br Discussion GISTs originate from the interstitial
Discussion GISTs originate from the interstitial abnormal lipid metabolism of Cajal. They occur commonly in the stomach (50–60%), the small intestine (30–35%), the colon and rectum (5%) and the esophagus (<1%). In the pre-Imatinib era, the median survival duration of patients with recurrent or metastatic GIST was 10–20 months; the median survival increased to 51–57 months after the introduction of tyrosine kinase inhibitors. The most common site of metastasis both upon first diagnosis and relapse is the liver. The other common sites of metastasis are the omentum, peritoneum, and other intra-abdominal sites. In two large study series, only eight percent (8%) of patients developed extra-abdominal metastasis. In general, bone and lung are the leading two extra-abdominal metastasis sites. Metastasis of GIST to the head and neck region is extremely rare, in that only 6 cases have been reported in the literature to date. We herein have reported the 7th case for its rarity and unusual clinical presentation. These 7 case reports of metastatic GIST to the head and neck region are summarized in Table 1. The age of these patients ranged from 26 to 87 years (mean, 60.7 years). The tumors originated from the stomach, small bowel, rectum and mesentery. All these patients had bony metastasis, four with synchronous liver metastasis and one with lung metastasis. The treatment strategy was different: four cases received Imatinib alone, one case received tumor excision followed by Imatinib (case 4), one case received radiation (case 5), and one case received surgery, radiation and Nilotinib (case 6). The outcomes were different and have been summarized in Table 1. Among these 7 cases, 5 were treated with Imatinib. Mutation in exon 11 was found in 2 patients, and treatment with Imatinib was effective. Our case was the oldest reported case and had good response to Imatinib with dosage reduction for side effect and intolerance. We found two cases (case 3 and case 5) where the patients died within a year after treatment. They received either radiation alone or Imatinib alone. On the other hand, case 4 received excisional surgery following by Imatinib, where no further metastasis was reported. It would appear that cytoreductive surgery or metastasectomy may have a role in the treatment of metastatic GISTs. According to some randomized controlled trials, cytoreduction prior to initiation of Imatinib offers no benefit. However, available data suggests that cytoreductive surgery may be considered for patients who show stable disease or limited radiographic progression on Imatinib. Besides, the use of Imatinib was suggested for patients with metastatic GIST after metastasectomy for the benefit in overall survival. In this current case, the patient had repeated hepatectomy for metachronous liver metastasis. Adjuvant Imatinib with dose reduction had been used for 3 years after the second metastasectomy, but another metastasis occurred one year after drug discontinuation. The adjuvant Imatinib, even on reduced dose and schedule interruption, still showed efficacy in metastatic GIST after metastesectomy. GISTs arise from the small intestine, and have a greater risk of recurrence than when arising from the stomach. Additionally, GIST with deletions in KIT exon 11 is also associated with frequent tumor recurrence than with a PDGFRA mutation. Late recurrence of metastatic GIST is defined as five years after excision of localized disease. In a retrospective study of recurrent GIST, there were 6 patients with late recurrence from a total of 42 recurrent GIST cases. These late recurrent cases of metastasis were mostly located in the liver, and not the head and neck region. Interestingly, 4 cases had primary site in the small intestine, and 3 cases had c-KIT exon 11 mutation in their tumors. In this current case, the primary site of GIST was located in the jejunum and harboring a KIT exon 11 mutation. She had frequent metastasis and a clinical course of nine years from initial diagnosis to present maxillary sinus metastasis. This presentation was in line with previous findings.