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The differential diagnosis of absolute lymphocytosis is variegated. In general, reactive (secondary) lymphocytosis can be well differentiated from a lymphoproliferative disease (primary lymphocytosis). Together with correspondent clinical characteristics, an absolute lymphocytosis often suggests a potential diagnosis and the further diagnostic process. Reactive lymphocytosis is usually self limiting and normalizes after cessation of the inflammatory stimulus. If a lymphoproliferative disorder is suspected further diagnostic procedures (i.e. cytometry, bone marrow examinations, biopsies of other organs if needed and molecular analyses) should be performed. If the distinction between malignant lymphoproliferation and reactive lymphocytosis cannot be done immediately, a watch and wait strategy may be implemented. In case of persistent lymphocytosis for longer than six months or occurrence of additional symptoms earlier on, diagnosis should be forced.