TY - JOUR
T1 - Primary mediastinal B-cell lymphoma
T2 - 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
AU - Pileri, Stefano A.
AU - Gaidano, Gianluca
AU - Zinzani, Pier Luigi
AU - Falini, Brunangelo
AU - Gaulard, Philippe
AU - Zucca, Emanuele
AU - Pieri, Federica
AU - Berra, Eva
AU - Sabattini, Elena
AU - Ascani, Stefano
AU - Piccioli, Milena
AU - Johnson, Peter W M
AU - Giardini, Roberto
AU - Pescarmona, Edoardo
AU - Novero, Domenico
AU - Piccaluga, Pier Paolo
AU - Marafioti, Teresa
AU - Alonso, Miguel A.
AU - Cavalli, Franco
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037222114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037222114&partnerID=8YFLogxK
M3 - Article
C2 - 12507907
AN - SCOPUS:0037222114
VL - 162
SP - 243
EP - 253
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -