Gynecomastia is defined as enlargement of the glandular tissue in male breasts. Gynecomastia is an uncommon manifestation during treatment with a tyrosine kinase inhibitor, such as dasatinib or imatinib, with only a few reports of this occurrence. We describe a case highlighting this event and propose a potential treatment.

A 38-year old African American Male with a PMH of asthma was seen in the ER with symptoms of abdominal pain and diarrhea for three days as well as early satiety and weight loss. His complete blood count was significant for a white blood count of 422,000/mm3 with neutrophil predominance but also with the presence of metamyelocytes, myelocytes, basophils, and few blasts. CT scan of the abdomen/pelvis revealed splenic enlargement of 18 cm in greatest dimension. Bone marrow cytogenetics showed a reciprocal translocation of the long arm of chromosome 9 and the long arm of chromosome 22 and PCR was positive for BCR/ABL gene fusions indicative of Chronic Myeloid Leukemia. He was initially started on hydroxyurea which was subsequently replaced by dasatinib as an outpatient. Two months after starting dasatinib, patient developed tender gynecomastia. Dasatinib was discontinued and patient was subsequently started on imatinib and on follow-up gynecomastia completely resolved.

Dasatinib is a potent inhibitor of Src kinase and reports have shown these proteins to be important in transducing the signal for testosterones action on sertoli cells. Receptor tyrosine kinases, c-Kit and PDGFR-α are expressed in the testis and believed to be part of the biosynthetic process of testosterone. Imatinib inhibits c-Kit and PDGFR-α, also decreasing testosterone production. In contrast to Imatinib, second generation TKIs, such as dasatinib, have multiple targets and are known to cause a more potent inhibitory action on c-Kit and PDGFR-α. A comparison of hormone concentrations of these patients showed that the patients who developed gynecomastia had a reduction in free testosterone concentrations. As Imatinib has been used for a longer time in management of CML, more cases of gynecomastia have been reported. Despite this, our case demonstrates that imatinib can be used in management of CML patients who develop this complication with other TKIs.

References and Resources:

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