title: A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases.
abstract: Most primary central nervous system lymphomas (PCNSLs) in immunocompetent patients are diffuse large B-cell lymphomas (DLBCLs), characterized by poor prognosis, compared with systemic forms. A germinal center B-cell-like (GCB) origin of PCNSL was hypothesized on the basis of BCL-6 expression and ongoing mutational activity. Our goal herein was to determine, for 83 PCNSLs, the percentages of GCB and activated B-cell-like (ABC) phenotypes and their prognostic significance. CD10, BCL-6, MUM1, BCL-2, and CD138 antigens were immunohistochemically labeled on paraffin-embedded sections; the first 4 were positive in 2.4%, 55.5%, 92.6%, and 55.5% of the tumors, respectively. None of the 56 tested samples expressed CD138. Among the 82 patients with complete information, 79 (96.3%) were classified as ABC; 42 (51.2%) expressed BCL-6+ MUM1+, suggesting an "activated GCB" origin; 33 (40.2%) were exclusively MUM1+, and the remaining 4 (4.9%) were negative for all markers tested. These findings provide new insights into interpreting the poor PCNSL prognostic, which may, in part, be due to biologic aggressiveness associated with its activated B-cell-like pattern. We postulate assigning PCNSL a histogenetic "time-slot," overlapping late GC and early post-GC, that could explain the predominant ABC phenotype observed.
authors.affiliation: Université Paris-Descartes, Faculté de médecine, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France. sophie.camilleri-broet@htd.ap-hop-paris.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Crinière
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Vincent
authors.initials: V
authors.lastname: Delwail
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Anne
authors.initials: A
authors.lastname: Moreau
authors.forename: Michèle
authors.initials: M
authors.lastname: Kujas
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
authors.forename: Wafae
authors.initials: W
authors.lastname: Iraqi
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Philippe
authors.initials: P
authors.lastname: Colombat
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Antoine
authors.initials: A
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000145:classification / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm