maxillary sinus metastasis from gastrointestinal stromal tumor gist a rare presentation and literature review

Accepted Manuscript Maxillary sinus metasasis from gastrointestinal stromal tumor(GIST): A rare presentation and literature review Yu-Ying Wu, Yi-Yang Chen, Kam-Fai Lee, Chun-Feng Wu, Ting-Yao Wang, FengChe Kuan, Cih-En Huang, Ping-Tsung Chen, Chih-Cheng Chen, Kuan-Der Lee, Chang-Hsien Lu PII: S2311-3006(16)30154-9 DOI: 10.1016/j.jcrpr.2016.11.004 Reference: JCRPR 45 To appear in: Journal of Cancer Research and Practice Received Date: 29 July 2016 Revised Date: 13 November 2016 Accepted Date: 21 November 2016 Please cite this article as: Wu YY, Chen YY, Lee KF, Wu CF, Wang TY, Kuan FC, Huang CE, Chen PT, Chen CC, Lee KD, Lu CH, Maxillary sinus metasasis from gastrointestinal stromal tumor(GIST): A rare presentation and literature review, Journal of Cancer Research and Practice (2017), doi: 10.1016/ j.jcrpr.2016.11.004 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT Case report Maxillary sinus metasasis from gastrointestinal stromal tumor(GIST): A rare presentation and literatures review RI PT Yu-Ying Wu1, Yi-Yang Chen1, Kam-Fai Lee2, Chun-Feng Wu1, Ting-Yao Wang1, Feng-Che Kuan1, Cih-En Huang1, Ping-Tsung Chen1,3, Chih-Cheng Chen1,3, Kuan-Der Lee1,3, Chang-Hsien Lu1,3* Division of Hematology and Oncology, Department of Internal Medicine, SC Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan Department of Pathology, Chang Gung Memorial Hospital-Chiayi, Chiayi, M AN U Taiwan
 Department of Medicine and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan *Corresponding author: Chang-Hsien Lu M.D TE D *Tel:+886-5-3621000 ext.2853 Fax: +886-5-3623002 Abstract EP E-mail: q12014@cgmh.org.tw AC C Gastrointestinal stromal tumor (GIST) arises from the mesenchymal tissue of the gastrointestinal tract It develops in the abdominal cavity and mostly the metastasis is limited to the liver and abdominal viscera Metastasis beyond extra-abdominal site is rare in patients with GIST Metastatic GIST to maxillary sinus is an extremely rare presentation and diagnostic challenge to clinicians The treatment of metastatic GIST differs from squamous cell carcinoma of head and neck and tyrosine kinase inhibitor is the mainstay of therapy We herein reported a case of 87-year-old lady diagnosed with recurrent GIST with metastasis to maxillary sinus and successfully treated with target therapy ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT Keywords : metastatic gastrointestinal stromal tumor, maxillary sinus ACCEPTED MANUSCRIPT Introduction Gastrointestinal stromal tumor (GIST) arises from the mesenchymal tissue of the gastrointestinal tract The annual incidence of this condition is cases per million people in the West [1,2,3] However, the incidence could in fact be higher in Asian RI PT populations [4,5] 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 SC 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 Despite the fact that resection of metastasis from GIST would be M AN U beneficial in overall survival, [6] radical surgery of all metastasis is not routinely recommended unless the disease is well-controlled by a tyrosine kinase inhibitor [7] Herein we report a case of recurrent GIST with KIT exon 11 mutation presenting with a rare metastasis to the oral cavity and maxillary sinus The tumor was Case report TE D successfully controlled by the treatment of tyrosine kinase inhibitor with Imatinib An 87-year-old elderly woman presented to our facility with an oral cavity tumor EP 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 AC C 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[Figure 1] Computed tomography of the head and neck showed a 7.2 cm x 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 [Figure 2] The patient’s biopsy showed cores of mass composed of bizarre cells 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 ACCEPTED MANUSCRIPT The proliferation index was 20%, and the mitotic count was high grading with 5~10 mitoses per 50 high-power fields [Figure 3] Nine years prior to the current oral cavity metastasis, the patient had been RI PT 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, SC Glivec®/Gleevec®; Novartis Pharmaceuticals, Basle, Switzerland) at 200mg 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 M AN U hepatectomy at the age of 83 for recurrent liver metastasis She had received Imatinib 300mg daily for one year after surgery, then changed to 200mg once a day for an additional years due to grade nausea and vomiting Imatinib was discontinued at the age of 86 years due to grade anemia The diagnosis of distant metastasis of GIST to the maxillary sinus and retromolar TE D 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 EP been considered radiation-resistant, and radiotherapy was recommended only for palliation of bone metastases in the current treatment guidelines Given the AC C 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 x 2.2 cm) with sinus and bony invasions [Figure 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 ACCEPTED MANUSCRIPT regression of the right maxillary lesion (3.5 cm x cm) She had better tolerance to the treatment with occasional nausea and poor appetite RI PT Review & Discussion GISTs originate from the interstitial cells of Cajal They occur commonly in the stomach (50–60%), the small intestine (30–35%), the colon and rectum (5%) and the esophagus (