title: Flow Cytometric Evaluation of Double/Triple Hit Lymphoma.
abstract: "Double" or "triple" hit lymphomas (D/THL) with recurrent translocations involving MYC/8q24 and BCL2/18q21 and/or BCL6/3q27 are characterized by a poor prognosis, but their identification is hampered by the clinicopathologic overlap with other disease categories. Cases with circulating blastic-appearing cells may initially cause concern for lymphoblastic leukemia a diagnostic dilemma, which has not been well studied. There is only limited literature regarding the flow cytometric (FC) D/THL phenotype and its clinical correlates. The FC features of 20 D/THL (11 BCL2(+)/MYC(+), 5 BCL6(+)/MYC(+), 4 BCL2(+)/BCL6(+)/MYC(+)) were evaluated, compared to 20 B-lymphoblastic leukemias (B-LBL), and correlated with overall survival. Most (89%, 17/19) D/THL were CD10(+), 47% (9/19) lacked surface light chain, and a significant subset underexpressed CD45 (47%, 9/19), CD20 (42% 8/19), and/or CD19 (39%, 7/18), which did not vary by genetic subgroup. Compared to B-LBL, D/THL less frequently underexpressed CD45 (p = 0.0001) and CD20 (p = 0.0004). Lower levels of BCL2 expression were noted in the BCL6(+)/MYC(+) and BCL2(+)/BCL6(+)/MYC(+) subgroups versus BCL2(+)/MYC(+) cases (p = 0.0014). Of the flow cytometric parameters assessed, dim CD45 expression correlated with inferior survival (p = 0.01). Although there is some overlap with B-LBL, D/THL demonstrates a characteristic immunophenotype which may have prognostic significance and warrants further investigation.
authors.affiliation: Department of Pathology, Division of Hematopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Roth
authors.forename: Amanda
authors.initials: A
authors.lastname: Gillespie-Twardy
authors.forename: Stanley
authors.initials: S
authors.lastname: Marks
authors.forename: Mounzer
authors.initials: M
authors.lastname: Agha
authors.forename: Anastasios
authors.initials: A
authors.lastname: Raptis
authors.forename: Jing-Zhou
authors.initials: JZ
authors.lastname: Hou
authors.forename: Rafic
authors.initials: R
authors.lastname: Farah
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Qian
authors.forename: Liron
authors.initials: L
authors.lastname: Pantanowitz
authors.forename: Michael
authors.initials: M
authors.lastname: Boyiadzis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000276:immunology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; C084103:BCL6 protein, human; C000604811:CD19 molecule, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human