Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms, and metastatic disease is present at diagnosis in about 50%. Most common metastatic sites are the liver, the lungs, and the peritoneum. Bony metastases are uncommon and of unknown prognosis. Case Report: A 57-year-old man presented with diplopia due to a clival metastastic lesion from an asymptomatic rectal stromal tumor. This patient also had liver and vertebral metastases. Treatment with imatinib, a tyrosine kinase inhibitor, led to a partial response of the primary tumor and hepatic metastasis, but the patient developed aggressive bone metastases that proved refractory to 3 different tyrosine kinase inhibitors. Con-clusion: Different drug distribution or different mutation patterns of key prognostic receptors (e.g. cKIT receptor) in bone and soft tissues may explain the unusually aggressive pattern of these bony metastases of a GIST. Pharmacodynamic and molecular investigations are warranted to check these hypotheses.

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