T-cell large granular lymphocyte leukemia presenting as end-stage renal disease: the diagnostic role of flow-cytometric and clonality analysis of the urine sediment.

A 65-year-old white female patient with normal baseline renal function was referred to our hospital with nonoliguric renal failure requiring hemodialysis after progressive deterioration over the previous 6 months. Her past medical history was remarkable for easy fatigability, weight loss, low-grade fever, hypogammaglobulinemia and mild hepatosplenomegaly manifested over the past 6 years. Several liver and bone marrow biopsies during that period had shown a nonspecific polyclonal T-cell infiltration, and she was administered low-dose steroids for symptomatic relief. Physical examination, laboratory workup and imaging studies at presentation showed pancytopenia, hepatosplenomegaly, large symmetric kidneys with normal cortices and no evidence of obstructive uropathy, aseptic pyuria with neutrophils and lymphocytes and mild proteinuria. On biopsy the renal interstitium was infiltrated by large, granular CD3+CD8+CD56-CD57+ lymphocytes, clonal by molecular analysis, which established the diagnosis of T-cell large granular lymphocyte leukemia. Most urinary and peripheral blood lymphocytes bore the same T-LGL surface markers and were also clonal, as shown by flow-cytometry and PCR amplification of the T-cell receptor g-chain genes. A subsequent bone marrow biopsy revealed infiltration by lymphoma cells and excluded a myelodysplastic or hemophagocytic syndrome. After exclusion of an underlying EBV, CMV, HBV, HCV or HIV infection with negative serology and blood PCR the patient received one cycle of chemotherapy with cyclophosphamide, vincristine and prednisone. No improvement of renal function was achieved, while complication with a prolonged pulmonary infection and severe sepsis precluded further treatment. Our report indicates that the T-LGL leukemia should be considered in the differential diagnosis of renal failure with large-sized kidneys, especially when hepatosplenomegaly, pancytopenia and aseptic pyuria are also present. In the latter case, flow-cytometric and clonality analysis of the urine sediment can aid in establishing a diagnosis. Since renal function may deteriorate rapidly, chemotherapy should not be delayed.