A Clinicopathologic Study Of Diffuse Large B-cell Lymphoma With Emphysis On Immunophenotypic Subtypes And Genetic Abnormalities

A clinicopathologic study of diffuse large B-cell lymphoma with emphysis on immunophenotypic subtypes and genetic abnormalitiesLU Jinbiao Tutor: professor ZHU XiongzengObjective: To investigate the clinicopathologic, immunophenotypic and genetic features of diffuse large B-cell lymphoma (DLBCL), with special concern with the difference between nodal and extranodal lesions.Methods: One hundred and forty-two cases of de novo DLBCL were studied. Tissue microarry (TMA) block and section slides were prepared. Clinical characteristics were analyzed. Sections were immunohistochemically stained with antibodies against CD10, Bcl6, MUM1 and Bcl2．Germinal center B-cell (GCB) and non-GCB immunophenotype were then distinguished. The interrelationship between immunophenotype,nodal or extranodal origin and outcome were analyzed. Polymerase chain reaction (PCR) assay was used to detect the t (14; 18) in 75 and 74 cases with frozen tissue and with formalin-fixed tissue, respectively. The status of Bcl6 gene rearrangement was evaluated by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections in 32 cases. Relationship between immunophenotype, sites and the t (14; 18) or Bcl6 rearrangement were also analyzed.Results: Patients with primary gasterointestinal DLBCL mostly presented with early-stage disease and low international prognostic index (IPI), characterized by a better outcome compared with nodal DLBCL. The expression rate of CD10, Bcl6, MUM1, Bcl2 were 19%, 50．7%, 57．7% and 53．5%, respectively. The percentage of GCB type cases and non-GCB type cases were 35．9% and 64．1%, respectively. Extranodal cases featured more frequent Bcl6 expression and GCB immunophenotype compared with nodal lesions. Regarding different extranodal sites, thyroid and breast DLBCL mostly showed the GCB phenotype, whereas testicular DLBCL were mostly non-GCB tumors. Bcl6 expression and GCB phenotype could predict better overall survival (OS), whereas expression of Bcl2 was associated with a worse outcome. The t (14; 18) was detected in 14 of 75 cases using frozen material and in 6 of 74 using paraffin specimens. Correlation of t (14; 18) with CD10 expression rather than Bcl2 expression, GCB phenotype or sites was observed. Bcl6 rearrangement was detected in 6 cases. No relationship was found between Bcl6rearrangement and Bcl6 expression, immunophenotype or sites.Conclusions: Diffuse large B-cell lymphoma can be subclassified into two majorgroups: GCB-DLBCL and non-GCB-DLBCL. GCB cases show better outcome thannon-GCB cases. The primary site of disease was associated with paticular clinical andimmunophenotypic features and prognosis. Neither t (14; 18) nor Bcl6 rearrangementis related to immunophenotype and nodal or extranodal origin.