Diagnostic issues in chronic lymphocytic leukaemia (CLL)

The diagnosis of chronic lymphocytic leukaemia (CLL) is based on clinical and laboratory features. Morphology and immunophenotype are the initial diagnostic investigations. In atypical cases, these tests should be complemented with molecular genetics and/or histology to exclude other B-cell disorders of small lymphocytes. Morphologically, CLL can be classified into typical and atypical. Immunophenotyping is the only method that can establish or confirm the diagnosis as CLL lymphocytes have a distinct immunophenotypic signature. A scoring system compounding the results with a set of markers allows firming up the diagnosis. Other immunological markers such as CD38 and ZAP-70 have an important prognostic impact. Fluorescence in situ hybridization (FISH) analysis, chiefly by detecting 17p (TP53 locus) and 11q (ATM) deletions and mutational status of the IgVH gene, also provides prognostic information and may determine the type of therapy. In atypical CLL, histology and/or molecular genetics may be required to exclude other B-cell disorders.