Ribosome-lamella complexes in a patient with aggressive chronic lymphocytic leukemia

Ribosome-lamella complexes (RLCs) are rarely found intracytoplasmic organelles intimately associated with the rough endoplasmic reticulum (RER). RLCs have been observed in different conditions but most often in hematological malignancies, and especially in hairy cell leukemia [1 – 3]. Although RLCs were first described in a patient with chronic lymphatic leukemia (CLL) [4], this association was infrequently reported subsequently. Recently the presence of these structures was reported in a case of aggressive NK cell leukemia [5]. We report on a patient with CLL with an aggressive course, characterized by splenomegaly, enlarged lymph nodes, autoimmune hemolytic anemia (AIHA), and increased number of lymphocytes with an unusual morphology. Ultrastructural studies of the leukemic cells revealed RLCs in an unusually high number. A 68-year-old woman was diagnosed with CLL in 1996. At diagnosis leukemic B cells expressed CD5 and CD19 antigens in a proportion of 60 and 40%, respectively. The clinical stage was evaluated as Rai 0. Chromosomal and ultrastructural analyses were not performed at that time. After an uneventful follow-up without therapy for 5 years, the patient presented with tiredness and generalized lymphadenopathy. Physical examination revealed jaundice, enlarged lymph nodes on the neck, axillar and inguinal regions and an enlarged spleen of 6 cm below the costal margin. Blood tests showed hemoglobin 7 g/dl, white blood cell count 706 10/l with 70% lymphocytes, platelets 1506 10/l. The peripheral blood (PB) smear revealed a large number of lymphocytes and smudge cells, a third of the lymphocytes were of medium size and showed indented and/or convoluted nucleus with one or two nucleolei and a basophilic cytoplasm [Figure 1A]. On flow cytometry analysis the cells showed strong dual expression of CD5 and CD19 antigens (90%) and also expression of CD23 (60%) and CD38 (35%) antigens, while the expression of FMC 7 antigen was only 4% and the surface immunoglobulin staining was negative. Other laboratory tests showed: reticulocytes 10%, total bilirubin 2 mg/dl (normal 0.1 – 1 mg/dl), indirect bilirubin 1.2 mg/dl (upto 0.8), LDH 748 u/l (230 – 460 u/l), haptoglobin 5 mg/dl (above 35 mg/dl), total protein 6 g/dl, IgG 551 mg/dl, IgM 168 mg/dl, IgA 68 mg/dl, b-2microglobulin 2918 mg/l (up to 1990). The Coombs test was positive with IgG and C3d antisera. Immunoelectrophoresis and immunofixation revealed a small monoclonal spike of IgM kappa type. Bone marrow (BM) aspiration disclosed diffuse infiltrate of small and medium sized lymphocytes and increased number of prolymphocytes with morphology similar to those described the PB; marked erythroid hyperplasia was also noticed. A touch preparation of a peripheral lymph node aspiration revealed the same type of lymphatic cells present in the PB and BM. Electron microscopic examination of the PB leukemic lymphocytes revealed single or multiple RLCs in 20% of the cells. These organelles were observed in both transverse and longitudinal sections [Figures 1B – E]. Chromosome 13q and 11q deletions were identified by fluorescent in situ hybridization. Treatment with chlorambucil, prednisone, and folic acid was started. The hemolytic process stopped