Dramatic and durable efficacy of imatinib in an advanced angiosarcoma without detectable KIT and PDGFRA mutations

The tyrosine kinase (TK) inhibitor, imatinib, has revolutionized therapy of malignancies that are addicted to one of its target kinases, c-abl, c-kit and PDGF-R. This addiction is generally dependent on the acquisition of an activating kinase mutation, e.g., the bcr-abl fusion gene in chronic myeloid leukemia, or point mutations of KIT or PDGFRA in gastrointestinal stroma tumors (GIST). Other types of sarcomas are generally considered to be insensitive to imatinib. We have observed a striking and durable remission of an advanced angiosarcoma to imatinib that can only be explained by TK addiction. Unexpectedly, GIST-type KIT and PDGFRA mutations were absent in this case. This case illustrates the diagnostic challenges in identifying individual candidate patients for TK inhibitor therapy.