title: Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma.
abstract: We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.
authors.affiliation: Academic Department of Haematology and Cytogenetics, Royal Marsden Hospital, NHS Trust, Fulham Road, London SW3 6JJ, UK. estella@icr.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: A C
authors.initials: AC
authors.lastname: Wotherspoon
authors.forename: N E
authors.initials: NE
authors.lastname: Parker
authors.forename: N
authors.initials: N
authors.lastname: Osuji
authors.forename: P G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D015458:Leukemia, T-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D017254:Leukemic Infiltration; D008198:Lymph Nodes / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D016827:CD8 Antigens