Linfomas difusos de grandes células B: estudo histopatológico e imuno-histoquímico

Abstract

Diffuse large B cell lymphomas are the most common subtype of non-Hodgkin s lymphomas, whose clinical, morphological and biological diversity has been recently well characterized. These lesions harbor cromossomial and molecular characteristics that lead to different profiles of genic expression. It indicates that the group represents more than one clinical and pathological entity, with distinct prognosis. Besides the International Prognostic Index, different approaches to assess some possible prognostic differentiation in these patients has been used. The study s aim was to evaluate whether or not immunoblastic morphology and the B-cell differentiaton immunophenotypic profile related to germinal center are anyway conected. The immunophenotypic profile is said to identify prognostically distinct groups as described in studies on cDNA microarray, and its identification is easily performed in routine diagnostic laboratories. The present study included 117 patients who presented with a de novo diffuse large B-cell lymphoma between 2002 and 2004, selected on a basis of availability of histological material. Lymphomas related to HIV infection, or originated from the gastrointestinal tract or from the central nervous system as well as those corresponding to specific subtypes (primary mediastinal lymphoma, intravascular lymphoma and primary effusion lymphoma) were not included in this study. The diagnosis of DLBCL was based on WHO classification s criteria. Patients have been also classified according to the tumor s immunoblastic content. Cases of IBL and cases of the centroblastic polymorphic subtype with immunoblasts amounting to more than 50% were defined as having immunoblastic morphology. Immunohistochemistry was performed on tissue microarray slides to establish the immunophenotypic profile. Immunohistochemical panel included antibodies to B-cell differentiation into germinal center type (CG) and non-germinal center type (pCG), CD10, Bcl-6 and MUM1, besides antibodies to CD20, CD3, CD5, CD30 and cyclin D1. Immunophenotypic profile was discriminated into CG and pCG, based on published criteria. Patients with immunoblastic morphology more frequently than not had a non-GCB phenotype (94% versus 6%). On the other hand, tumors with an immunoblastic morphology were less often bcl-6 positive than any other studied lymphomas (5,9% versus 40%, p=0.005). These findings show that the DLBCL s morphological sub-classification does have a biological meaning, and should not be overlooked in lymphoma classifications. These findings agree with recent evidence indicating different ontogeny for such lymphomas