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Double-Hit Lymphoma

Zhihong Hu, L Jeffrey Medeiros, Zi Chen, Weina Chen, Shaoying Li, Sergej N Konoplev, Xinyan Lu, Lan V Pham, Ken H Young, Wei Wang, Shimin Hu
MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy...
October 21, 2016: American Journal of Surgical Pathology
Sheng-Tsung Chang, Shang-Wen Chen, Chung-Han Ho, Chun-Chi Kuo, Seiji Sakata, Kengo Takeuchi, Shih-Sung Chuang
BACKGROUND/PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. METHODS: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. RESULTS: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16...
October 20, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Xuan J Wang, L Jeffrey Medeiros, Carlos E Bueso-Ramos, Guilin Tang, Sa Wang, Yasuhiro Oki, Parth Desai, Joseph D Khoury, Roberto N Miranda, Zhenya Tang, Nishitha Reddy, Shaoying Li
In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Allison Rosenthal, Anas Younes
Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by genetic alterations or protein expression represent a group of high grade B-cell lymphomas with inferior outcomes when treated with standard RCHOP chemotherapy. As a result, intensified induction regimens have been suggested in an effort to improve outcomes. Conclusions to date have largely been drawn from retrospective data although prospective data is slowly starting to emerge. Chemoimmunotherapy refractoriness is problematic and relapse rates are high...
September 30, 2016: Blood Reviews
Marco Lucioni, Emilio Berti, Luca Arcaini, Giorgio A Croci, Aldo Maffi, Catherine Klersy, Gaia Goteri, Carlo Tomasini, Pietro Quaglino, Roberta Riboni, Mariarosa Arra, Elena Dallera, Vieri Grandi, Mauro Alaibac, Antonio Ramponi, Sara Rattotti, Maria Giuseppina Cabras, Silvia Franceschetti, Giulio Fraternali-Orcioni, Nicola Zerbinati, Francesco Onida, Stefano Ascani, Maria Teresa Fierro, Serena Rupoli, Marcello Gambacorta, Pier Luigi Zinzani, Nicola Pimpinelli, Marco Santucci, Marco Paulli
Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL...
September 26, 2016: Cancer Medicine
Gwyneth Soon, Guan Wei Ow, Hian Li Chan, Siok Bian Ng, Shi Wang
Primary cardiac lymphoma (PCL) is a rare extranodal lymphoma that involves only the heart and/or pericardium. Primary cardiac lymphoma is much less common in immunocompetent patients compared with those who are immunosuppressed. Patients with PCL have variable clinical manifestations that may lead to misdiagnosis and delay in treatment. Modern radiologic imaging now allows for earlier detection of these tumors. This study describes the clinical, histologic/cytologic, immunophenotypic, and molecular genetic findings for 3 immunocompetent patients with primary cardiac diffuse large B-cell lymphoma...
October 2016: Annals of Diagnostic Pathology
Mirei Horiuchi, Hoyuri Fuseya, Minako Tsutsumi, Yoshiki Hayashi, Kiyoyuki Hagihara, Hiroshi Kanashima, Takafumi Nakao, Yuko Fukushima, Takeshi Inoue, Takahisa Yamane
Double-hit lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14; 18)(q32;q21)involving BCL2. We report a case of a 38-yearold woman with a 2-month history of abdominaldistention. 18F-FDG PET showed multiple positive systemic lymph nodes, positive peritoneum, and multiple positive intra-abdominal masses. Histopathology results of the cervical lymph node were compatible with double-hit follicular lymphoma(Grade 3A)because fluorescence in situ hybridization(FISH)demonstrated both MYC rearrangement and BCL2 gene fusion...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Jung Yong Hong, Cheolwon Suh, Won Seog Kim
Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL.
2016: F1000Research
Yuan Miao, Shimin Hu, Xinyan Lu, Shaoying Li M D, Wei Wang, L Jeffrey Medeiros, Pei Lin
Follicular lymphoma (FL) with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here we report the clinicopathologic features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were of predominantly low grade, 4 of which had focal (≤ 20%) grade 3 A areas, and 2 cases were of grade 3. All cases were positive for pan B-cell antigens, CD10 and BCL6; 6 cases were positive for BCL2. Ki67 was ≤50% in 6 cases and 90% in one grade 3 case...
August 17, 2016: Human Pathology
Ryota Kurimoto, Katsuhiro Shono, Masahiro Onoda, Kyohei Yamamoto, Akira Yokota
Several reports have suggested an increased risk of malignant lymphoma in patients with rheumatoid arthritis treated with methotrexate (MTX). We herein describe the case of a 71-year-old woman with rheumatoid arthritis who developed MYC/BCL2 double-hit lymphoma associated with MTX therapy. She developed a fever and lymphadenopathies over a 2-week period and had elevated levels of soluble IL-2 receptor. Inguinal lymph node and bone marrow biopsies showed diffuse large B cell lymphoma. Fluorescent in situ hybridization revealed MYC and BCL2 gene rearrangements in her lymphoma cells...
2016: Internal Medicine
Daniel J Landsburg, Marissa K Falkiewicz, Adam M Petrich, Benjamin A Chu, Amir Behdad, Shaoying Li, L Jeffrey Medeiros, Ryan D Cassaday, Nishitha M Reddy, Martin A Bast, Julie M Vose, Kimberly R Kruczek, Scott E Smith, Priyank Patel, Francisco Hernandez-Ilizaliturri, Reem Karmali, Saurabh Rajguru, David T Yang, Joseph J Maly, Kristie A Blum, Weiqiang Zhao, Charles Vanslambrouck, Chadi Nabhan
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy...
July 29, 2016: British Journal of Haematology
Rossella Marullo, Sarah C Rutherford, John P Leonard, Leandro Cerchietti
A subset of diffuse large B-cell lymphomas (DLBCL) harbors concomitant rearrangements of MYC, BCL2 and BCL6 and is characterized by clinical aggressiveness and intrinsic refractoriness to standard chemo-immunotherapy. Commonly identified as "double or triple hit" lymphomas, these diseases represent a therapeutic challenge to chemotherapy-based regimens and likely require a more targeted approach. Herein we summarize the unique biological behavior of double and triple hit lymphomas focusing on the coordinated network of pathways that enable cancer cells to tolerate the oncogenic stress imposed by the co-expression of MYC, BCL2 and BCL6...
September 2016: Cell Cycle
Natalia Testo, Luke C Olson, Shivakumar Subramaniyam, Ty Hanson, Cynthia M Magro
Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma...
October 2016: American Journal of Dermatopathology
Miaoxia He, Keting Chen, Suhong Li, Shimin Zhang, Jianming Zheng, Xiaoxia Hu, Lei Gao, Jie Chen, Xianmin Song, Weiping Zhang, Jianmin Wang, Jianmin Yang
BACKGROUND AND AIMS: Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas...
2016: Journal of Cancer
Michael E Kallen, Serge Alexanian, Jonathan Said, Fabiola Quintero-Rivera
Triple hit lymphomas are a subset of so-called double hit non-Hodgkin lymphomas exhibiting simultaneous gene translocations/disruption of MYC, BCL2, and BCL6; however, their overlapping morphologic features and complex genetic rearrangements can render classification and prognostication vexing. Clinically triple hit lymphomas are thought to demonstrate aggressive behavior, similar to or worse than that of double hit lymphomas. Only rare reports of long term survivors exist and raise the possibility that unidentified morphologic, immunologic, or cytogenetic differences may impart a less adverse prognosis than current literature and opinion may suggest...
June 29, 2016: International Journal of Surgical Pathology
Zi Chen, Shimin Hu
No abstract text is available yet for this article.
February 25, 2016: Blood
Alexandra Clipson, Sharon Barrans, Naiyan Zeng, Simon Crouch, Nicholas F Grigoropoulos, Hongxiang Liu, Sylvia Kocialkowski, Ming Wang, Yuanxue Huang, Lisa Worrillow, John Goodlad, Jenny Buxton, Michael Neat, Paul Fields, Bridget Wilkins, John W Grant, Penny Wright, Hesham Ei-Daly, George A Follows, Eve Roman, A James Watkins, Peter W M Johnson, Andrew Jack, Ming-Qing Du
A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation...
July 2015: Journal of Pathology. Clinical Research
Massimiliano Salati, Vittoria Tarantino, Antonino Maiorana, Stefania Bettelli, Stefano Luminari
Secondary central nervous system involvement is an uncommon event that typically occurs early in the natural history of diffuse large B-cell lymphoma and presents as leptomeningeal dissemination in two-thirds of cases. The prognosis of this event is dismal, and treatment options are meagre. Although major validated risk factors for central nervous system dissemination are clinical, concomitant MYC/BCL2 rearrangements as well as MYC/BCL2 protein expression have been recently associated with an increased risk of this complication...
June 15, 2016: Hematological Oncology
Xuejun Tian, Ashley Pelton, Ali Shahsafaei, David M Dorfman
EZH2, a member of the polycomb protein group, is an important methyltransferase that is overexpressed in various neoplasms. We found that in small cell B-cell lymphomas, EZH2 is expressed in <40% of neoplastic cells, with heterogenous signal intensity. In aggressive B-cell lymphomas, 70-100% of tumor cells were positive for EZH2 expression with high signal intensity, which correlated with a high proliferation rate. We investigated the potential signaling molecules that regulate EZH2 overexpression in aggressive B-cell lymphomas and found that 80% of cases of EZH2-positive diffuse large B-cell lymphoma show high p-ERK1/2 expression (average ~57% tumor cell positivity)...
September 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Shaoying Li, Annapurna Saksena, Parth Desai, Jie Xu, Zhuang Zuo, Pei Lin, Guilin Tang, C Cameron Yin, Adam Seegmiller, Jeffrey L Jorgensen, Roberto N Miranda, Nishitha M Reddy, Carlos Bueso-Ramos, L Jeffrey Medeiros
MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma...
May 19, 2016: Oncotarget
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