[Classification and pathogenesis of malignant lymphomas]

The classification of malignant lymphomas according to the WHO scheme of 2001 is based on modern knowledge of B- and T-cell differentiation, the immunophenotype and genetic alterations of the neoplastic cells, as well as on clinical features. Conventional histology does not suffice for a reliable diagnosis of lymphoma diseases and the application of additional methods is required. Immunophenotyping by means of immunohistochemistry is indicated in practically all instances. In a number of cases, the analysis of clonality by PCR and cytogenetic alterations by FISH also need to be applied. A high risk cause of B-cell lymphomagenesis involves rearrangements at the immunoglobulin locus and events occurring during the germinal centre reaction (somatic mutations and immunoglobulin heavy chain class switch) which may result in molecular accidents in the form of chromosomal translocations and/or gain or loss of functional mutations. This may disrupt B-cell homeostasis resulting in increased proliferation, inhibition of apoptosis or both. Clinical behaviour may be influenced by the microenvironment, e.g. T-cells, cytokines and pathogenic microorganisms.