Oesophageal GIST
- 1 Hospital Sao Francisco Xavier, Lisboa, Portugal
- 2 Instituto Portugues de Oncologia de Lisboa Francisco Gentil EPE, Lisboa, Portugal
- Correspondence to Dr Filipa Costa; filipacc@gmail.com
Abstract
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. Oesophageal GISTs are extremely uncommon, accounting for 0.7% of all GISTs, and their management is surrounded by some debate. We report a case of a 70-year-old man who was incidentally diagnosed with an oesophageal lesion on a 18F-fluorodeoxyglucose positron emission tomography. An endoscopic study revealed a non-obstructing 40 mm oesophageal lesion. Endoscopic ultrasound showed a well-circumscribed submucosal tumour on the middle oesophagus. Fine-needle aspiration was positive for CD117 and the overall features were of a GIST. After an initial thoracoscopic approach, the tumour was completely enucleated through a thoracotomy incision. The patient experienced no surgical complications and was discharged on day 4. Histopathology and immunohistochemical staining confirmed a low-risk GIST.
Background
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the gastrointestinal tract, arising from interstitial pacemaker cells of Cajal present in the myoenteric plexus. They represent 1%–2% of all gastrointestinal malignancies. For the most part, they occur in the stomach (60%–70%) and small intestine (20%–30%). Oesophageal GISTs are extremely uncommon, accounting for 0.7% of all GISTs.
A major obstacle to the comprehensive understanding of oesophageal GISTs and their appropriate management is the rarity of this disease that results in limited data on the subject.1–9
The clinical presentation of oesophageal GIST varies according to the location and size of the tumour. The symptoms are often unspecific. Dysphagia (57%), obstruction (10%–30%), gastrointestinal bleeding (about 50%) and abdominal pain (20%–50%) are most common.1–3
Twenty per cent of tumours are incidental findings at endoscopy, radiological imaging or surgery for other reasons.3
GISTS can be confused with leiomyomas, leiomyoblastomas and leiomyosarcomas. Immunohistochemical staining for CD117 and CD34 were traditionally used to distinguish them from these other tumours. However, although CD34 was widely used, it is no longer used because it is not specific for GIST. Nowadays, CD117 and DOG-1 are the most sensitive and specific markers, and immunohistochemical diagnosis relies on their positivity.1 2 7
There is still some debate around the negative consequences of a preoperative biopsy. However, its use is increasingly more common because it is important to have an accurate preoperative diagnosis and there are no proven side effects of its use.
Even in the era of imatinib, a tyrosine kinase inhibitor and in the absence of metastatic disease, the most successful and effective treatment of oesophageal GIST is surgical.
Another still controversial topic is the optimal surgical approach.
The choice of resection lies between oesophagectomy, associated with significant morbidity, and surgical tumour enucleation; both surgical approaches have been used in conjunction with molecular targeted therapy.1 3 4
Case presentation
A 70-year-old man was referred to our unit with an oesophageal lesion diagnosed incidentally.
He had a history of a parotid carcinoma treated by surgery 1 year before. During the follow-up period, he was diagnosed with a high uptake 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) oesophageal lesion (figures 1 and 2) on a PET (Standardized Uptake value Value 5.7).
Coronal and sagittal view of an FDG-PET showing a high-uptake FDG oesophageal lesion. FDG-PET, fluorodeoxyglucose positron emission tomography.
Axial view of an FDG-PET showing a high-uptake FDG oesophageal lesion. FDG-PET, fluorodeoxyglucose positron emission tomography.
No other medical or surgical history was referred.
Investigations
On endoscopic examination, we found a non-obstructing 40 mm subepithelial oesophageal lesion, no distinct mucosal abnormalities nor evidence of tumour. Endoscopic ultrasound (EUS) also showed a well-circumscribed tumour on the middle oesophagus, related to the muscularis propria. Fine-needle aspiration under EUS was done (figure 3) and immunohistochemistry on the tumour was positive for c-KIT (CD117) and DOG-1, highly likely to be a GIST.
Fine-needle aspiration under EUS of the oesophageal lesion. EUS, endoscopic ultrasound.
CT revealed no other lesions.
Treatment
The clinical case was discussed with a multidisciplinary team and he was proposed for a surgical approach.
An initial thoracoscopic approach was chosen with the need for conversion due to concerns about capsule integrity.
A left posterolateral thoracotomy on the fifth intercostal space confirmed a mass on the outer longitudinal muscle of the middle oesophagus. The tumour was easily removed from the surrounding tissue by a tumour enucleation procedure (figure 4). No oesophageal mucosa was injured.
The enucleated tumour with 45 mm size.
No intraoperative or postoperative complications occurred. With an unremarkable postoperative recovery, the patient was discharged on day 4.
Macroscopic examination found the enucleated tumour to be 45 mm in size, and no necrotic changes or mucosa ulceration were found. There was no evidence of capsule rupture. Immunohistochemistry was positive for c-KIT and overall microscopic findings confirmed the preoperative diagnosis of a low-grade GIST, with a mitotic rate of 2/5 mm2.
Outcome and follow-up
The patient was considered to have a low-risk GIST, according to tumour size, mitotic rate, location and absence of perforation.
He was evaluated at 2 months after surgery with no surgical complications or evidence of recurrence. He is currently under surveillance in an outpatient clinic every 6 months.
Discussion
The rarity of oesophageal GISTs results in a lack of clear recommendations concerning their optimal diagnostic approach and surgical management, providing a unique challenge.
International clinical guidelines for the management of GISTs have been published by both the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN). They are largely based on evidence coming from more commonly occurring gastric and small intestinal GISTs where malignant potential is known to vary with their size, mitotic index and anatomical location. There are no specific data or guidelines regarding the appropriate management of the oesophageal GISTs.
For this reason, as with most rare pathologies, many questions remain unanswered regarding their optimal management.
Endoscopic examination, EUS, CT and FDG-PET are used to diagnose, assess and stage GIST. However, it is difficult to determine preoperatively whether the tumour is benign or malignant by these imaging examinations. FNA biopsy under EUS provides important information preoperatively however it is often avoided with submucosal lesions. This is mainly due to two reasons: scarring could make enucleation more difficult and there is a potential risk of tumour dissemination by capsule destruction.3–6
Nevertheless, Robb et al reported a series of 16 oesophageal GISTs, 9 of which were submitted to a preoperative biopsy. They concluded that preoperative biopsy did not increase the risk of breach of tumour capsule nor increased postoperative morbidity.1
In our case, the GIST was reliably identified preoperatively by FNA without any side effects and providing one possible mean of differentiating oesophageal GISTs from other lesions. This helped us guide decisions regarding the necessity and radicality of resection.
There is consensus that oesophageal GIST, as with other GIST, should be treated with surgical resection.
The surgical approach, however, is controversial. In oesophageal GIST, surgical options are limited to enucleation (with high risk for R1 resection) and to oesophagectomy (with a high risk of morbidity).1 9
There is a strong correlation between the tumour size and performing esophagectomy. When tumours are large, the majority of surgeons elect to perform an oesophagectomy.2–7
Robb et al found that tumours of up to 65 mm in diameter, in the absence of mucosal ulceration, may be safely enucleated without compromising oncological outcomes.1
With regard to postoperative morbidity and mortality, tumour enucleation seems a better option, particularly in patients with comorbidities.1 7
In our case, enucleation was the chosen procedure for a 40 mm oesophageal GIST. An R0 resection was successfully achieved, without postoperative morbidity. The procedure was chosen based not only on the size of the tumour but also on the absence of mucosal ulceration and the patient’s individual surgical risk with consideration of underlying comorbidities and performance status.
Considering a non-surgical approach, imatinib, a Bcr-Abl tyrosine kinase inhibitor, has been shown to have high efficacy in the metastatic setting.
On an adjuvant setting, imatinib is now recommended as adjuvant therapy in patients with a high risk of relapse, particularly those with high-risk tumours (according to the modified National Institute of Health classification) by the ESMO and NCCN guidelines.6 7
There is little evidence based on clinical trials concerning neoadjuvant imatinib therapy for GISTs. Downsizing of GIST by preoperative administration of imatinib seems attractive to reduce the extent of resection, especially when R0 surgery implies major functional sequelae and affect the postoperative quality of life in these patients.6
Kang et al suggested that neoadjuvant imatinib treatment can be considered in patients with high mitotic rates and/or larger tumour sizes to obtain negative microscopic margins (R0 resection) and to reduce the risk of intraoperative complications, including tumour rupture.4
When approaching an oesophageal GIST a multidisciplinary treatment planning is needed. Management should be carried out in reference centres for sarcomas and GISTs and/or within reference networks sharing multidisciplinary expertise and treating a high number of patients annually.8
Learning points
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Oesophageal gastrointestinalstromal tumours (GISTs) are extremely rare tumours.
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Where there is diagnostic doubt, tumour fine needle biopsy may be performed without compromising resection or outcomes.
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Surgical resection is the only curative treatment for localised oesophageal GISTs.
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Enucleation without rupture of the tumour capsule is achievable.
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Multidisciplinary treatment planning is needed.
Footnotes
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Contributors All the authors were involved on the clinical case, during surgery and patient follow up. All were responsible for conception of the work. FC and RC were involved in planning and supervised the work. FC were responsible for drafting the article and took the lead in writing the manuscript. CM and PR did a critical revision and editing. RC discussed the results and provided critical feedback.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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