Response to imatinib mesylate (IM) in fibrosarcoma (FS) arising in dermatofibrosarcoma protuberans (DFSP).

10593 Background: IM is active in DFSP by targeting PDGFRB that is constitutively activated in this rare low grade malignant tumor as a consequence of the chromosomal translocation t (17;22). Fibrosarcomatous transformation rarely occur in DFSP, with an increased risk for metastasis. IM activity in FS arising from DFSP is less well defined.,From June 2007, 2 patients with metastatic high- grade FS in DFSP (both men, age 45/75, PS 2) were treated with IM 400 mg/day. Both cases have been investigated by FISH analysis for t (17;22) in the DFSP and in the FS component. We also review all patients (pts) surgically treated at our institution from 1997 for localized FS in DFSP.,Both pts treated with IM had a RECIST PR, along with PET and subjective major response after 4 weeks of treatment (SUV max decrease >75%), but they both dramatically progressed, after 4 months in one case (A) and after 5 months in the second (B). Pt A underwent macroscopically complete surgery of a mediastinic metastatic lesion after progression, with no evidence of response on the surgical specimen. Pt B died 1 month later for brain metastasis. By FISH analysis the fusion gene was present before treatment with IM in both tumor components, in the same proportion (2-3 fusion gene/nucleus). Biochemical and cytogenetic analyses on patient A metastasis are ongoing. A retrospective analysis was made in 205 pts surgically treated at our institution for localized DFSP: 12 showed a fibrosarcomatous component. Only 2 pts of this series relapsed with distant metastases, to the brain in one case. Both pts died in a few months. Pathology of these 12 patients is under review and FISH analysis is ongoing.,FS in DFSP can maintain the t (17;22) translocation and can be sensitive to IM, but the response may be short in time. Of interest, CNS metastases have been observed in this series. The molecular basis of disease progression on IM is under study. [Table: see text].