Case 3 -
Transformation of CLL into a Diffuse Large B Cell Lymphoma with Anaplastic Morphology and a HL Component
University of Groningen
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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
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
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.
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.
- 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.