Dasatinib-related Follicular Hyperplasia: An Underrecognized Entity With Characteristic Morphology. (October 2015)

• Record Type: Journal Article
• Authors: Ozawa, Michael G.; Ewalt, Mark D.; Gratzinger, Dita
• Is Part Of: American journal of surgical pathology. Volume 39:Number 10(2015)
• Publication Date: 2015-10
• Subjects: Castleman disease -- chronic myelogenous leukemia -- EBV -- dasatinib -- progressive transformation of germinal centers; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000488
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Dasatinib, a second-generation tyrosine kinase inhibitor with activity against BCR-ABL1 and other Src family tyrosine kinases, is approved as a first-line treatment option for Philadelphia chromosome–positive chronic myelogenous leukemia (CML) in the chronic phase. Recently, lymphadenopathy with morphologic features of reactive follicular hyperplasia was described in a cohort of patients with CML on long-term dasatinib therapy. However, the complete morphologic and immunophenotypic features of this previously underappreciated adverse effect have not been fully described. Herein, we report 3 cases of unexplained lymphadenopathy resulting in multiple diagnostic procedures in patients with CML and a history of long-term dasatinib therapy. Morphologic examination demonstrated preserved nodal architecture showing hybrid features of progressive transformation of germinal centers and Castleman-type changes in a background of florid follicular hyperplasia. Large germinal centers were disrupted by complex infolding of IgD + mantle zones arranged as cuffs surrounding perforating capillaries. Other abnormalities variably present included decreased CD20 expression among polytypic B cells and increased Epstein-Barr virus reactivity in scattered paracortical cells and/or individual germinal centers. B-cell clonality studies showed no predominant clonal rearrangements. Consideration of dasatinib-related lymphadenopathy may pre-empt unnecessary repeat diagnostic procedures in patients with CML or other dasatinib-susceptible malignancies and persistent lymphadenopathy.