An 82-year-old man presented with leukocytosis and splenomegaly. His blood counts showed a white cell count of 134 × 109/l, hemoglobin 96 g/l, and platelet count 86 × 109/l. The blood film showed two distinct populations of lymphocytes, morphologically, 60% typical CLL cells and 40% large prolymphocytes (Image 1). Patient's spleen was palpable 14 cm below the left costal margin. There were mildly enlarged cervical and axillary lymph nodes up to 2 cm but no evidence of localized lymphoma.

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Figure 1. Blood film shows two populations of CLL and PLL cells.

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Flow cytometry analysis showed 90% B lymphocytes. Although all the B cells had lambda light chain restriction, they were heterogeneous for CD5 and CD23 expression, including the CD5+/CD23+ B cells typical of CLL phenotype, and the cells lacking CD5 and CD23 consistent with a PLL population. Clonality analysis was performed with use of multiplex PCR (polymerase chain reaction) assays for IgH rearrangement. With this assay, a clonal B-cell population gives rise to PCR product identical in size and independent clones can be distinguished by unique size of the PCR products. The patient's blood sample showed a pattern of two clones of B lymphocytes (Image 2), indicating the two independent clones of CLL and PLL cells.

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Figure 2. PCR clonality analysis is based on IgH gene rearrangement and two peaks of PCR products indicate two independent clones of B cells.

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The patient was treated initially with chlorambucil 2 mg daily with a poor response. His white cell count rose quickly to 240 × 109/l in 5 months. He required transfusion for worsening anemia. Further treatment with fludarabine and cyclophosphamide was tried and discontinued due to poor intolerance.

This patient presented with a mixed population of CLL and PLL. The genetic relationship between CLL and PLL may be revealed by immunoglobulin isotypes or immunoglobulin gene rearrangements [1]. Similar to diffuse large B-cell lymphoma developing in CLL (Richter syndrome), B-cell PLL may arise from clonal progression of CLL or a second malignancy unrelated to CLL [1–3]. It is likely that this patient had an indolent and undiagnosed CLL, but the duration of CLL before the emerging PLL is unclear. Nonetheless, the finding of clonality analysis indicates PLL derived from an independent clone to that of CLL.


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