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Dasatinib-related Follicular Hyperplasia: An Underrecognized Entity With Characteristic Morphology
Michael G Ozawa1, Mark D Ewalt, Dita Gratzinger
1Department of Pathology, Stanford University School of Medicine, Stanford, CA.
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.
Insights
Dasatinib therapy for chronic myelogenous leukemia can cause lymphadenopathy. This condition mimics other diseases, requiring careful diagnosis to avoid unnecessary procedures.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Dasatinib is a tyrosine kinase inhibitor used for chronic myelogenous leukemia (CML).
- Lymphadenopathy has been observed in CML patients on long-term dasatinib treatment.
- The full morphologic and immunophenotypic features of this adverse effect require detailed description.
Observation:
- Three cases of unexplained lymphadenopathy in CML patients receiving long-term dasatinib therapy are presented.
- Morphologic analysis revealed preserved nodal architecture with features of progressive transformation of germinal centers and Castleman-type changes.
- Abnormalities included disrupted germinal centers, IgD+ mantle zone infolding, decreased CD20 expression, and increased Epstein-Barr virus reactivity.
Findings:
- The observed lymphadenopathy exhibits hybrid morphologic features, distinct from typical reactive changes.
- Immunophenotypic analysis showed decreased CD20 expression and variable Epstein-Barr virus reactivity.
- B-cell clonality studies did not reveal predominant clonal rearrangements, suggesting a non-neoplastic process.
Implications:
- Recognizing dasatinib-related lymphadenopathy is crucial for accurate diagnosis in CML patients.
- This recognition can prevent unnecessary diagnostic procedures and associated patient burden.
- Understanding this adverse effect aids in managing CML patients on dasatinib therapy.
