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Query: UMLS:C0855152 (Primary mediastinal large B-cell lymphoma)
 46 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary mediastinal large B-cell lymphoma (PMBL), currently recognized as a diffuse large B-cell lymphoma (DLBCL) subtype, shows increased expression of interleukin 4 (IL-4)/IL-13 signaling effectors and targets, suggesting constitutive activation of these pathways. We therefore investigated the functional state of the signal transducer and activator of transcription 6 (STAT6), mediating IL-4/IL-13 transcriptional effects. Constitutive STAT6 phosphorylation and DNA-binding activity were detected in PMBL cell lines but not DLBCL cell lines. Moreover, immunohistochemical analysis revealed nuclear phosphorylated STAT6 (P-STAT6) in 8 of 11 PMBL, compared with 1 of 10 DLBCL primary tumors (P =.01). IL-4 and IL-13 transcripts were absent in PMBL cell lines and expressed at low levels in tumors, indicating that, contrary to classical Hodgkin lymphoma (cHL), STAT6 activation is not due to an autocrine IL-4/IL-13 secretion. We demonstrated an amplification of the JAK2 gene in 2 of 6 PMBL cases, and showed higher JAK2 mRNA levels in PMBL compared with DLBCL (P =.005). The Janus kinase 2 (JAK2) was constitutively phosphorylated in the PMBL MedB1 cell line. MedB1 treatment with JAK2 inhibitor AG490 partially decreased STAT6 phosphorylation, suggesting that JAK2 is partially involved in STAT6 activation in these cells. Our findings highlight phosphorylated STAT6 as a characteristic distinguishing PMBL from DLBCL, but a common feature to PMBL and cHL, supporting the hypothesis of common pathogenic events in these 2 lymphomas.
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PMID:Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma. 1504 51

Primary mediastinal large B-cell lymphoma is a well-defined lymphoma entity whose molecular pathogenesis is incompletely understood and also lacking well-established diagnostic markers. Recently, the presence of overlapping features between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma was highlighted by gene expression profiling as well as morphological studies. We investigated the expression of TP73L (commonly known as p63) isoforms in primary mediastinal large B-cell lymphoma at both protein and mRNA level, and demonstrated the exclusive presence of transactivating (TA) isoforms in all cases. We also demonstrated that TP73L is expressed in a subset of germinal center B-cells, as well as in some diffuse large B-cell lymphomas, but it is never present in classical Hodgkin lymphoma. Nodular lymphocyte predominant Hodgkin's lymphoma also showed TP73L positivity by immunohistochemistry. Isoform analysis by real-time PCR showed that TA-TP73Lalpha is the most represented in primary mediastinal large B-cell lymphoma, but TA-TP73Lgamma is the most differentially expressed in comparison to both germinal center B-cells and diffuse large B-cell lymphomas. TP73L expression proved a useful diagnostic marker of primary mediastinal large B-cell lymphoma, and gave new insights in to the molecular pathways playing a role in this lymphoma.
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PMID:Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas. 1592 May 42

Primary mediastinal large B-cell lymphoma represents a distinct entity with unique clinicopathologic features and a molecular gene-expression signature reminiscent of nodular sclerosis subtype of classical Hodgkin's lymphoma. Recent studies, including those using a refined molecular signature, suggest that the outcome is more favorable than that of diffuse large B-cell lymphoma. Using historical comparisons, dose-dense and dose-intensive regimens may be more effective than cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy; however, the impact of adding rituximab to these regimens and effect on outcome comparisons is unknown. Clinical trials exploring these questions in addition to the benefit of consolidative radiotherapy are necessary to definitively answer these questions.
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PMID:Primary mediastinal large B-cell lymphoma. 1672 Aug 49

Primary mediastinal large B-cell lymphoma (PMLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that is difficult to distinguish from other types of DLBCL on the basis of histologic features alone. We recently identified a molecular signature of PMLBCL that is distinct from other forms of DLBCL but shares features with classical Hodgkin lymphoma. This signature includes activation of the nuclear factor kappaB (NFkappaB) signaling pathway, which in part, acts through nuclear translocation of c-Rel containing NFkappaB transcriptional complexes, and subsequent expression of NFkappaB target genes such as tumor necrosis factor receptor-associated factor-1 (TRAF1). Using standard immunohistochemical techniques, we examined 251 large B-cell lymphomas (78 cases of PMLBCL and 173 cases of other types of DLBCL) to determine whether the expression patterns of c-Rel and TRAF1 could reliably distinguish between PMLBCL and other types of DLBCL. Robust nuclear c-Rel was present in 31 of 48 (65%) cases of PMLBCL and 28 of 160 (18%) cases of DLBCL. In addition, cytoplasmic TRAF1 expression was seen in 48 of 78 (62%) cases of PMLBCL, but only 20 of 173 (12%) cases of DLBCL. Finally, the combined expression of nuclear c-Rel and TRAF1 was seen in 24 of 45 cases (53%) of PMLBCL, but in only 3 of 156 cases (2%) of other types of DLBCL. Thus, the combined nuclear localization of c-Rel and the cellular expression of TRAF1 is a highly specific (specificity=98%) means to distinguish PMLBCL from DLBCL that is readily applicable to routine surgical pathology practice.
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PMID:Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. 1719 26

Primary mediastinal large B-cell lymphoma (PMLBCL) is a unique type of B-cell lymphoma probably arising from a putative thymic medulla B-cell. It constitutes 6-10% of all diffuse large B-cell lymphomas (DLBCL), occurring more often in young females. PMLBCL is characterized by a diffuse proliferation of medium to large B-cells associated with sclerosis and a degree of compartmentalisation. Its main molecular characteristics include: gains in 9p segments, p53 mutations, BCL-2 and MAL gene over-expression, somatic mutations of IgVH genes, BCL-6, PIM-1, PAX-5, RhoH/TTF, and c-MYC, and constitutional NF-kappaB activation. The gene expression signature of PMLBCL seems to be much closer to classic Hodgkin lymphoma than to DLBCL. PMLBCL is characterized by a locally invasive anterior mediastinal mass, often producing cough, chest pain, dyspnea, and superior vena cava syndrome. Most PMLBCL patients have stage I-II, bulky disease, with pleural or pericardial effusions in a third of cases. Systemic symptoms, mainly fever or weight loss, are present in <20% of cases; increased LDH levels are observed in 70-80% of cases. Treatment with CHOP regimen followed by radiation therapy was associated with a 5-year survival of 65%. Apparently better results have been reported with third-generation weekly alternating regimens followed by radiation therapy. Any recurrence is almost always seen in the first 2 years of follow-up, and distant relapses tend to involve extranodal organs. Features associated with poor prognosis are poor performance status, pericardial effusion, bulky disease, high serum LDH at diagnosis, and a compromised dose-intensity of anthracycline and cyclophosphamide.
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PMID:Primary mediastinal large B-cell lymphoma. 1877 28

Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, which has distinct clinical and molecular features, many of which are similar to that of nodular sclerosing/classical Hodgkin lymphoma. Anthracycline-based chemotherapy forms the foundation for treatment of this lymphoma. This review will discuss controversial topics that warrant further study, such as the superiority of third generation regimens over CHOP-based regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone), the use of involved field radiotherapy, and the assessment of clinical response by positron emission tomography scans.
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PMID:Primary mediastinal large B-cell lymphoma. 1936 54

Primary mediastinal large B-cell lymphoma (PMBCL) has a characteristic clinical presentation, morphology, and immunophenotype, representing a clinically favorable subgroup of diffuse large B-cell lymphoma (DLBCL). By gene expression profiling (GEP), PMBCL shares features with classical Hodgkin lymphoma (cHL). Of further interest, BCL6 gene mutations and BCL6 and/or MUM1 expression in a number of PMBCLs have supported an activated B-cell (ABC) origin. Several studies, including GEP, have failed to detect BCL2 gene rearrangements (GRs) in PMBCL. An index case of t(14; 18)+ PMBCL prompted our study of the incidence of BCL2 GRs in PMBCL by polymerase chain reaction (PCR)/fluorescence in situ hybridization (FISH) analyses and its possible clinical impact. Twenty-five retrospectively identified, well-defined PMBCLs (five with cytogenetics) from three institutions were analyzed for a BCL2 GR by PCR/FISH analyses. The formalin-fixed, paraffin-embedded tissue blocks of 24 available cases were also analyzed by BCL2 immunohistochemistry (IHC). Of the five with cytogenetics, two had a t(14; 18) (q32; q21). Of the 25 analyzed by PCR, 2 had no amplifiable DNA (aDNA), including 1 t(14; 18)+ case. Of those with aDNA, two showed a BCL2 GR; by FISH analysis, three demonstrated a BCL2 GR. BCL2 protein expression by IHC analysis was variably detected in 21 out of 24 (strongly, uniformly expressed: 6, including all with a t(14; 18) or a BCL2 gene rearrangement; moderately weakly expressed in a subset of the malignant cells: 15). Available clinical follow-up of this BCL2+ subset showed a similar course to the other PMBCL cases. Our results imply that a subset of PMBCL [(4 out of 24 analyzed) in our series] may be of GC origin. A larger study is necessary to determine any clinical significance.
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PMID:Primary mediastinal B-cell lymphoma: detection of BCL2 gene rearrangements by PCR analysis and FISH. 1966 6

The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.
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PMID:T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma. 2038 9

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of lymphoma that shares similarities with diffuse large B-cell lymphoma and with classic Hodgkin's lymphoma. The current study evaluates the use of autologous stem cell transplant (ASCT) as part of initial therapy in a cohort of patients with PMBCL treated between 1985 and 2006. The study demonstrates excellent survival and progression-free survival for patients in complete remission (CR) at ASCT, and for those achieving CR after ASCT. It also shows a benefit to administration of involved-field radiation therapy. However, front-line therapy has evolved considerably since these patients were treated. Dose-dense chemotherapy regimens show excellent results without transplant and the incorporation of rituximab in the treatment may have further improved outcomes. Given these excellent results, ASCT should not currently be used in patients in first CR, but ASCT remains the treatment of choice in relapsed and refractory PMBCL. Similarly, radiotherapy is unnecessary in patients in first CR but is probably useful in patients with residual active mass.
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PMID:Autologous transplant for primary mediastinal B-cell lymphoma. 1843 30

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) accounting for 2% to 4% of all non-Hodgkin lymphomas. We report a family of 3 siblings with PMBCL and their cousin with extranodal DLBCL. The histopathological characteristics of lymphomas of all 4 patients are similar, implying post-germinal center differentiation and growth deregulation by other mechanisms than BCL2-mediated inhibition of apoptosis and suggesting a shared biological background. We aimed to identify the genetic defect underlying lymphoma susceptibility in this family using exome sequencing and linkage analysis. The only variant segregating in all 4 patients and not reported in genetic databases was 5533C>A (His1845Asn) in the MLL gene. To our knowledge, this is the first time when familial clustering of PMBCL is reported. Although we propose MLL as a candidate predisposition gene for this condition, this finding needs to be validated in additional cases.
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PMID:Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene. 2345 95


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