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

Stefano A. Pileri, Gianluca Gaidano, Pier Luigi Zinzani, Brunangelo Falini, Philippe Gaulard, Emanuele Zucca, Federica Pieri, Eva Berra, Elena Sabattini, Stefano Ascani, Milena Piccioli, Peter W M Johnson, Roberto Giardini, Edoardo Pescarmona, Domenico Novero, Pier Paolo Piccaluga, Teresa Marafioti, Miguel A. Alonso, Franco Cavalli

Research output: Contribution to journalArticlepeer-review

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 IgVH 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 IgVH gene crippling mutations.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalAmerican Journal of Pathology
Volume162
Issue number1
Publication statusPublished - Jan 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this