Review of the literature Outside of a retrospective analysis conducted by Schuler et al (5), which reported that seventeen

out of 307 patients with GIST had bone metastases, there are only a few reported cases in the literature of patients with GIST metastases to the bone, lung, or both (Table 1). Kaku et al (8) described a case of a 68 year-old woman with intracranial metastasis occurring two years after surgical resection of a GIST tumor of the sacrum. She subsequently developed metastatic tumor involving the lumbar spine and ureter. The intracranial metastasis was resected by right parietal craniotomy and was c-KIT Inhibitors,research,lifescience,medical positive by immunohistochemistry. Biopsy or surgery was not performed on the lumbar spine and ureter lesions. A Inhibitors,research,lifescience,medical 37 year-old man with primary GIST of the liver metastatic to the lung is described by DeChiara et al (9). The primary tumor was initially diagnosed as a high grade sarcoma, but after further immunohistochemical study, the liver tumor cells stained positively for c-KIT and the tumor was diagnosed as GIST. Fourteen Inhibitors,research,lifescience,medical months after this diagnosis, the patient was found to have lung metastases by CT scan, and confirmed by PET. While pathology and immunohistochemistry were not reported on the lung metastases,

it was reported that the pulmonary lesions disappeared completely with oral imatinib treatment, suggesting a similar molecular basis of these lesions. Miyake et al Inhibitors,research,lifescience,medical (10), and Inage et al (11), described patients with multiple sites of metastases, with both patients having lung metastases. Ishikawa et al (12) reported a patient with liver and bone metastases, in the form of a lumbar vertebral lesion. With the exception of our report, mutational studies of KIT and Inhibitors,research,lifescience,medical PDGFRA genes were not reported in these five other cases (8)-(12). Table 1. Case Reports describing GIST metastasis to bone, lung, or both. Even more rare than metastases to bone and lung, metastases of GIST to subcutaneous Vorinostat datasheet tissue are

reported in less than 1% of cases (6),(7). In a series of patients with stomach GIST, five out of 1765 patients (0.04%) developed skin or soft tissue metastases (6). No patients were reported to have soft tissue or skin metastases in a series of 906 patients with small intestine GIST (7). Prior to our reported case, the literature includes six case reports (13)-(18) Megestrol Acetate describing ten patients with cutaneous metastases as a late complication of GIST. The first reported case (13) described a 49 year-old male with multiple skin and subcutaneous metastases to the scalp, anterior jaw, left thigh, and groin, along with liver and splenic metastases. This report did not include description of microscopic, immunohistochemical and molecular features. The patient was treated with gemcitabine and thalidomide, experienced a minimal response and was then lost to follow up.