Reactive follicular hyperplasia during dasatinib treatment: an underestimated adverse event

Dasatinib (DAS) shows a distinct toxicity profile among which a previously unrecognized adverse event (AE) is represented by persistent lymphadenopathy with reactive follicular hyperplasia (FLH). The latter is a common cause of lymphadenopathy and encompasses a constellation of morphologic and immunophenotypic features. Recently, lymphadenopathy with morphologic features of reactive FLH has been described in two small series of long-term DAS-treated CML patients. However, only in a few patients complete morphologic and immunophenotypic features of this AE was reported. Herein, we describe 2 cases of patients with chronic phase (CP)-CML who presented with unexplained lymphadenopathy after front-line therapy with DAS. Case 1: in October 2012 a 30-year-old man was diagnosed with CP-CML and he was treated with DAS front-line, rapidly obtaining a major and subsequently a deep molecular response. DAS was well tolerated but approximately after 48 months he acceded to our Hospital because of the appearance of bilateral cervical lymphadenopathy. Case 2: in April 2016 a 49-year-old man was diagnosed with CP-CML and he was treated with DAS front-line. The drug was well tolerated and after 12 months of therapy he obtained a major molecular response. Nevertheless, he acceded to our Hospital because of the appearance of a swelling at the angle of the left mandible and concomitant bilateral cervical, preauricular and sovraclavear lymphadenopathy. For both patients no generalized lymphadenopathy was noted and no constitutional symptoms were reported. As screening for active viral infection was negative and no signs of local or systemic infectious disease were detected, an excisional biopsy was performed, showing in both cases enlarged lymph nodes with overall preserved architecture, follicular and paracortical hyperplasia with a reactive phenotype (BCL2-/BCL6+/CD10+), a predominance of small CD3+, CD5+ T-lymphocytes mixed with much rarer enlarged CD45+, CD30-/+, CD15-, CD20+/- lymphocytes with blastic morphology. In situ hybridization for EBV-encoded RNA was negative. A diagnosis of FLH was made, ruling out an extramedullary blastic transformation of CML. Then, both patients definitely discontinued DAS, achieving clinical resolution of lymphadenopathy. Therefore, we support the importance of a careful clinical examination of lymph nodes in all DAS-treated CML patients and provide additional information concerning the real incidence and the correct management of this AE.