually affects children, but primary breast lymphomas usually, occur in older age. In this report, we present a rare case of Burkitt lymphoma in a 40-year-old woman primarily presented by bilateral breast enlargement which shortly followed by gastrointestinal and bone marrow involvement.

Benefits of Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma.

Objective: The aim was to study the benefits and risks of anti-CD19 chimeric antigen receptor (CAR) T-cells in adults with B-cell lymphoma. Methods: From October 2015 to October 2021, we treated five patients with B-cell lymphoma, comprising two with mantle cell lymphoma, one case of Burkitt lymphoma, one case of diffuse large B-cell lymphoma, and one case of chronic lymphocytic leukemia/small lymphocytic lymphoma. The patients were given the FC regimen 5 days before the infusion of anti-CD19 CAR T-cells. The median total number of CAR T-cells infusions was 350*10^6 (88*10^6–585*10^6). Results: 1) Patients who received CAR T-cell induction therapy achieved complete remission (CR) in Case 1 and Case 3 and partial remission (PR) in Case 2. Case 3’s ATM and D13S25 gene deletions were negative 42 days after CAR T-cell therapy, and molecular biology CR (mCR) and minimal residual disease (MRD) were negative for 5 years and 6 months. The patient in Case 3 was cured. 2) Case 4 patient’s TP53 gene mutation became negative 1 month after CAR T-cell therapy. MRD was negative after CAR T-cell therapy at 41 and 42 months in Cases 4 and 5, respectively. 3) Case 1∼Case 3 patients developed cytokine release syndrome (CRS) without encephalopathy syndrome, accompanied with serious adverse events. CRS can be effectively managed with tocilizumab, etanercept, glucocorticoids, and plasmapheresis. Conclusion: Anti-CD19 CAR T-cell therapy is effective in treating relapsed/refractory B-cell lymphoma, and the side effects of CAR T-cell therapy can be properly managed. CAR T-cell therapy has high efficacy and presented no side effects in the treatment of MRD in B-cell lymphoma (NCT03685786, NCT02456350).

Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines

Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Methods: In this study, we mapped the chromosomal integration sites of EBV (EBV-IS) into the genome of 21 EBV+ BL cell lines (BL-CL) using metaphase fluorescence in situ hybridization (FISH). The data were used to investigate the EBV-IS distribution pattern in BL-CL, its relation to the genome instability, and to assess its association to common fragile sites and episomes. Results: We detected a total of 459 EBV-IS integrated into multiple genome localizations with a preference for gene-poor chromosomes. We did not observe any preferential affinity of EBV to integrate into common and rare fragile sites or enrichment of EBV-IS at the chromosomal breakpoints of the BL-CL analyzed here, as other DNA viruses do. Conclusions: We identified a non-random integration pattern into 13 cytobands, of which eight overlap with the EBV-IS in EBV-transformed lymphoblastoid cell lines and with a preference for gene- and CpGs-poor G-positive cytobands. Moreover, it has been demonstrated that the episomal form of EBV interacts in a non-random manner with gene-poor and AT-rich regions in EBV+ cell lines, which may explain the observed affinity for G-positive cytobands in the EBV integration process. Our results provide new insights into the patterns of EBV integration in BL-CL at the chromosomal level, revealing an unexpected connection between the episomal and integrated forms of EBV.

急性虫垂炎を合併した虫垂原発Burkitt lymphomaの1例

急性虫垂炎を合併した虫垂原発Burkitt lymphomaの1例

Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.

S3199 A Rare Case of Primary Gastric Burkitt Lymphoma

S3199 A Rare Case of Primary Gastric Burkitt Lymphoma

FBXO11 Is Recurrently Mutated in Burkitt Lymphoma and Its Inactivation Accelerates Lymphomagenesis in Eμ-Myc mice

INTRODUCTIONBCL6 is a key oncogene in lymphoma pathogenesis. Malignant lymphoid cells exploit several mechanisms to deregulate the expression of BCL6, including chromosomal translocations, somatic mutations in the promoter regulatory regions or inactivation of the pathway that controls its degradation. FBXO11 was recently identified as a major ubiquitin ligase involved in the degradation of BCL6 and was found to be frequently inactivated by mutations or deletion in diffuse large B cell lymphoma (DLBCL). Thus, FBXO11 acts as an oncosuppressor in DLBCL by promoting the accumulation of BCL6. Given the prominent role of FBXO11 in regulating BCL6 stability, we searched for FBXO11 mutations in BCL6-positive lymphomas, other than DLBCL, and we investigated its role in lymphoma development in vivo .METHODSWe sequenced the entire FBXO11 coding sequence by classical Sanger sequencing in 100 cases of Follicular Lymphoma (FL), 36 cases of Burkitt Lymphoma (BL), 8 BL cell lines and 8 Anaplastic Large cell lymphoma cell lines, all BCL6-positive lymphomas. Moreover, we sequenced 50 cases of Marginal Zone B cell Lymphoma (MZL), which show variable expression of BCL6.We functionally validated the FBXO11 mutations by developing mutant constructs and testing their ability to induce BCL6 and SNAIL degradation. We then applied the CRISPR/Cas9 system to disrupt the endogenous FBXO11 gene in BL cells and evaluated its effect on BCL6 stability.To dissect the in vivo role of FBXO11 in lymphomagenesis we generated conditional FBXO11 knock-out (KO) mice (FBXO11fl/fl) to delete protein expression in CD19-positive B cells. To investigate whether FBXO11 inactivation cooperates with c-myc in lymphomagenesis we crossed CD19/Cre-FBXO11fl/fl mice with Eμ-myc transgenic mice .RESULTSWe identified FBXO11 mutations in BL cases and cell lines (10/44, 22.7%), one case of FL (1/100) and one case of MZL (1/50). In FL and MZL, the mutational analysis of tissue collected by microdissection showed that the mutation was specifically acquired by the high-grade component. The frequency of FBXO11 mutation in BL was further validated on an independent cohort of 51 BL cases (6/51, 11.7%), obtained from published data of a previous whole-exome sequencing study (Love et al, Nat Genet. 2012).BL mutations were mostly missense mutations located in the functional CASH domains and also splice-site mutations that were never described before and that induced alternative splicing, as confirmed on the mRNA extracted from the tumor samples. All mutations produced a mutant FBXO11 with impaired ability to induce BCL6 and SNAIL degradation. CRISPR/Cas9 mediated KO of FBXO11 in BL cells resulted in an almost complete stabilization of BCL6, thus suggesting that FBXO11 is the main, if not unique, ubiquitin ligase that controls BCL6 stability in BL.Finally we observed an acceleration of lymphoma development in the CD19/Cre-FBXO11fl/fl mice crossed with Eμ-myc transgenic mice. The lymphomas showed histologic features of high-grade disease with a more mature B-cell phenotype, than the Eμ-myc tumors alone.CONCLUSIONSOverall our results demonstrate that FBXO11 is frequently mutated in BL. All mutants identified impair the ability of FBXO11 to regulate the degradation of BCL6. Together with our previous findings (Duan et al, Nature 2012), this study shows that FBXO11 is mostly mutated in aggressive lymphomas such as DLBCL and BL, and suggests that FBXO11 mutations could contribute to their aggressiveness. In fact, we show that FBXO11 inactivation cooperates with c-myc in accelerating lymphomagenesis. We have established a novel murine lymphoma model that resembles more closely the human BL, providing a novel promising tool for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches with BCL6 and/or c-myc inhibitors. DisclosuresNo relevant conflicts of interest to declare.

B- Cell Maturation Antigen Is Exclusively Expressed in a Wide Range of B-Cell and Plasma Cell Neoplasm and in a Potential Therapeutic Target for Bcma Directed Therapies

Background: BCMA (TNFRSF17 or CD269) is a cell surface protein expressed on a subset of B cells and mature plasma cells. It is related to BAFF receptor, transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI). When engaged by their ligands APRIL and BAFF these three receptors induce B cell maturation and differentiation into plasma cells. BCMA (B cell Maturation Antigen) is also expressed in B cell lymphoma and plasma cell neoplasms including myeloma. Because of this restricted expression, it has emerged as a potential therapeutic target. A number of clinical trials using either chimeric antigen receptor T cells or antibody drug conjugates targeting BCMA have been initiated to treat plasma cell myeloma and B cell lymphomas. Although the expression of BCMA has been investigated in experimental models and cell lines, no clinical grade assays that can assess BCMA expression in routine clinical specimens, in particular, in decalcified formalin fixed paraffin embedded (FFPE) bone marrow biopsies, with high specificity and sensitivity have been established. Screening patients who may be appropraite candidates for BCMA targeted therapy is therfore challenging. Given the new therapies targeting BCMA, we developed and validated a clinical grade assay to assess BCMA expression on B and plasma cell malignancies on routine FFPE specimen in clinical practice.Material and Methods: Total of 672 routine tissue and decalcified bone marrow biopsies were prospectively stained with anti-BCMA immunostain (Santa Cruz; Clone D6 Mouse Monoclonal Antibody) using standard methods. The cases included normal lymphoid tissues (n=45), B cell lymphoma (n=278), plasma cell neoplasms (multiple myeloma, n=162; plasmacytoma, n=13), other hematopoietic neoplasm and carcinomas (n=31 and 42, respectively). B cell lymphomas included low grade CLL/SLL, mantle cell lymphoma, marginal zone lymphoma and lymphoplasmacytic lymphoma and high grade lymphomas diffuse large B cell lymphoma (DLBCL), Burkitt and plasmablastic lymphoma. Sections from tonsils and reactive lymph nodes were used as a control. We developed a scoring system based on the predominant pattern (Golgi, membranous, Golgi and membranous), intensity (1+, 2+, 3+) and percentage (0-100%). We used >20% BCMA expression in the neoplastic cells as the positive cut off.Results: In normal lymphoid tissues, BCMA expression was restricted to plasma cells and germinal center B cells. BCMA expression was not detected in other tissues (epithelium, T cells, dendritic cells and histiocytes/macrophages). BCMA showed a high level of expression in B cell lineage malignancies and plasma cell neoplasms. 97.1% cases of plasma cell neoplasms were positive for BCMA with predominant Golgi and membranous pattern and strong (3+) intensity. B cell neoplasms (DLBCL and low grade B lymphomas) predominately showed membranous pattern with 2-3+ staining intensity. High grade lymphomas (Burkitt and plamablastic lymphoma) showed strong (3+) intensity with both membranous and Golgi pattern. In DLBCL, both ABC and GCB subtypes expressed BCMA but there was no significant difference in the intensity and pattern of staining (ABC type=39.1% vs. GCB type=35.1%). Among follicular lymphomas no significant difference was observed between grade 1-2 and grade 3. Eight cases (87.5%) of Burkitt lymphoma and seven cases (100%) of plasmablastic lymphoma showed strong and diffuse BCMA expression (3+ intensity; membranous and Golgi pattern). T cell lymphoma, Hodgkin lymphoma and myeloid and lymphoblastic lymphoma/leukemia were negative for BCMA immunostain. The results are summarized in Table 1 and Figure 1.Conclusion: This study shows broad expression of BCMA in a wide range of B and plasma cell neoplasms using a clinical grade assay, but not in normal tissues outside the lymphoid system or in other epithelial and hematopoietic neoplasms. BCMA expression is seen in many more B cell malignancies than previously recognized, including in a number of aggressive B cell neoplasms such as high grade B-cell lymphomas Burkitt and plasmablastic lymphomas. These findings suggest that the diseases that could be targeted by novel BCMA directed therapies are broader than previously realized. This assay will allow biomarker based selection of patients for BCMA targeted trials, and the semi-quantitative nature of the assay may allow the prediction of clinical outcomes for such therapies [Display omitted] DisclosuresSmith:Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: BCMA targeted CAR T cells, Research Funding. Dogan:Peer Review Institute: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche Pharmaceuticals: Consultancy; Celgene: Consultancy.

A rare case of pediatric pancreatic Burkitt lymphoma

A rare case of pediatric pancreatic Burkitt lymphoma

A Rare Case of Burkitt Lymphoma in a 13-year-girl

A Rare Case of Burkitt Lymphoma in a 13-year-girl

A Case of Primary Burkitt Lymphoma of the Bladder

The most frequent primary lymphomas of the bladder are the low-grade B-cell- derived non-Hodgkin’s lymphomas of the MALT type, including Burkitt’s lymphoma. Primary genitourinary localization of lymphomas is uncommon and, in particular supra vesical development of Burkitt lymphoma. The continuous progress of treatment by chemotherapy has changed the pejorative prognosis of this disease into a good one.

The "Burkitt-like" immunophenotype and genotype is rarely encountered in diffuse large B cell lymphoma and high-grade B cell lymphoma, NOS.

Burkitt lymphoma (BL) is a B cell lymphoma composed of monomorphic medium-sized blastic cells with basophilic cytoplasm and a high proliferation index. BL has a characteristic immunophenotype of CD10 and BCL6 positive and BCL2 negative and harbours MYC gene rearrangements (MYCR) in >90% of the cases. Owing to its highly aggressive nature, intensified chemotherapy regimens are usually administered, requiring an exact diagnosis. Since the diagnosis usually warrants an integration of morphologic, immunophenotypic and genetic findings and because there is a morphologic overlap with the new WHO category of high-grade B cell lymphoma, not otherwise specified (HGBL, NOS) and some cases of diffuse large B cell lymphoma (DLBCL), we wanted to test the distinctiveness of the CD10+, BCL6+, BCL2- and MYCR positive immunopheno-genotype in a large cohort of >1000 DLBCL and HGBL. Only 9/982 DLBCL classified by an expert panel of haematopathologists (0.9%) displayed a single MYCR and were CD10+, BCL6+ and BCL2-. In a similar fashion, only one out of 32 HGBL, NOS (3%) displayed the "Burkitt-like" genetic/immunophenotypic constitution. The samples of non-BL showing the BL-typic immunopheno-genotype, interestingly, harboured higher copy number variations (CNV) by OncoScan analysis (mean 7.3 CNVs/sample; range: 2-13 vs. 2.4; range 0-6) and were also distinct from pleomorphic BL cases regarding their mutational spectrum by NGS analysis. This implies that the characteristic immunophenotype of BL, in concert with a single MYCR, is uncommon in these aggressive lymphomas, and that this constellation favours BL.

Clinical profile, outcome and challenges in the management of pediatric Burkitt lymphoma: a single center experience

This study was conducted with the aim to assess the clinico-pathological profile, treatment outcomes and the challenges faced in Low Middle Income Countries (LMIC) during management of pediatric Burkitt lymphoma cases on intensive chemotherapy protocol. This was a single center retrospective analysis of pediatric Burkitt lymphoma cases (age <18 years) managed uniformly with Lymphomes Malins B (LMB) 96 chemotherapy protocol between January 2015 and September 2019. 40 cases were analyzed with a median age 11.5 years (range 4–18 years) and male: female ratio =4.7:1. Patients belonging to different LMB risk groups were: A-3 (7.5%), B-31 (77.5%), and C-06 (15%). 25 (62.5%) patients had abdominal disease at presentation. The survival analysis of different treatment risk groups showed statistically significant difference in mean Overall Survival (OS) between group A-100%, group B- 87%±6.1% and group C-44.4%±16.2%; (p value = .016). On multivariate analysis of prognostic factors affecting survival, CNS involvement (p value = .03) and median time from diagnosis to treatment initiation more than 30 days (p value = .04) were significantly associated with poor outcome. Incidence of culture positive febrile neutropenia episodes was 28.2% of which 69.2% infections were caused due to carbapenem resistant gram-negative organisms. In our study, although the outcomes in risk group A and B patients were comparable to LMB 96 treatment results, the outcome in risk group C was considerably poor primarily due to advanced disease at presentation and delayed diagnosis. The critical challenges that we faced in our cohort were delayed diagnosis, treatment cost affordability, poor nutritional status, and high infection related mortality.

Two cases of Burkitt lymphoma in the paranasal sinuses in children with rapid onset of visual impairment

Two cases of Burkitt lymphoma in the paranasal sinuses in children with rapid onset of visual impairment

Pathological fracture of the knee revealing Burkitt lymphoma: a case report

Burkitt lymphoma (BL) is a highly mature B-cell non-Hodgkin lymphoma that presents 1 to 2% of all adult lymphomas. Its pathophysiology is still poorly defined. The prognosis depends on the location and stage. Clinical manifestations are not specific however the most common symptoms are pain and mass. Burkitt lymphoma can be subcategorized into 3 variants: endemic; sporadic; and BL with immunodeficiency, typically infection with HIV. Bone involvement in this type of lymphoma is a rare event; very few reports about this entity exist in the literature. We report the case of bone Burkitt lymphoma in a 49-year-old female patient who presented 1 month before his admission with the pain of the left knee and abdominal pain, progressing in a context of alteration of general condition. The clinical examination found a performance status of 1, local examination revealed partial functional impotence of the knee with severe pain on palpation and on active and passive mobilization. Standard X-ray of the knee revealed a fracture of the upper and tibia, CT scan of the knee revealed a process of osteolytic epiphyseal-metaphyseal with tissue damage of the tibia and invasion of soft tissue with multiple nodular intramedullary epiphyseal. The biopsy of the mass with anatomopathological and immunohistochemical examination showed a tumor proliferation of lymphoid cells with CD20+, BCL 6+, and CD10 +, MUM1+, with a 100% KI 67, the diagnosis of Burkitt lymphoma (BL) was confirmed. The C-TAP CT scan shows an abdominal mass, the BOM was normal, the myelogram was normal, Lactate dehydrogenase (LDH) was elevated to 590 IU/L. The patient was put on the R-CODOX-M/R-IVAC protocol. Burkitt lymphoma is a rapidly proliferating tumor with a poor prognosis, it's suspected in any abdominal masses. Bone involvement as a revealing event in this type of lymphoma is a very rare event and the diagnosis should be established quickly followed by rapid initiation of definitive treatment for a better prognosis.

Primary Osseous Burkitt Lymphoma Mimicking Multiple Myeloma – A Case Report and Review of Literature

Burkitt lymphoma (BL) is one of the aggressive subtypes of non-Hodgkin lymphoma commonly seen among pediatric and young population. Primary BL of pelvic bone presenting with back pain, paraparesis, and multifocal osteolytic lesion in the elderly is a rare entity. We report a case of primary BL of pelvic bone in a 65-year-old female presenting with back pain and paraparesis, facing diagnostic dilemma as the lesions were radiologically mimicking multiple myeloma. Subsequently, bone marrow flowcytometry and cytogenetic evaluation by fluorescence insitu hybridization confirmed the diagnosis. We highlight the diagnostic challenge, clinical presentation, and treatment strategy in such a rare case along with a review of literature.

An Atypical Case of Burkitt Lymphoma with Diffuse Peritoneal, Omental and Periportal Invasion

Diffuse peritoneal and especially periportal invasion of Burkitt lymphoma is very rarely seen. We present a case of a 16-year-old boy presenting with abdominal pain and constipation, without improvement after enemas. Abdominal ultrasound revealed a diffuse infiltrating peritoneal mass, omental caking, ascites, and a periportal mass, confirmed by computed tomography (CT). No lymphadenopathies were seen. Biopsy was performed and the diagnosis of Burkitt lymphoma was made. Although very rare, it is important to include lymphoma in the differential diagnosis of diffuse peritoneal and periportal invasion in children, as it can mimic peritoneal carcinomatosis.

Successful Treatment of Pediatric Refractory Burkitt Lymphoma PTLD after Liver Transplantation using Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

In the immunocompromised setting, recipients of solid-organ or hematopoietic stem-cell transplants carry an increased risk of post-transplant lymphoproliferative disorder (PTLD). Burkitt lymphoma (BL) PTLD is a rare form of monomorphic B-cell PTLD, which lacks a standard best treatment. Here, we report the successful treatment of refractory BL-PTLD with autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. A male patient was diagnosed with BL-PTLD, with an increasing Epstein-Barr virus (EBV) viral load, at 21 months after undergoing living liver transplantation from his mother due to neonatal biliary atresia. After 10 cycles rituximab +/− intensive chemotherapy and surgical tumor resection, the tumors significantly advanced. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tumor tissue, revealing one mutation in exon 5, TP53: p.A159 V, which may be associated with chemo-resistance. Thus, treatment was started with autologous anti-CD19 CAR T-cell therapy. We administered 9.0 × 106/kg autologous anti-CD19 CAR T-cells, after conditioning with cyclophosphamide and fludarabine. Unexpectedly, the patient experienced only mild (Grade II) cytokine release syndrome (CRS) without neurotoxicity. Finally, he went into complete remission (CR), and has achieved 16-month event-free survival to date. In addition, liver function has remained stably within the normal range without any immunosuppressive therapy. The literature includes only five previously reported BL cases treated with CAR T-cell therapy. In conclusion, the present case suggests that autologous anti-CD19 CAR T-cell therapy may represent a new therapeutic option for some cases of refractory BL-PTLD. Clinical trial number: ChiCTR2000032211.

Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas

The Epstein–Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a “hit-and-run” mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm

Objective/backgroundB-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenström’s macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88 L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms. MethodsA total of 110 consecutive cases of B-cell neoplasms showing peripheral blood and/or bone marrow infiltration were included. MYD88 L265P mutation was detected by polymerase chain reaction amplification of exon 5 of MYD88 gene, followed by restriction fragment length polymorphism analysis. ResultsAmong the 110 cases, the major group was of CLL (54.5%, n = 60), followed by HCL. Other cases included MCL, LPL, DLBCL, SMZL, NMZL, FL, and BL. MYD88 L265P mutation was seen in 21 (19.1%) cases of B-cell neoplasm, whereas 89 (80.9%) cases were negative for MYD88 L265P mutation. It was most commonly seen in LPL/WM cases followed by HCL, SMZL, CLL, and MCL cases. No case of DLBCL, FL, and BL showed MYD88 L265P mutation. Statistically significant difference was seen for hemoglobin level in CLL cases, with MYD88 L265P mutated cases showing higher mean hemoglobin levels than MYD88 wild-type cases (p = .001). For other parameters, no statistically significant difference was noted between mutated and unmutated cases. ConclusionMYD88 L265P mutation is seen in various B-cell neoplasms; it is most commonly seen in LPL/WM cases but not specific for it.