Characteristics of T-cell large granular lymphocyte proliferations associated with neutropenia and inflammatory arthropathy
1 Department of Pathomorphology, Institute of Hematology and Transfusion Medicine, I. Gandhi 14, 02-776 Warsaw, Poland
2 Department of Pathology, Institute of Rheumatology, Spartańska 1, 02-637 Warsaw, Poland
3 Department of Pathology, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
4 Molecular Biology Laboratory, Institute of Hematology and Transfusion Medicine, I. Gandhi 14, 02-776 Warsaw, Poland
5 Department of Internal Diseases and Hematology, Institute of Hematology and Transfusion Medicine, I. Gandhi 14, 02-776 Warsaw, Poland
6 Department of Rheumatology, Institute of Rheumatology, Spartańska 1, 02-637 Warsaw, Poland
7 Department of Hematology, Institute of Hematology and Transfusion Medicine, I. Gandhi 14, 02-776 Warsaw, Poland
Arthritis Research & Therapy 2008, 10:R55 doi:10.1186/ar2424Published: 12 May 2008
The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with no arthritis symptoms.
Clinical, serological as well as histopathological, immuhistochemical, and flow cytometric evaluations of blood/bone marrow of 21 patients with T-LGL lymphocytosis were performed. The bone marrow samples were also investigated for T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangements by polymerase chain reaction with heteroduplex analysis.
Neutropenia was observed in 21 patients, splenomegaly in 10, autoimmune diseases such as rheumatoid arthritis (RA) in 9, unclassified arthritis resembling RA in 2, and autoimmune thyroiditis in 5 patients. T-LGL leukemia was recognized in 19 cases. Features of Felty syndrome were observed in all RA patients, representing a spectrum of T-LGL proliferations from reactive polyclonal through transitional between reactive and monoclonal to T-LGL leukemia. Bone marrow trephines from T-LGL leukemia patients showed interstitial clusters and intrasinusoidal linear infiltrations of CD3+/CD8+/CD57+/granzyme B+ lymphocytes, reactive lymphoid nodules, and decreased or normal granulocyte precursor count with left-shifted maturation. In three-color flow cytometry (FCM), T-LGL leukemia cells demonstrated CD2, CD3, and CD8 expression as well as a combination of CD16, CD56, or CD57. Abnormalities of other T-cell antigen expressions (especially CD5, CD7, and CD43) were also detected. In patients with polyclonal T-LGL lymphocytosis, T cells were dispersed in the bone marrow and the expression of pan-T-cell antigens in FCM was normal. Molecular studies revealed TCRB and TCRG gene rearrangements in 13 patients and TCRB, TCRG, and TCRD in 4 patients. The most frequently rearranged regions of variable genes were Vβ-Jβ1, Jβ2 and Vγ If Vγ10-Jγ. Moreover, in 4 patients, additional rearrangements of IG kappa and lambda variable genes of B cells were also observed.
RA and neutropenia patients represented a continuous spectrum of T-LGL proliferations, although monoclonal expansions were most frequently observed. The histopathological pattern and immunophenotype of bone marrow infiltration as well as molecular characteristics were similar in T-LGL leukemia patients with and without arthritis.