Polyclonal B-cell lymphocytosis: a rare, benign condition that mimics a chronic lymphoproliferative disorder

We report a case of Persistent polyclonal B-cell lymphocytosis (PPBL), a rare and benign lymphoproliferative disorder, to highlight the importance of recognising its characteristic features in order to avoid unnecessary investigations and inappropriate treatment. We also underscore the potential reversibility of disease features with smoking cessation.

The patient presented with a prolonged history of low-level abdominal discomfort and unintentional weight loss on a background of a significant smoking history. Physical examination revealed splenomegaly. The laboratory results revealed a persistent lymphocytosis, prompting a referral to a haematology specialist with a working diagnosis of a malignant lymphoproliferative disorder. Subsequent investigations revealed markedly elevated polyclonal IgM with no monoclonal paraprotein via serum electrophoresis. A peripheral blood smear demonstrated characteristic binucleate lymphocytes, and flow cytometry confirmed polyclonal B-cell expansion with a normal immunophenotype. Molecular and cytogenetic analysis excluded B-cell neoplasia and supported a final diagnosis of PPBL.

PPBL can closely mimic malignant chronic lymphoproliferative disorders. Recognition of its characteristic laboratory and morphological features, namely polyclonal lymphocytosis, atypical binucleated lymphocytes, and elevated serum immunoglobulin M (IgM) without a monoclonal paraprotein, is essential to avoid unnecessary invasive investigations and inappropriate treatment. PPBL pathogenesis remains elusive but is likely to involve a genetic predisposition and chronic antigen stimulation. Cigarette smoking appears to be the dominant environmental trigger, with cessation often leading to stabilisation or resolution of lymphocytosis. The role of the Epstein‒Barr virus has been proposed given the binucleated lymphocytes and polyclonal B-cell expansion, but evidence remains inconclusive.

This case highlights the importance of recognising PPBL to avoid unnecessary invasive investigations and inappropriate treatment and underscores the potential reversibility of disease features with smoking cessation.