Gastrointestinal stromal tumors (GISTs) are defined as mesenchymal neoplasms arising from the digestive tract and abdomen [1]. GISTs occur primarily in the stomach and small intestines. Among GISTs, esophageal GIST is a rare subtype [2,3]. Compared with gastric GISTs, esophageal GISTs are rare, and diagnostic and treatment guidelines are still lacking [4].

GISTs are positive for c-KIT (CD117) or CD34. They are believed to originate from interstitial cells of Cajal (ICCs) [5]. Leiomyomas are the most common esophageal mesenchymal neoplasms. GISTs can be distinguished from leiomyomas by immunohistochemical staining for c-KIT and CD34 [6].

Reports of esophageal GISTs are rare. There have been few reports of a fast-growing stomach GIST [7], reports of esophageal GISTs increasing in size are even rarer [8]. Herein, we report a case of esophageal GIST with a sharp increase in size over a short period of time [9].

A 54-year-old woman visited our outpatient clinic with dysphagia for one month. Her dysphagia has become worse with time. She vomited after just drinking water and felt dyspnea from a week ago. She had no specific past medical history. Five months ago, no protruded lesion in the lower esophagus was observed in the esophagogastroduodenoscopy (EGD) (Fig. 1A). However, the EGD performed at the primary hospital this time showed a huge elevating esophageal subepithelial lesion (SEL).

At the time of admission, her vital signs were as follow: blood pressure, 105/70 mm Hg; pulse, 75 beats per minute; respiratory rate, 20 times per minute; and temperature, 36.5°C. Her physical examination and chest X-ray were unremarkable. There was no specific abnormal finding on the electrocardiogram. Her amylase count was 582 U/L (reference: 12–53 U/L), which was high. However, her other laboratory test results were normal.

The EGD performed in our clinic showed a round protruding lesion having a size of about 40×30 mm sized with a normal overlying mucosal surface at 35 cm to 39 cm from the upper incisor (Fig. 1B). Endoscopic biopsy was performed on the lesion observed in the esophagus, and the pathologic result was “mature squamous epithelium.” In addition to EGD, endoscopic ultrasound (EUS) was performed. EUS showed a round hypoechoic heterogenous well marginated lesion with a size of 49.0×54.6 mm arising from the muscularis propria layer with focal hypoechoic areas suspicious for necrosis (Fig. 1C). Chest computed tomography (CT) scan revealed a smooth, relatively homogeneous mass having a size of 8.5×5.3×7.0 cm with a slightly enhancement at the distal esophagus. The mass of esophagus appeared to press the heart. It was thought to be related to symptoms of dyspnea that the patient complained of (Fig. 1D). The patient was referred to department of thoracic surgery. It was decided that surgery would be performed for diagnostic and therapeutic purposes. Enucleation operation was performed for the esophageal mass. The resected specimen was measured to be 8.5×7.7×5.7 cm in size (Fig. 2A). Immunochemical test revealed that the resected specimen was positive for c-KIT (Fig. 2B) and CD34 (Fig. 2C). The mass invaded mucosa (Fig. 2D). Its mitosis rate was higher than 10 instances of mitosis per 50 high-power fields (HPFs). Necrosis was present in the histopathological examination. The patient was diagnosed with esophageal GIST with a high risk based on all examination results. After esophageal GIST with a high risk was confirmed, we performed F-18 positron emission tomography-CT (F-18 PET-CT), which showed localized hypermetabolic lesion in the lower thoracic esophagus. It was considered to be caused by postoperative inflammation (Fig. 3A). A follow-up EGD and chest CT were performed at two months after the surgery, showing no recurrence of the esophageal GIST. Therefore, imatinib mesylate was started to reduce the recurrence of esophageal GIST. EGD (Fig. 3B) and chest CT (Fig. 3C) at 8 months postoperatively showed no recurrence. The patient was stable without recurrence at 10-month follow-up.

Mazur and Clark [1] first used the term GISTs in 1983. GISTs are defined as mesenchymal neoplasms arising from the digestive tract and abdomen [1]. A lesion below the submucosal layer that protrudes as a gastrointestinal tract is a typical endoscopic finding of esophageal GIST. If the size of tumor is large, mucosal change and ulcerations are more frequently accompanied. Choe et al. [10] reported that “common SELs in the esophagus were leiomyoma (75.8%) and granular cell tumor (15.2%).” Due to the location and the rarity of esophageal GIST, it is difficult to determine the type of mass or whether it is malignant or benign using imaging examinations. EUS can be used for diagnosing esophageal GISTs, which are usually hypoechoic lesions originating from the muscularis propria layer. High-risk stigmata of GIST on EUS includes a presence of cystic spaces, irregular margin, tumor size >3 cm, heterogeneous echogenecity [11]. CT can be used for determining the localization and stage of these lesions. In this case, the size of GIST was different on EUS and CT. The reason for this is thought to be that EUS can only be evaluated in two dimensions, unlike CT, which can be evaluated in three dimensions. F-18 PET-CT can also be used to diagnose GIST. It can help assess treatment response [12,13].

Histological confirmation is important for accurate diagnosis of GIST. However, due to the configuration of GIST, it is difficult to obtain sufficient tissues with endoscopic biopsy. EUS guided fine needle aspiration and EUS guided fine needle biopsy show high diagnostic accuracy [12,14]. Immunohistochemical staining is also needed for the diagnosis of GIST. c-KIT is the most important immunohistochemical staining method for GIST diagnosis. More than 95% of GISTs are positive for KIT protein [15]. GISTs are believed to originate from ICCs. In the gut, ICCs are the only cells that are KIT+CD34+Vim+im munoreactive [5,16,17]. Although ICC tumors can be demonstrated by their KIT immunoreactivity, CD34 as a specific marker in ICCs should be used together for identifying ICC tumors [18,19]. In addition to immunohistochemical staining, the diagnosis of GIST is often suspected histologically because most cases show uniform findings in three categories: spindle cell type (70%), epithelioid type (20%), and mixed type [20]. GISTs occur primarily in the stomach (60%) and small intestines (35%). Esophageal GISTs account for less than 2% of total GISTs [3]. As such, esophageal GIST is a rare subtype among GISTs. The incidence of esophageal GISTs is about 0.1 to 0.3 per million people [2]. In Korea, the first case of esophageal GIST was reported in 2009. Since then, a few cases have been reported [6,21,22].

Esophageal GISTs are rare diseases and mostly asymptomatic and accidentally detected in routine examinations. When the tumor grows, patients may present with symptoms which can vary depending on the location and size of the tumor. Dysphagia (23%), pain (19%), reflux (15%), and bleeding (8%) are the most common symptoms. Cough, fatigue, dyspnea, and weight loss are also possible, although they are reported less frequently [13,23].

Complete surgical resection is the standard treatment for primary resectable GISTs [24]. Microscopically nonradical (R1) resection is associated with a higher disease recurrence than microscopic radical resection (R0) (5-year disease free survival rate: 29.5% [95% confidence interval, CI: 15.7–43.4] vs. 40.5% [95% CI: 30.8–50.3], respectively) [25]. Unlike GISTs in other locations, resection of esophageal GISTs is limited to simple enucleation or esophagectomy. If the tumor is larger than 2 cm or involves gastroesophageal junction, esophagectomy is recommended. If the tumor is smaller than 2 cm and confined to the esophageal wall, especially in patients who cannot tolerate esophagectomy, enucleation is recommended if a margin-negative resection is possible [26].

Because the activation of KIT, which is one of the receptor tyrosine kinases, occurs in most cases of GISTs, inhibiting KIT is becoming as a major treatment method along with surgery. Imatinib mesylate is a selective inhibitor of KIT protein tyrosine kinase. Several studies have consistently reported the efficacy of imatinib mesylate in GIST patients [27,28]. In 2002, the FDA approved imatinib mesylate for treating patients with unresectable and/or malignant metastatic GIST [29]. Fiore et al. [30] showed that using preoperative imatinib mesylate could improve resectability and surgical morbidity. However, preoperative imatinib mesylate can increase the fragility of GIST by leading to tumor necrosis or cystic change, which can cause bleeding or rupture. Therefore, surgery after imatinib mesylate use should be performed by surgeons with extensive experience in GISTs [31]. Previous studies have reported that postoperative imatinib mesylate is associated with improved relapse-free survival and overall survival [32]. NCCN guidelines recommend the use of postoperative imatinib mesylate for at least 36 months in patients with high risk GISTs (tumor >5 cm in size, mitotic rate >5 mitoses/50 HPFs) [32]. The follow-up interval should be adjusted according to the risk of recurrence predicted using a risk estimation tool such as a modified National Institutes of Health scheme, the Armed Forces Institute of Pathology scheme, and prognostic heat maps. For high-risk patients, abdominal CT or magnetic resonance imaging every six months for the first five years and follow-up every year for the next five years are required [33].

To the best of our knowledge, this is the fifth case of esophageal GIST in Korea (Table 1), and the second reported case of esophageal GIST with a sharp increase in size. In the present case, there was no specific finding in EGD performed at five months before the onset of symptoms, although a mass filled with lumen was observed in the EGD after five months. Additionally, the size of mass increased further after one month.

In conclusion, keeping in mind that the size of esophageal GIST can increase rapidly, endoscopic follow-up is necessary if patient symptoms show changes, even if there is no specific finding in recent EGD.