Lymphocytosis, lymphadenopathy: benign or malignant?

The increasing use of immunophenotypic and molecular analysis in the routine evaluation of patients with lymphocytosis, lymphadenopathy, or other hematologic disorders has led to the identification of unexpected small clonal lymphoid populations. These clones, sometimes with disease-specific markers, such as the t(14;18), are especially challenging for the clinician because of their unknown biologic potential and uncertain clinical behavior. Study of these early lymphoid lesions is providing important clues to the process of lymphomagenesis, and may provide the rationale for preemptive therapy in the future. More and more, the hematologist/oncologist is consulted regarding otherwise healthy individuals with lymphadenopathy and/or lymphocytosis, and pathology reports that confound the referring internist or surgeon. The report does not name a malignant lymphoproliferative disorder, but is not completely "normal". Does the patient have a benign or malignant condition? How should they be evaluated? Is treatment indicated? These patients prove challenging for the consulting hematologist as well as the referring physician. In this review, we will focus on some of these scenarios and attempt to provide guidance for their management.