Myotropic Th1 T helper cell lymphoma presenting as granulomatous inflammatory masses in synovium and muscle

Human T helper (Th) lymphocyte subsets can be differentiated by cytokine production; Thl cells produce inteferon-gamma and interleukin-2, while Th2 cells produce interleukin-4 and interleukin-5. Imbalance of Th subsets leads to disordered immunity and a myriad of disease manifestations. We identified a patient with an unusual syndrome of masses of granulomatous tissue in synovium and muscle that was initially diagnosed as pigmented villonodular synovitis. We examined primary (1988) and recurrent (1994) lesions from this patient for T cell receptor (TCR) variable (V)p gene usage and cytokine mRNA expression using reverse transcription (RT) polymerase chain reaction (PCR) and sequence analysis. Patient lesions contained numerous macrophage-derived multinucleated giant cells, CD4+ T helper cells, and biased TCR Vβ repertoires with two overrepresented TCR Vβ families present. Southern blot and sequence analysis showed these infiltrating T cells to be clonal. Analysis of cytokine mRNA expression in patient tissue showed elevated expression of Thl cytokine mRNA (interferon-gamma, interleukin-2). Karyotype analysis of patient tissue infiltrating T cells demonstrated a 1:9 chromosomal translocation. Study of two PVNS tissues and giant cell tumor of bone, with histologies similar to our patient, did not reveal clonal T cell proliferations, karyotype abnormalities, or overexpression of interferon-gamma mRNA. These studies describe a novel syndrome of a myotropic Thl T helper cell lymphoma, in which overproduction of the Thl cytokine, gamma-interferon, likely resulted in massive macrophage-derived giant cell formation. Moreover, these studies demonstrate that molecular analysis of lesional tissues of patients with granulomatous infiltrative diseases can play an important role in accurate diagnosis and treatment.

Duke Scholars

Author Nancy Bates Allen Medicine, Rheumatology and Immunology

Author Blythe Hazlehurst Devlin Pediatrics, Allergy and Immunology

Author Russel E. Kaufman Medicine, Medical Oncology

Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute