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Primary mediastinal lymphoma

Sanghoon Lee, Tishi Shah, Changhong Yin, Jessica Hochberg, Janet Ayello, Erin Morris, Carmella van de Ven, Mitchell S Cairo
Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBL) share similar molecular features by gene expression profiling. Frequent gains of chromosome 9p exhibit higher Janus Kinase 2 (JAK2) transcript levels with increased JAK2 activity, suggesting aberrant activity of JAK2 and STAT pathways. This signaling pathway alteration may in part play an important role in the pathogenesis and/or chemoradiotherapy resistance in HL and PMBL. Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor, with activity against myeloproliferative neoplasms (MPNs) including those harboring the JAK2V617F mutation...
February 9, 2018: Oncotarget
Hadjer Miloudi, Karen Leroy, Fabrice Jardin, Brigitte Sola
Primary mediastinal B-cell lymphoma (PMBL) is a distinct B-cell lymphoma subtype with unique clinicopathological and molecular features. PMBL cells are characterised by several genetic abnormalities that conduct to the constitutive activation of the Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signalling pathway. Among recurrent genetic changes in PMBL, we previously reported that the XPO1 gene encoding exportin 1 that controls the nuclear export of cargo proteins and RNAs, is mutated (p...
March 1, 2018: Cellular Signalling
Elena Viganò, Jay Gunawardana, Anja Mottok, Tessa Van Tol, Katina Mak, Fong Chun Chan, Lauren Chong, Elizabeth Chavez, Bruce Woolcock, Katsuyoshi Takata, David Twa, Hennady P Shulha, Adèle Telenius, Olga Kutovaya, Stacy S Hung, Shannon Healy, Susana Ben-Neriah, Karen Leroy, Philippe Gaulard, Arjan Diepstra, Robert Kridel, Kerry J Savage, Lisa Rimsza, Randy Gascoyne, Christian Steidl
Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 out of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8 leading to an I242N amino acid change in the transmembrane domain...
February 21, 2018: Blood
Irit Avivi, Ariane Boumendil, Hervé Finel, Arnon Nagler, Aïda Botelho de Sousa, Josep Maria Ribera Santasusana, Elizabeth Vandenberghe, Boris Afanasyev, Dominique Bordessoule, José Maria Moraleda, Eulogio Conde Garcia, David Pohlreich, Gonzalo Gutiérrez Garcia, Kirsty Thomson, Reuven Or, Dietrich Beelen, Eliana Zuffa, Sebastian Giebel, Christian Berthou, Gilles Salles, Angela Melpignano, Silvia Montoto, Peter Dreger
The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT...
February 20, 2018: Bone Marrow Transplantation
A Mansuet-Lupo, F Lococo, F Larousserie, M Alifano, R Saliceti
Mediastinal tumors are heterogeneous and the diagnosis depends on their location in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and thymoma. The clinical and radiological aspects are often not sufficient to orient the diagnosis and biopsy is necessary to confirmed it. Here, we present a rare case of an anterior mediastinal mass incidentally detected in a 63 years old man during assessment for asthma. The lesion was presumptively diagnosed as a thymic epithelial tumor based on location and radiological characteristics...
December 2017: Pathologica
Xiao-Dong Zhang, Li-Ming He, Lei Ma, Zhang-Guo Chang
OBJECTIVE: To explore the relevance between the expression of C-MYC gene and protein of patients with T lymphoblastic lymphoma and leukemia(T-LBL/ALL) and its effect on the prognosis. METHODS: Paraffin specimens from 60 cases of T-LBL/ALL with detailed follow-up during May 2005 to May 2016 were selected as study group; at same time 20 cases of reactive hyperplasia (RH) of lymphonuedes were selected as control group. The immunohistochemical EnVision method was used to mark the terminal deoxynucleotidyl transferase (TDT), myeloperoxidase (MPO), Ki-67 and C-MYC immune tissue...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Satoshi Tetsumoto, Kaoru Okada, Hideki Nagata, Shigenori Toyota, Satoshi Tanaka, Toshie Niki, Naotoshi Tsuruta, Naozumi Higaki, Takashi Niju, Yoshio Oka, Riichiro Nezu, Toshiyuki Ikeda
The patient was a 54-year-old woman with anaplastic lymphoma kinase-positive stage III B lung cancer. She received 4 courses of carboplatin(CBDCA)plus paclitaxel(PTX)plus bevacizumab(Bev)chemotherapy and crizotinib. Chemotherapy reduced the size of the primary site and mediastinal lymphadenopathy; however, the right supraclavicular and subcarinal lymph nodes were enlarged again during crizotinib treatment. Because it was an oligo-recurrence, we performed radiotherapy for these lymph nodes and changed systemic chemotherapy to alectinib...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yosuke Tanaka, Akiko Miyagi Maeshima, Junko Nomoto, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Dai Maruyama, Kensei Tobinai, Yukio Kobayashi
OBJECTIVES: We aimed at investigating the relationship between Classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programmed cell death 1 and the programmed death ligands (PDLs) network. METHODS: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH)...
January 28, 2018: European Journal of Haematology
Roya Sherkat, Mohammad Reza Sabri, Bahar Dehghan, Hamid Bigdelian, Nahid Reisi, Nooshin Afsharmoghadam, Hamid Rahimi, Narges Rahmanian, Cristoph Klein
RATIONALE: Primary cardiac lymphoma (PLC) is an extremely uncommon malignancy. PCL is more common in secondary immunodeficient patients. In this report, we describe a unique case of PLC who had been diagnosed as a STK4 deficient patient. This case is the first Primary immunodeficiency (PID) patient developing PCL in the world. PATIENT CONCERNS: An eleven-year-old girl, a known case of PID, was referred to the pediatric cardiology department because of chest pain and dyspnea...
December 2017: Medicine (Baltimore)
Reid W Merryman, Philippe Armand, Kyle T Wright, Scott J Rodig
Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ∼70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade...
December 12, 2017: Blood Advances
Monika Pilichowska, Stefania Pittaluga, Judith A Ferry, Jessica Hemminger, Hong Chang, Jennifer A Kanakry, Laurie H Sehn, Tatyana Feldman, Jeremy S Abramson, Athena Kritharis, Francisco J Hernandez-Ilizaliturri, Izidore S Lossos, Oliver W Press, Timothy S Fenske, Jonathan W Friedberg, Julie M Vose, Kristie A Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K Gupta, Randy D Gascoyne, Elaine S Jaffe, Andrew M Evens
Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+ , 83%; PAX5+ , 100%; BCL6+ , 20%; MUM1+ , 100%; CD30+ , 92%; EBV+ , 4%)...
December 12, 2017: Blood Advances
Zachary Wright, Alexander Brown
Autoimmune neutropenia is a rare side effect of nivolumab which may respond to antibody-based therapies.Nivolumab can lead to durable complete remission in primary mediastinal B-cell lymphoma refractory to multiple lines of therapy.
July 25, 2017: Blood Advances
Sattva S Neelapu, Frederick L Locke, Nancy L Bartlett, Lazaros J Lekakis, David B Miklos, Caron A Jacobson, Ira Braunschweig, Olalekan O Oluwole, Tanya Siddiqi, Yi Lin, John M Timmerman, Patrick J Stiff, Jonathan W Friedberg, Ian W Flinn, Andre Goy, Brian T Hill, Mitchell R Smith, Abhinav Deol, Umar Farooq, Peter McSweeney, Javier Munoz, Irit Avivi, Januario E Castro, Jason R Westin, Julio C Chavez, Armin Ghobadi, Krishna V Komanduri, Ronald Levy, Eric D Jacobsen, Thomas E Witzig, Patrick Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, David Chang, Jeff Wiezorek, William Y Go
BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy...
December 28, 2017: New England Journal of Medicine
Kieron Dunleavy
Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct clinicopathologic entity that predominantly affects adolescents and young adults and is more common in female subjects. Although PMBCL is considered to be a subtype of diffuse large B-cell lymphoma, its clinical, morphologic, and biological characteristics overlap significantly with those of nodular sclerosing Hodgkin lymphoma (NSHL). Over the past few years, the shared biology of these 2 entities has been highlighted in several studies, and mediastinal gray zone lymphoma, with features intermediate between PMBCL and NSHL, has been recognized as a unique molecular entity...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Andrea Gallamini, Colette Zwarthoed
In the present article, the authors reviewed the rationale of FDG-PET/CT performed at an interim time point during therapy (iPET), focusing on the transition from standard, anatomical assessment of tumor shrinkage with CT to document a chemotherapy response, to the use of functional imaging with PET to assess chemosensitivity of the individual tumor. The prognostic or predictive role of iPET in different lymphoma subsets has been reviewed, with particular emphasis on early and advanced-stage Hodgkin lymphoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, extranodal natural killer/T-cell lymphoma, and primary mediastinal B-cell lymphoma...
January 2018: Seminars in Nuclear Medicine
Kevin Pelland, Stephanie Mathews, Anitha Kamath, Paul Cohen, S David Hudnall, Claudiu V Cotta, Mina L Xu
AIMS: Mediastinal gray zone lymphoma (MGZL) is a rare entity with morphologic, immunophenotypic, and genetic features intermediate between classic Hodgkin lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). It is challenging to differentiate from CHL and PMBL. A specific dendritic cell gene expression profile can distinguish CHL and MGZL from PMBL. We hypothesized that the dendritic markers fascin and CD123 may be helpful in distinguishing MGZL from CHL and PMBL. We also investigated programmed death-ligand 1 (PD-L1) expression in MGZL, which may have therapeutic significance in this difficulty to treat tumor...
November 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
Poonam K Panjwani, Vivek Charu, Monique DeLisser, Hernan Molina-Kirsch, Yasodha Natkunam, Shuchun Zhao
The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Since efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in over 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases respectively, and PD-L1 but not PD-L2 expression correlated with Epstein Barr Virus in tumor cells...
November 6, 2017: Human Pathology
D Chassard
Over the period 2010-2012, maternal mortality linked to anesthesia accounted for 2% of maternal deaths, with no significant change since 2007-2009. Of the 7 maternal deaths analyzed by the expert committee, anesthetic complications were in 5 cases the main cause of death: 4 attributed to direct causes related to anesthetic procedures during childbirth and 1 to indirect cause in connection with an ENT complication during pregnancy. The anesthetic causes of maternal mortality were for the 2010-2012 period: cardiac arrest under spinal anesthesia during caesarean section, local anesthetic intoxication with unsuccessful resuscitation after cardiac arrest without intralipid administration, acute respiratory distress syndrome in the postpartum period after pulmonary aspiration during caesarean section, cardiac arrest during caesarean section under general anesthesia in a context of non-Hodgkin lymphoma with mediastinal syndrome, unsuccessful endotracheal intubation in a context of cellulitis of the oral cavity floor...
December 2017: Gynecologie, Obstetrique, Fertilite & Senologie
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials...
January 4, 2018: Blood
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