title: Dasatinib-related Follicular Hyperplasia: An Underrecognized Entity With Characteristic Morphology.
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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ozawa
authors.forename: Mark D
authors.initials: MD
authors.lastname: Ewalt
authors.forename: Dita
authors.initials: D
authors.lastname: Gratzinger
mesh_terms: D018951:Antigens, CD20 / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001706:Biopsy; D000069439:Dasatinib / Q000009:adverse effects*; D057915:Drug Substitution; D005434:Flow Cytometry; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008206:Lymphatic Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*
chemical_list: D018951:Antigens, CD20; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069439:Dasatinib