title: Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins.
abstract: Although primary mediastinal (thymic) large B-cell lymphoma has been primarily studied, its precise phenotype, molecular characteristics, and histogenesis are still a matter of debate. The International Extranodal Lymphoma Study Group collected 137 such cases for extensive pathological review. Histologically, the lymphomatous growth was predominantly diffuse with fibrosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. On immunohistochemistry, the following phenotype was observed: CD45(+), CD20(+), CD79a(+), PAX5/BSAP(+), BOB.1(+), Oct-2(+), PU.1(+), Bcl-2(+), CD30(+), HLA-DR(+), MAL protein(+/-), Bcl-6(+/-), MUM1/IRF4(+/-), CD10(-/+), CD21(-), CD15(-), CD138(-), CD68(-), and CD3(-). Immunoglobulins were negative both at immunohistochemistry and in situ hybridization. Molecular analysis, performed in 45 cases, showed novel findings. More than half of the cases displayed BCL-6 gene mutations, which usually occurred along with functioning somatic IgV(H) gene mutations and Bcl-6 and/or MUM1/IRF4 expression. The present study supports the concept that a sizable fraction of cases of this lymphoma are from activated germinal center or postgerminal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective immunoglobulin production despite the expression of OCT-2, BOB.1, and PU.1 transcription factors and the lack of IgV(H) gene crippling mutations.
authors.affiliation: Istituto di Ematologia e Oncologia Medica, L. e A. Seràgnoli Unità Cliniche e di Anatomia Patologica, Università di Bologna, Bologna, Italy. pileri@almadns.unibo.it
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Federica
authors.initials: F
authors.lastname: Pieri
authors.forename: Eva
authors.initials: E
authors.lastname: Berra
authors.forename: Elena
authors.initials: E
authors.lastname: Sabattini
authors.forename: Stefano
authors.initials: S
authors.lastname: Ascani
authors.forename: Milena
authors.initials: M
authors.lastname: Piccioli
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Johnson
authors.forename: Roberto
authors.initials: R
authors.lastname: Giardini
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.forename: Domenico
authors.initials: D
authors.lastname: Novero
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalli
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D005787:Gene Frequency; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency* / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C091546:POU2AF1 protein, human; C058435:POU2F2 protein, human