Pileri Stefano A, Gaidano Gianluca, Zinzani Pier Luigi, Falini Brunangelo, Gaulard Philippe, Zucca Emanuele, Pieri Federica, Berra Eva, Sabattini Elena, Ascani Stefano, Piccioli Milena, Johnson Peter W M, Giardini Roberto, Pescarmona Edoardo, Novero Domenico, Piccaluga Pier Paolo, Marafioti Teresa, Alonso Miguel A, Cavalli Franco
Istituto di Ematologia e Oncologia Medica, L. e A. Seràgnoli Unità Cliniche e di Anatomia Patologica, Università di Bologna, Bologna, Italy.
Am J Pathol. 2003 Jan;162(1):243-53. doi: 10.1016/s0002-9440(10)63815-1.
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.
尽管原发性纵隔（胸腺）大B细胞淋巴瘤已得到主要研究，但其确切的表型、分子特征和组织发生仍存在争议。国际结外淋巴瘤研究组收集了137例此类病例进行广泛的病理复查。组织学上，淋巴瘤生长主要呈弥漫性伴纤维化，导致细胞呈分隔状聚集。它由具有不同程度核多形性和透明至嗜碱性细胞质的大细胞组成。免疫组化观察到以下表型：CD45(+)、CD20(+)、CD79a(+)、PAX5/BSAP(+)、BOB.1(+)、Oct-2(+)、PU.1(+)、Bcl-2(+)、CD30(+)、HLA-DR(+)、MAL蛋白(+/-)、Bcl-6(+/-)、MUM1/IRF4(+/-)、CD10(-/+)、CD21(-)、CD15(-)、CD138(-)、CD68(-)和CD3(-)。免疫球蛋白在免疫组化和原位杂交中均为阴性。对45例病例进行的分子分析显示了新的发现。超过一半的病例显示BCL-6基因突变，这些突变通常与功能性体细胞IgV(H)基因突变以及Bcl-6和/或MUM1/IRF4表达同时发生。本研究支持这样一种观点，即该淋巴瘤相当一部分病例源自活化的生发中心或生发中心后细胞。然而，它与其他侵袭性B细胞淋巴瘤不同，尽管表达了OCT-2、BOB.1和PU.1转录因子且缺乏IgV(H)基因致残突变，但它仍显示免疫球蛋白产生缺陷。
