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

摘要: 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 cells varying degrees nuclear polymorphism clear to basophilic cytoplasm. On immunohistochemistry, following phenotype 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−, CD3−. Immunoglobulins were negative both at immunohistochemistry in situ hybridization. Molecular analysis, performed 45 cases, showed novel findings. More than half displayed BCL-6 gene mutations, which usually occurred along functioning somatic IgVH mutations Bcl-6 and/or MUM1/IRF4 expression. present study supports concept sizable fraction this from activated germinal center or postgerminal cells. However, it differs other aggressive lymphomas shows defective immunoglobulin production despite expression OCT-2, BOB.1, PU.1 transcription factors lack crippling mutations.