Case 3 -

Transformation of CLL into a Diffuse Large B Cell Lymphoma with Anaplastic Morphology and a HL Component Sibrand Poppema University of Groningen Groningen, Netherlands

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Clinical history: A 76 year old male, who was diagnosed with chronic lymphocytic leukemia (CLL) three years earlier, developed rapidly enlarging lymph nodes. A lymph node biopsy showed a composite lymphoma with areas of CLL, areas of large cell lymphoma with anaplastic morphology, and areas with Hodgkin lymphoma (HL) histology. Case 3 - Figure 1 H&E, 40x Case 3 - Figure 2 H&E, 40x Case 3 - Figure 3 H&E, 40x The differential diagnosis obviously circles around the question whether this is one lymphoma with different transformations or whether these are two or even three different (collision) lymphomas. Large cell lymphoma and HL may develop during the course of chronic lymphocytic leukemia. In some cases the transformed cells are Epstein-Barr virus (EBV) positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (RS) cells in the HL component also strongly express TIA-1 but differ from the diffuse large cell component by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The diffuse large cell and the HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated RS cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell lymphoma components. Final diagnosis: The findings indicate transformation of CLL into a diffuse large B cell lymphoma with anaplastic morphology and a HL component. This case is an example of the immunophenotypic aberrations in RS cells: immunoglobulin gene rearrangements with loss of most B cell markers and expression of myeloid markers like CD15, dendritic cell markers like TARC and sometimes cytotoxic granule markers like TIA-1. It is of interest that the expression of TARC coincides with the presence of a prominent lymphocytic infiltrate. Reference : van den Berg A, Maggio E, Rust R, Kooistra K, Diepstra A, Poppema S. Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma. Blood. 2002, 100:1425-1429.