Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma.
Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). 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. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). 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 (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.
van den Berg
Anke
A
Department of Pathology and Laboratory Medicine, University and University Hospital Groningen, Groningen, The Netherlands.
Maggio
Ewerton
E
Rust
Renata
R
Kooistra
Klaas
K
Diepstra
Arjan
A
Poppema
Sibrand
S
D000368:Aged; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000032:analysis; D002999:Clone Cells; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016256:Lewis X Antigen / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D009154:Mutation; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000276:immunology; D000074019:T-Cell Intracellular Antigen-1
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D007143:Immunoglobulin Heavy Chains; D016256:Lewis X Antigen; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human