Leptomeningeal dissemination of chronic lymphatic leukemia (CLL). Molecular analysis of cerebrospinal fluid (CSF)

The diagnosis of leptomeningeal dissemination of chronic lymphatic leukemia (CLL) by conventional cytology is unreliable because cytomorphologic crite ria of malignancy are often lacking. Immunophenotyping of leukocyte differe ntiation antigens may also be of limited diagnostic value due to the small number of cells in cerebrospinal fluid (CSF) samples. Molecular methods may support the specific diagnosis of leptomeningeal infiltration of CLL. We p resent an 54 old patient who was diagnosed with CLL five years ago. Despite clinical signs of leptomeningeal involvement neither magnetic resonance im aging (MRI) nor conventional CSF analysis were suggestive of lymphomatous m eningitis. Using PCR we selectively amplified the highly variable and clone -specific CDR3 region of the locus encoding the immunoglobulin heavy chain (IgH) in DNA obtained from both CSF and peripheral brood cells. Analysis of PCR products by high resolution gel electrophoresis revealed a single DNA fragment respectively indicating the presence of a monoclonal cell populati on in both compartments. DNA sequence analysis of the amplified CDR3 segmen ts confirmed the clonal identity of cells and the leptomeningeal disseminat ion of CLL.