br Conclusions br Conflict of interest br Introduction
Conflict of interest
Introduction Gastrointestinal stromal tumor (GIST) arises from the mesenchymal tissue of the gastrointestinal tract. The annual incidence of this condition is 7 cases per million people in the West. However, the incidence could in fact be higher in Asian populations. The common sites of metastasis are the liver and abdominal viscera. The occurrence of extra-abdominal metastasis is rare in patients with GIST. The first-line systemic treatment of metastatic/unresectable GIST is Imatinib, but the treatment efficacy differs depending upon the genotype. In patients with KIT exon 11 mutant genotype, Imatinib demonstrates a higher response rate, longer time to disease progression and longer survival compared with GIST patients with mutation in KIT exon 9. Despite the fact that resection of metastasis from GIST would be beneficial in overall survival, radical surgery of all metastasis is not routinely recommended unless the disease is well-controlled by a tyrosine kinase inhibitor.
Case report An 87-year-old elderly woman presented to our facility with an oral cavity tumor over the right retromolar trigone area. She initially had right oral pain for one month, and an oral mass was found upon her visit to a local clinic. Thereafter, she was referred to this hospital. On physical and fiberscopic examination, we observed an irregular bulging tumor which protruded to the upper gum and ostiomeatal complex with bloody mucous (Fig. 1). Computed tomography of the head and neck showed a 7.2 cm × 5.2 cm soft tissue mass with faint heterogeneous enhancement over the right maxillary sinus, retromolar trigone and masticator space. The right maxillary sinus walls, internal and external pterygoid plate manifested bony destruction (Fig. 2). The patient\'s biopsy showed cores of mass composed of bizarre order SU 4312 with frequent mitoses. The pathology report by way of immunohistochemical staining of the tumor cells noted positive for vimentin and C-kit, and negative for AE1/AE3, S-100, P63 and desmin, which supported the diagnosis of metastatic GIST. The proliferation index was 20%, and the mitotic count was high grading with 5–10 mitoses per 50 high-power fields (Fig. 3). Nine years prior to the current oral cavity metastasis, the patient had been diagnosed with a jejunal tumor, which was completely removed with clear margins. One huge hepatic lesion was found a year later, after which she received hepatectomy at 79 years of age. Histological examination revealed a metastatic GIST. Target therapy was administered for her metastatic GIST using Imatinib (STI571, Glivec®/Gleevec®; Novartis Pharmaceuticals, Basle, Switzerland) at 200 mg daily, which was poorly tolerated by the patient. The treatment was interrupted and discontinued a few months later. Four years after the surgery, she received another hepatectomy at the age of 83 for recurrent liver metastasis. She had received Imatinib 300 mg daily for one year after surgery, then changed to 200 mg once a day for an additional 2 years due to grade 2 nausea and vomiting. Imatinib was discontinued at the age of 86 years due to grade 3 anemia. The diagnosis of distant metastasis of GIST to the maxillary sinus and retromolar trigone area was made. The c-kit exon mutational analysis showed deletion-insertion mutation in exon 11 of KIT and non-synonymous single-nucleotide polymorphism in exon 10 of PDGFRA. The choices of treatment included radiotherapy, surgical intervention, other targeted therapy or imatinib rechallenge. However, GIST had been considered radiation-resistant, and radiotherapy was recommended only for palliation of bone metastases in the current treatment guidelines. Given the extensive field potentially involved, radical surgery was not suggested for this frail elderly woman with such a tumor location. Additionally, the possibility of adverse events with higher dosage imatinib or switching to sunitinib are major concerns for this frail elderly patient. Because the patient\'s disease had been well-controlled in previous imatinib rounds with reduced dosage, the patient received Imatinib 400 mg once a day. The follow-up CT after Imatinib treatment for one year showed regressive change of the right oral mass (4.2 cm × 2.2 cm) with sinus and bony invasions (Fig. 2). Due to intolerance with nausea and vomiting, the dosage of Imatinib was changed to 300 mg daily. The most recent follow-up image in May 2016 showed continuing regression of the right maxillary lesion (3.5 cm × 2 cm). She had better tolerance to the treatment with occasional nausea and poor appetite.