A Highly Therapy-Resistant Case of B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma Showing Strong BCL2 Staining, Otherwise Indistinguishable from Burkitt Lymphoma (original) (raw)
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B-cell lymphoma, unclassifiable (B-UCL), with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, is a poorly characterized entity. Therefore, we investigated cases of B-UCL treated by the Nebraska Lymphoma Study Group (NLSG). We searched the NLSG registry for years 1985-2010 for cases of B-UCL. Immunohistochemical stains and fluorescence in situ hybridization studies for MYC, BCL2 and BCL6 gene rearrangements were performed. Among the 39 cases studied, 54% were male and 46% were female, with a median age of 69 years. The majority of patients presented with advanced-stage disease (62%) and had high (3-5) International Prognostic Index (IPI) scores (54%). The median overall survival (OS) was only 9 months and the 5-year OS was 30%. Patients with low IPI scores (0-2) had a better survival than those with high scores (3-5). The cases were genetically heterogeneous and included 11 'double-hit' lymphomas with rearrangements of both MYC and BCL2 or BCL6. None of the immunohistochemical or genetic features was predictive of survival. This B-cell lymphoma is a morphologically-recognizable entity with a spectrum of genetic abnormalities. New and better treatments are needed for this aggressive lymphoma.
Leukemia & Lymphoma, 2019
The 2016 World Health Organization (WHO) classification has designated two categories of high-grade B-cell lymphoma (HGBCL): HGBCL with MYC and BLC2 and/or BCL6 rearrangements (often referred to as "double/triple-hit" lymphoma), and HGBCL, not otherwise specified.[1] Optimal management of these aggressive malignancies remains uncertain. Historically, many HGBCL cases were classified as diffuse large B-cell lymphoma (DLBCL) and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), while others were designated as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BL)" (BCLU) and treated using high-intensity regimens (e.g. CODOX-M/IVAC or hyper-CVAD +/− rituximab).[2-4] Recently, the less intensive dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab regimen (DA-EPOCH-R) has been successfully applied in BL and in aggressive DLBCL (particularly double/triple-hit lymphomas) [5-9]. One concern with DA-EPOCH-R is that it omits systemic central nervous system (CNS) prophylaxis, while intraparenchymal brain recurrences are increasingly frequent in DLBCL and HGBCL [4, 10-13]. In contrast, high-intensity regimens include systemic high-dose methotrexate (HDMTX) which provides intraparenchymal CNS prophylaxis. Our objective was to describe progression-free survival (PFS) and risk of CNS recurrence among HGBCL and BL patients treated in our academic center, which cares for most patients with lymphoma diagnosed in Rhode Island. We integrated cancer registry and medical records for patients treated for BL or HGBCL between 2005 and 2017. HGBCL was defined as high-grade lymphoma with concurrent MYC and BCL2 and/or BCL6 rearrangements, or BCLU as diagnosed according to the 2008 WHO classification. All cases of BCLU were diagnosed according to the WHO criteria and reviewed by an academic hematopathologist (DOT) for inclusion in this study. Cases of
The American Journal of Surgical Pathology, 2010
B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "doublehit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathological spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we performed case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32-91). Six patients had a history of grade 1-2 follicular lymphoma (FL); review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 months) was inferior to both BL (p=0.002) and IPI-matched DLBCL (p=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (p<0.0001), Mum1/IRF4 (p=0.006), Ki-67 <95% (p<0.0001), and absence of EBV-EBER (p=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen in most BL controls (p=0.001), and exhibited a higher number of chromosomal aberrations (p=0.0009). DHL is a highgrade B-cell neoplasm with a poor prognosis, resistance to multi-agent chemotherapy, and clinical and pathological features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.
International Journal of Clinical and Experimental Pathology, 2012
B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new lymphoma entity which is recognized in the current World Health Organization (WHO) classification (2008). We report a case of a primary central nervous system lymphoma (PCNSL) with findings consistent with DLBCL/BL. It is characterized by a very aggressive clinical course, and a widespread multifocal involvement of the CNS. Our case shows that a DLBCL/BL can manifest in the CNS alone without any systemic involvement.
Indian Journal of Hematology and Blood Transfusion, 2015
B-cell lymphomas, unclassifiable; with features intermediate between large B-cell lymphoma and Burkitt lymphoma (BCLu-DLBCL/BL) is a new entity included in the recent World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues (2008) to overcome the problems of difficulty in classifying certain lymphomas having overlapping morphological, immunophenotypical and genetic features. To study the clinicopathological profile of BCLu-DLBCL/BL. Crosssectional study over 3 year period in the Haematology section of Department of Pathology in a large teaching hospital in Southern India from January 2011 to December 2013. All the cases reported as BCLu-DLBCL/BL were collected and the clinical, morphological and immunohistochemical parameters were analyzed. Descriptive statistics. There were seven cases, four males and three females, of age ranging from 20 to 70 years. Five cases had extranodal involvement. Four cases had Burkitt morphology with strong Bcl2 positivity and absent CD10 expression. One case had the morphology and immunophenotype that of typical BL, along with strong positivity to Bcl2 suggesting a double hit hypothesis. Two cases had morphology and immunophenotype of BL with low Ki 67. Three patients on follow up had adverse outcome. BCLu-DLBCL/BL, a provisional category in WHO 2008 is useful in classifying the cases not meeting the criteria for classical BL or DLBCL. Each of these cases was interesting with different sites of involvement, different morphological features and immunophenotype with most of the patients on follow up ending with a grave prognosis. Keywords BCLu-DLBCL/BL Á Burkitt lymphoma Á Diffuse large Bcell lymphoma Á Intermediate features Á WHO 2008 Key Message Though BCLu-DLBCL/BL requires morphological, immunophenotypical and genetic features for definitive diagnosis, nevertheless it helped us to categorize seven cases with Burkitt morphology with atypical immunophenotype, in spite of lack of facilities for genetic studies.
Adult Burkitt lymphoma- an Island between lymphomas and leukemias
Journal of Community Hospital Internal Medicine Perspectives
Background: Burkitt lymphoma is a rare, aggressive and rapidly fatal, B-cell non-Hodgkin 's lymphoma. It has an incidence of 0.4/100,000 age-adjusted to the USA standard population. Here we describe the case of a 77-year-old patient who presented with Burkitt lymphoma. Case: A 77-year-old male presented to his primary care physician with fatigue and listlessness and was referred to the hospital with a white blood cell count (WBC)-23.7 K/uL (neutrophils 37%, lymphocyte 11%, blasts 9%) and platelets-19 K/uL. During his stay in the hospital, repeat investigations revealed WBC-29.9 K/uL (neutrophils 22%, lymphocyte 27%, atypical lymphocytes 5%, blasts 20%) and platelets-10 K/uL with no evidence of mucosal bleeds, neck or abdominal masses or generalized lymphadenopathy. Bone marrow aspirate revealed the presence of MYC rearrangements (8q24) on flow cytometry and fluorescent in-situ hybridization (FISH), indicative but not typical of BL. He was transfused with platelets due to a rapidly deteriorating platelet count and episodes of epistaxis. He was discharged after four days with a plan of outpatient chemotherapy over a period of 4 months. An Ommaya reservoir was placed in the right ventricle for intrathecal chemotherapy. After four months of chemotherapy, computerized tomography of the chest, abdomen, and pelvis confirmed remission. A magnetic resonance imaging of the brain a month after completion of chemotherapy revealed metastatic lymphoma in the temporal, parietal and occipital lobes. He was discharged to hospice for palliative care. Conclusion: Unconventional presentations, as seen in our case of a leukemia-like picture in the absence of a bulky disease, are the quagmire that might delay aggressive management and result in poorer outcomes.
Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach
Hematological Oncology, 2009
Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an 'aggressive B-cell non-Hodgkin's lymphoma', characterized by a high degree of proliferation of the malignant cells and deregulation of the c-MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B-cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear-cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma', now listed in the updated WHO classification.
PubMed, 2011
Burkitt lymphoma (BL) is a well characterized entity. For atypical findings a term Burkitt-like lymphoma (B-LL) was applied in the past, but the interpretation of the morphological appearances was subjective and poorly reproducible. We used a combined approach (morphology using classical histological staining; immunohistochemistry-IHC; fluorescence in situ hybridization-FISH on interphase nuclei; cytogenetics) to perform a retrospective study on 39 patients diagnosed as BL and B-LL at our department in the years 1982 to 2002. By FISH we demonstrated t(8;14)(q24;q32) in 31 patients; in further two we found a break at 8q24, suggestive of a variant translocation. In three patients with the cytogenetic investigation available we confirmed the findings of FISH--two lymphomas had the t(8;14)(q24;q32), one had t(2;8)(p12;q24). IHC showed CD20, CD10, BCL-6, p53 expression, and Ki-67 antigen in > 95% of the tumor cell population in a majority of the patients. There was a group of 4 patients in whom the t(8;14)(q24;q32) or a break at 8q24 were not found (FISH). These cases were reclassified within the WHO defined grey zone subgroup of B-cell lymphoma unclassifiable with features intermediate between diffuse large cell lymphoma (DLBCL) and Burkitt lymphoma--I-DLBCL/BL. Two further cases were reclassified as DLBCL based on a combined IHC and FISH findings. A lymphoma of one of these patients had breaks at 3q27 (BCL6) and at 14q32 (IGH) suggestive of t(3;14)(q27;q32). The overall survival estimate of 33 patients with the diagnosis of BL was 54%. Most of deaths occurred within 6 months after the tumor diagnosis. The unfavorable clinical outcome appears to be associated with a strong expression of the p53 protein in the tumor cell population. Individually utilized methods in the diagnosis of BL may lead to false diagnostic conclusions. A combined approach helps to establish a more reliable diagnosis of BL and to separate grey zone lymphomas I-DLBCL/BL and DLBCL with morphological mimics of BL to start adequate treatment. I-DLBCL/BL is a non-homogenous group of lymphomas necessitating further analysis in a prospective study.
Leukemia, 2005
* IgH = immunoglobulin heavy chain gene; Ig-kappa = immunoglobulin kappa light chain gene; Ig-lambda = immunoglobulin lambda light chain gene. Treatment of relapse Young patients with aggressive lymphoma relapsing after first-line treatment may still be cured by myeloablative chemo-and or radiotherapy followed by autologous stem cell transplantation, provided they still have chemosensitive disease, i.e. respond to second-line chemotherapy. 39 Current practice is largely based on the evidence from the PARMA study, a randomized multicenter trial in 215 patients with aggressive lymphoma who relapsed after first-line doxorubicin containing chemotherapy. After two courses of conventional second-line chemotherapy, responding patients were randomly assigned to receive either four additional courses of chemotherapy plus radiotherapy, or radiotherapy plus intensive chemotherapy followed by autologous bone marrow transplantation. Patients with resistant disease, i.e. those with less than partial response after the 2 nd chemotherapy course, went off protocol treatment. At five years the survival of patients in the transplantation arm was significantly superior to those in the chemotherapy arm: 53% versus 32%. However, only half of the patients responded to second-line chemotherapy. Patients who had relapsed early, i.e. during first-line chemotherapy, had a much lower response rate to second-line chemotherapy than patients with late relapse 21% versus 64%. 39 Patients not responding to second-line treatment had dismal survival. Time to relapse after first-line chemotherapy, and serum-LDH at relapse were independent prognostic factors for response to second-line therapy. 54 Because only patients responding to second-line chemotherapy will be candidates for ASCT, we wondered whether the IPI at relapse, i.e. the secondary age-adjusted IPI would also have prognostic relevance in patients who actually receive ASCT, i.e. those with chemosensitive relapsed aggressive lymphoma. The results of a retrospective study investigating prognostic factors in chemosensitive patients transplanted for relapsed or primary progressive aggressive lymphoma in our hospital (UMCG) are presented in chapter 5.1 of this thesis. In the meantime, the independent prognostic significance of this secondary IPI in patients with relapsed or primary progressive diffuse large B-cell lymphoma has also been confirmed by others. 9 Chemosensitivity remains the most important factor for the prediction of outcome in patients failing first line chemotherapy and the early detection of these patients has important clinical consequences. Given the uncertainties of CT scanning in the prediction of response, FDG-PET might be a better predictor for true chemosensitive disease in these patients. A pilot study investigating this issue in patients with relapsed lymphoma is presented in chapter 5.2.