title: Clonal T-cell populations and increased risk for cytotoxic T-cell lymphomas in B-CLL patients: clinicopathologic observations and molecular analysis.
abstract: Chronic lymphocytic leukemia (CLL) is associated with increased risk of malignancy, but the occurrence of other lymphomas, in particular T-cell lymphomas, is rare. We identified 7 cases of peripheral T-cell malignancy associated with B-cell-derived CLL from the files of two institutions over a 20-year period. The presence of both B and T lymphoproliferative disorders was confirmed in all cases by immunophenotype and in 6 cases by gene rearrangements. Six patients developed peripheral T-cell lymphoma (PTCL), unspecified, during the course of CLL (10-168 months). In all 5 evaluable cases, the cells had a cytotoxic T-cell phenotype; the sixth case was CD56+, but TIA-1 and Granzyme B could not be studied. A seventh patient with CLL developed mycosis fungoides, and an aggressive NK cell leukemia. To investigate possible risk factors for the development of PTCL, we screened 100 unselected peripheral blood samples from newly diagnosed CLL patients by PCR for the presence of clonal T cell populations. We found evidence of clonal T-cell expansion in 8 patients and increased lymphocytes with large granular lymphocyte morphology in 7 of 8 cases. The immunophenotype was assessed by multicolor flow cytometry and in 4 cases the T-cell expansion was composed of either CD3+/CD8+ or CD3+/CD4-/CD8- cells. The cytotoxic nature of the clonal T-cell expansions in the peripheral blood correlates with the cytotoxic nature of the PTCLs, but their role in the subsequent development of T-cell lymphomas is still unclear. PTCL following CLL should be distinguished from typical Richter syndrome, which it can mimic clinically.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Maria
authors.initials: M
authors.lastname: Rozman
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000368:Aged; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens