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(American Journal of Pathology. 2003;162:243-253.)
© 2003 American Society for Investigative Pathology

Regular Articles

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 and Franco Cavalli^¶ (on behalf of the International Extranodal Lymphoma Study Group)

From the Istituto di Ematologia e Oncologia Medica,^*"L. e A. Seràgnoli" Unità Cliniche e di Anatomia Patologica, Università di Bologna, Bologna, Italy; the Dipartimento di Scienze Mediche,Divisione di Medicina Interna, Unitá Didattica di Assistenza Ematologia, the Università del Piemonte Orientale "Amedeo Avogadro," Novara, Italy; the Cattedra di Ematologia,Laboratorio di Emopatologia, Università di Perugia, Perugia, Italy; the Divisione di Anatomia Patologica,^**Istituto Nazionale dei Tumori, Milano, Italy; the Dipartimento di Patologia,Sezione di Immunopatologia, Università di Roma "La Sapienza," Roma, Italy; the Istituto di Anatomia Patologica,Università di Torino, Torino, Italy; the Department de Pathologie,Hopital Henri Mondor, Creteil, France; Istituto Oncologico della Svizzera Italiana,^¶Ospedale S. Giovanni, Bellinzona, Switzerland; the Wessex Medical Oncology Unit,^||Southampton University, Southampton, United Kingdom; and Centro de Biologia Molecular "Severo Ochoa,"Universidad Autonoma de Madrid, Madrid, Spain

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.

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