Transformation in lymphomas--morphological, immunophenotypic and molecular features.

During the course of lymphoma, a clinically more aggressive process with different morphology may develop, referred to as lymphoma transformation. Clonal relationship and pathogenic mechanism of this process are widely debated. The aim of the study was to evaluate morphology, immunophenotype (including EBV status) and clonal relationship in nine cases of lymphoma transformation. Among the six patients with low grade B-cell lymphomas three transformed into high grade B-cell lymphomas (two into diffuse large B-cell lymphoma, one into Burkitt lymphoma) and three into Hodgkin lymphoma. Three other patients with Hodgkin lymphoma presented with transformation into diffuse large B-cell lymphoma in two patients and peripheral T-cell lymphoma in one patient. In all cases there was a sudden clinical change as well as change in morphology and phenotype. In five of the nine patients studied EBV-LMP1 was demonstrated by immunohistochemistry in large transformed lymphoma cells. In two cases molecular studies revealed a different pattern of immunoglobulin gene rearrangement in the large transformed cells as compared to the small cells of primary indolent lymphoma. Thus, they represented secondary, arising de novo neoplasm.