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

Maxillary sinus metasasis from gastrointestinal stromal tumorGIST: A rarepresentation and literature review Yu-Ying Wu, Yi-Yang Chen, Kam-Fai Lee, Chun-Feng Wu, Ting-Yao Wang, Feng-Che K

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,

Feng-Che Kuan, Cih-En Huang, Ping-Tsung Feng-Chen, Chih-Feng-Cheng Feng-Chen, Kuan-Der Lee,

Chang-Hsien Lu

PII: S2311-3006(16)30154-9

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

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Case report

Maxillary sinus metasasis from gastrointestinal stromal tumor(GIST):

A rare presentation and literatures review

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*

1

Division of Hematology and Oncology, Department of Internal Medicine,

Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan

2

Department of Pathology, Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan 


3

Department of Medicine and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan

*Corresponding author: Chang-Hsien Lu M.D

*Tel:+886-5-3621000 ext.2853

Fax: +886-5-3623002

E-mail: q12014@cgmh.org.tw

Abstract

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

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Keywords : metastatic gastrointestinal stromal tumor, maxillary sinus

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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 [1,2,3] However, the incidence could in fact be higher in Asian 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 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, [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

successfully controlled by the treatment of tyrosine kinase inhibitor with Imatinib

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[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

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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

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 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 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 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 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

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regression of the right maxillary lesion (3.5 cm x 2 cm) She had better tolerance to the treatment with occasional nausea and poor appetite

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 (<1%)[8] In the pre-Imatinib era, the median survival duration of patients with recurrent or metastatic GIST was 10–20 months[9]; the median survival

increased to 51-57 months after the introduction of tyrosine kinase inhibitors [10, 11]

The most common site of metastasis both upon first diagnosis and relapse is the liver [12, 13] The other common sites of metastasis are the omentum, peritoneum, and other intra-abdominal sites.[12, 13] 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.[12, 13] 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 26-87 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

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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.[14] However, available data suggests that cytoreductive surgery may be considered for patients who show stable disease or limited radiographic progression

on Imatinib.[7] Besides, the use of Imatinib was suggested for patients with

metastatic GIST after metastasectomy for the benefit in overall survival.[6] 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 [8] Additionally, GIST with deletions in KIT exon 11 is also associated with frequent tumor recurrence than with a PDGFRA mutation [15] 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.[16] 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

In advanced GIST patients where a course of treatment of Imatinib is interrupted

by disease progression, subsequent rechallenge with Imatinib restored tumor control

in most patients In the prospective BFR14 trial, 25 patients with disease progression

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after interruption of one year of treatment restarted Imatinib 400 mg/day, and 20 patients (80%) achieved treatment response Among a group of 6 patients

interrupting Imatinib after 5 years of treatment that showed disease progression, 5 patients (88.3%) had response when rechallenging Imatinib [17] In the current case, the patient had disease progression after interruption of 3 years drug treatment, and later reintroduction of Imatinib showed efficacy in disease control

Conclusion

This report has presented a case of recurrent GIST with unusual oral cavity and maxillary sinus metastasis It also highlights the treatment efficacy of tyrosine kinase inhibitor rechallenge in an elderly patient, even with dosage reduction for

intolerance

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