title: Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium.
abstract: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L
authors: L
authors: Deng
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z Y
authors: ZY
authors: Xu-Monette
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Loghavi
authors: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: G C
authors: GC
authors: Manyam
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Y
authors: Y
authors: Xia
authors: San Bortolo Hospital, Vicenza, Italy.
authors: C
authors: C
authors: Visco
authors: Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea.
authors: J
authors: J
authors: Huh
authors: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L
authors: L
authors: Zhang
authors: Tianjin Medical University Cancer Institute and Hospital, Institute of Hematology, CAMS & PUMC, Tianjin, China.
authors: Q
authors: Q
authors: Zhai
authors: Tianjin Medical University Cancer Institute and Hospital, Institute of Hematology, CAMS & PUMC, Tianjin, China.
authors: Y
authors: Y
authors: Wang
authors: Tianjin Medical University Cancer Institute and Hospital, Institute of Hematology, CAMS & PUMC, Tianjin, China.
authors: L
authors: L
authors: Qiu
authors: Aalborg University Hospital, Aalborg, Denmark.
authors: K
authors: K
authors: Dybkær
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: A
authors: A
authors: Chiu
authors: University of Manitoba, Winnipeg, MB, Canada.
authors: A M
authors: AM
authors: Perry
authors: Indiana University School of Medicine, Indianapolis, IN, USA.
authors: S
authors: S
authors: Zhang
authors: University Hospital, Basel, Switzerland.
authors: A
authors: http://orcid.org/0000-0002-1100-3819
authors: A
authors: Tzankov
authors: Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: H
authors: H
authors: Rao
authors: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: J
authors: J
authors: Abramson
authors: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: A R
authors: AR
authors: Sohani
authors: Yale University School of Medicine, New Haven, CT, USA.
authors: M
authors: M
authors: Xu
authors: Cleveland Clinic, Cleveland, OH, USA.
authors: E D
authors: ED
authors: Hsi
authors: Peking University Cancer Hospital and Institute, Beijing, China.
authors: J
authors: J
authors: Zhu
authors: San Raffaele H Scientific Institute, Milan, Italy.
authors: M
authors: M
authors: Ponzoni
authors: National University Hospital, Singapore, Singapore.
authors: S
authors: S
authors: Wang
authors: The First Affiliated Hospital of Zhengzhou University, Henan, China.
authors: Ling
authors: L
authors: Li
authors: The First Affiliated Hospital of Zhengzhou University, Henan, China.
authors: M
authors: M
authors: Zhang
authors: San Raffaele H Scientific Institute, Milan, Italy.
authors: A J M
authors: AJ
authors: Ferreri
authors: Gundersen Medical Foundation, La Crosse, WI, USA.
authors: B M
authors: BM
authors: Parsons
authors: Cleveland Clinic, Cleveland, OH, USA.
authors: Y
authors: Y
authors: Li
authors: Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors: M A
authors: MA
authors: Piris
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L J
authors: LJ
authors: Medeiros
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, TX, USA.
authors: K H
authors: KH
authors: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012008:Recurrence; D012097:Repressor Proteins / Q000032:analysis; D000069283:Rituximab / Q000627:therapeutic use*; D013736:Testicular Neoplasms / Q000188:drug therapy*
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C090851:TCL1A protein, human; D000069283:Rituximab