title: The immunophenotypic spectrum of primary mediastinal large B-cell lymphoma reveals prognostic biomarkers associated with outcome.
abstract: Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) that shows overlap with classical Hodgkin lymphoma (CHL) and a favorable prognosis compared to mediastinal gray-zone lymphoma (MGZL). We performed immunohistochemistry on initial diagnostic specimens of 49 cases of uniformly treated PMBL to determine the frequency and clinical significance of expression of antigens commonly seen in CHL and MGZL, along with markers previously shown to be prognostic in DLBCL, not otherwise specified. The median age was 37 years with a female:male ratio of 2.3. After a median follow-up of 78 months, 24% of patients had relapsed or refractory disease and 22% had died; the 5-year PFS was 70%. Variable CD15 expression was seen in 31% of cases, but was not associated with adverse outcome. Hans cell-of-origin, proliferation index, and MYC/BCL2 coexpression were not associated with outcome, while low PDL1 (P = 0.011) and high MUM1 (P = 0.065) staining were each associated with shorter PFS. A biologic risk score (one point each for low PDL1 and high MUM1) stratified patients into three prognostic risk groups for PFS (P = 0.001) and OS (P = 0.032). On separate multivariate models, low PDL1 was independent of R-IPI risk group for PFS (HR 6.0, P = 0.023), as was a biologic risk score of 2 (HR 5.6, P = 0.011). Incorporation of the biologic risk score sub-stratified patients within R-IPI groups for both PFS (P < 0.001) and OS (P < 0.001). In summary, we characterize the immunophenotypic spectrum of PMBL and identify PDL1 and MUM1 as prognostic biomarkers for high-risk disease. Am. J. Hematol. 91:E436-E441, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Bledsoe
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Redd
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
authors.affiliation: Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Soumerai
authors.affiliation: Department of Pathology, North Shore Medical Center, Salem, Massachusetts.
authors.forename: Ha T
authors.initials: HT
authors.lastname: Nishino
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Boyer
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Zukerberg
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Nancy Lee
authors.initials: NL
authors.lastname: Harris
authors.affiliation: Center for Lymphoma, Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Abramson
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. arsohani@partners.org.
authors.forename: Aliyah R
authors.initials: AR
authors.lastname: Sohani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D050835:Interferon Regulatory Factors / Q000032:analysis*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008479:Mediastinal Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4; C423236:CD274 protein, human