Surg Today DOI 10.1007/s00595-014-0929-x


Giant esophageal gastrointestinal stromal tumor: report of a case Akira Nakano • Yasunori Akutsu • Kiyohiko Shuto • Masaya Uesato • Tsuguaki Kono • Isamu Hoshino • Naoki Akanuma • Tetsuro Maruyama Yuka Isozaki • Hisahiro Matsubara

Received: 16 December 2012 / Accepted: 5 November 2013 Ó Springer Japan 2014

Abstract Gastrointestinal stromal tumors (GISTs) rarely arise in the esophagus, where carcinoma is the most common malignant neoplasm and leiomyoma is the most common benign tumor. Because of their rarity, the clinical course and treatment of esophageal GISTs are poorly understood. These lesions are generally thought to carry a poor prognosis, making the differential diagnosis of other common mesenchymal neoplasms essential, for both prognostic and therapeutic reasons. We report a case of successfully resected giant esophageal GIST, thought to be the largest resected GIST reported in Japan. The patient was a 65-year-old woman, in whom upper gastrointestinal endoscopy found a 180-mm submucosal tumor in the lower thoracic esophagus, extending just below the aortic arch. We diagnosed esophageal GIST, and the patient underwent middle and lower esophagectomy via left thoracotomy, followed by gastric tube reconstruction. The tumor was resected completely. Histopathological and immunohistochemical staining confirmed that the tumor was a high-risk lesion, and treatment with imatinib was initiated. Computed tomography showed liver metastasis 5 months later, but the patient is doing well 24 months after surgery. Keywords Gastrointestinal stromal tumor  Esophagus  Prognostic factor

A. Nakano (&)  Y. Akutsu  K. Shuto  M. Uesato  T. Kono  I. Hoshino  N. Akanuma  T. Maruyama  Y. Isozaki  H. Matsubara Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan e-mail: [email protected] Y. Akutsu e-mail: [email protected]

Introduction Gastrointestinal stromal tumors (GISTs) primarily arise in the stomach (50 %), followed by the small intestine (25 %), then the colon and rectum (10 %). GISTs rarely arise in the esophagus, with a reported frequency of \5 % [1, 2]. In contrast, the most common mesenchymal tumors of the esophagus are leiomyomas [3, 4]. Making a preoperative diagnosis of esophageal GIST is difficult. Performing a tumor biopsy is not recommended, as the risk of tumor dissemination increases if the tumor capsule is destroyed. Moreover, performing segmental or wedge resection with an adequate safety margin, the recommended surgical treatment for GISTs, is very difficult for esophageal GISTs [5]. As the type of surgery (esophagectomy or enucleation) depends on the diagnosis, the clinical features of patients with esophageal GISTs must be studied further. We report a case of successfully resected giant esophageal GIST, thought to be the largest resected GIST reported in Japan. Following this report, we review the relevant literature and discuss the clinical and pathological features of this disorder.

Case report A 65-year-old woman was referred to our hospital for investigation of dysphagia. Blood biochemistry showed almost normal results; however, a barium swallow study revealed a smooth and round defect in the left wall of the esophagus, suggesting a submucosal tumor (Fig. 1a). On endoscopic examination, we found a tumor covered with apparently normal mucosa located 32–42 cm from the incisor teeth. Computed tomography (CT) also showed a solid tumor, approximately 16 cm in size, extending from


Surg Today Fig. 1 a Barium esophagography showed a smooth and round defect in the left wall of the lower third of the esophagus (arrow). b Computed tomography (CT) showed a solid 16-cm tumor, extending from the upper thoracic esophagus to the partial abdominal esophagus

the upper thoracic esophagus to the abdominal esophagus, without obvious associated mediastinal lymphadenopathy (Fig. 1b). Positron emission tomography (PET) revealed high uptake of FDG in the same region, with a standardized uptake value (SUV) of 16.7. Pathological examination of a biopsy specimen obtained by a boring biopsy revealed atypical cells, and immunohistochemistry was negative for c-KIT, CD34, S-100, and desmin. Based on the patient’s clinical course and the findings of the examinations, a primary esophageal GIST was suspected, although a definitive diagnosis was not made preoperatively. Surgery The patient underwent middle and lower esophagectomy via left thoracotomy and laparotomy through a continuous incision from the fifth intercostal space to the upper midline of the abdomen. The tumor was adhered to adjacent organs, including the lungs, pericardium, aorta and diaphragm. The upper side of the tumor was located just under the aortic arch. However, curative resection followed by gastric tube reconstruction was achieved.

positivity for c-KIT, CD34 and Ki-67 and negativity for SMA (Fig. 2c, d, e, f). The MIB-1 labelling index was more than 40 % of the tumor cells. Based on these results, a final diagnosis of an esophageal GIST with a high malignant potential was made. Postoperative course The patient’s postoperative course was uneventful and she was discharged from hospital on postoperative day 36. The tumor was defined as a high-risk lesion according to the consensus guidelines. Adjuvant chemotherapy with imatinib mesylate was recommended based on the histological findings and this was commenced 2 months after surgery; however, 1 month later, the imatinib treatment was discontinued because of adverse effects, including nausea, anemia, and flaring. Follow-up CT, 5 months after surgery, showed liver metastasis and the imatinib was restarted. The liver metastasis liquefied following the re-administration of imatinib. The patient is now doing well, 24 months after surgery.

Pathological findings


The resected tumor measured 180 9 150 9 80 mm and contained an ulcer of approximately 2 cm on the mucosa (Fig. 2a). Necrotic changes were observed on the cut surface. The microscopic findings of hematoxylin–eosin staining showed a bundle-like growth of spindle-shaped tumor cells (Fig. 2b), with a mitotic rate of 50/50 high power fields (HPF). The tumor size and mitotic index indicated that the tumor had high malignant potential. Immunohistochemical staining of the tumor cells revealed

GISTs belong to a large group of mesenchymal spindlecell tumors of the digestive tract and are often classified according to Rosai’s classification based on immunohistochemical studies. The most definitive feature of GISTs is the expression of c-kit, and GISTs that do not exhibit cell differentiation into smooth muscle or nerve cells are classified as the ‘‘uncommitted type’’ according to Rosai’s classification [6–9]. Most GISTs originate in the stomach or small intestine; however, esophageal GISTs are very


Surg Today

Fig. 2 a The resected tumor measured 180 9 150 9 80 mm with an ulcer of approximately 2 cm on its mucosa. b–e Histopathological examination revealed a bundle-like growth of spindle-shaped tumor cells (hematoxylin and eosin stain). b Immunohistochemical analysis

revealed that the tumor cells exhibited a KIT expression (immunohistochemical stain for KIT) (c) and were positive for CD 34 (d) and negative for SMA (e). The Ki-67 expression was strongly positive (f)

rare, accounting for as few as 1–3 % of all GISTs [7]. Therefore, only a small number of cases of esophageal GIST have been reported, and the characteristics of these lesions remain unclear. We searched for and reviewed all case reports of uncommitted type GISTs originating in the esophagus, published between January 1983 and May 2011 in the database of the Japan Medical Abstracts Society and PubMed using the key words, ‘‘esophagus (oesophagus),’’ ‘‘gastrointestinal stromal tumor’’ and ‘‘GIST’’. We eliminated case reports thought to be about leiomyoma or other types of mesenchymal tumors when possible, so that each case report was acceptable based on the PRESENT definition of ‘‘uncommitted type’’ GIST. A total of 153 cases reports were found (136 cases in the Japan Medical Abstracts Society database and 17 cases in

PubMed). The clinical features of these cases are summarized in Table 1. The 153 patients included 90 women (58.8 %, n = 153) and 63 men (41.2 %, n = 153), with a male: female ratio of 1:1.4. The mean age of the patients was 61.0 years, with a range of 18–87 years. The frequency of GISTs increased with age, occurring most frequently between the ages of 60 and 70 years, unlike the trend for esophageal cancer. The chief complaint varied according to the site and tumor size. The most common symptom was dysphagia (36.2 %), followed by chest pain (8.5 %), odynophagia (3.5 %), and mucosal bleeding from ulcerations (1.4 %). Since many of the tumors were detected incidentally before becoming symptomatic, there were 69 (48.9 %, n = 141) patients with no symptoms. The esophageal GISTs were located in


Surg Today Table 1 Clinical features of esophageal gastrointestinal tumors (GISTs; n = 135) Factors

Population (%)

Gender Male Female Age

63 (41.1) 90 (58.9) 61.03 ± 13.08


1 (0.7)


16 (10.6)

41–60 61–80

44 (29.1) 84 (55.6)


6 (4.0)

Location Celvical

0 (0.0)

Upper thoracic

7 (5.3)

Middle thoracic

33 (24.8)

Lower thoracic

70 (52.7)


23 (17.2)

Symptoms No compliment

69 (48.9)


51 (36.2)

Chest pain

12 (8.5)


5 (3.6)

Mucosal bleeding

2 (1.4)


2 (1.4)

Size of tumor

72.7 ± 40.6

*30 mm

22 (17.3)

31–60 mm

38 (29.9)

61–90 mm

25 (19.7)

91–120 mm

23 (18.1)

121–150 mm

16 (12.6)

151–180 mm 181 mm*

2 (1.6) 1 (0.8)

the upper thoracic in 7 patients (5.3 %, n = 133), the middle thoracic esophagus in 33 patients (24.8 %), the lower thoracic esophagus in 70 patients (52.7 %), the abdominal esophagus in 23 patients (17.2 %), and the cervical esophagus in 0 patients. The largest tumor size ranged between 30 and 60 mm, but only 28 patients (21.8 %, n = 127) had a tumor[10 cm n = 127) and only 3 patients had a tumor [15 cm (6.3 %). Thus, the present case represents the largest reported GIST in Japan and the second largest worldwide [10]. Whether esophageal masses should be biopsied preoperatively remains controversial. Some authors have suggested that GISTs may be reliably diagnosed using EUSguided fine-needle aspiration (FNA) [11, 12]. However, GISTs are fragile and the use of FNA could increase the


risk of tumor dissemination. Therefore, performing preoperative biopsies of resectable masses is not recommended in the National Comprehensive Cancer Network guidelines [13]. Conversely, in some cases, conducting an immunohistochemical assessment is necessary to obtain a preoperative diagnosis. In the series of cases we reviewed, preoperative biopsies were performed in 73 patients, with GISTs diagnosed in 40 (55.6 %, n = 73). The treatment options for GISTs include complete surgical resection and pharmacologic therapy, although resection of the primary tumor is considered definitive. While esophageal cancer commonly spreads aggressively through the lymphatic system [14], lymph node metastases from GISTS are rare, and local resection has often been reported to be sufficient [15]. Of the 153 patients, 139 (87.4 %) underwent surgery, which was often complete resection. Among these 139 patients (87.4 %), recurrence was detected later in 23 (16.5 %), as local recurrence in 5 (3.6 %) and as metastasis in 18 (12.9 %). The overall survival (OS) and disease-free survival (DFS) times were documented for 79 of the 139 patients who underwent surgery and we analyzed their prognoses. The median interval to recurrence was 40 months, the 5-year OS rate was 88.7 %, and the 5-year DFS rate was 57.0 % (Fig. 3). Esophageal GISTs have a tendency to recur at a constant rate after surgery, even 5 years or more after surgery, unlike esophageal carcinoma. These results indicate that esophageal GISTs require long-term follow-up. The mitotic index and tumor size have been established as prognostic indicators for GISTs of the stomach [12]. To further identify the prognostic indicators for esophageal GISTs, we analyzed the 5-year OS and DFS rates. All patients were dichotomized into groups according to age (under or over 65 years), gender, tumor size (within or over 5 cm), mitosis (more or less than 10/50HPF), and positivity or negativity for SMA and S-100. We then calculated the cumulative OS and DFS rates, using the Kaplan–Meier method. P values of\0.05 were considered significant. The results are shown in Table 2. No significant differences were observed in 5-year OS between the groups in any category; however, significant differences were found in 5-year DFS between patients under and those over 65 years of age (p value 0.302), between men and women (p value 0.003), and between patients with a primary tumor size of within 5 cm and those with a tumor size [5 cm (p value 0.030). Moreover, a mitosis rate of more or less than 5/50 HPF had a p value of 0.023, and SMA (?) and (-) and S-100 (?) and (-) had p values of 0.361 and 0.169, respectively. These findings indicate that gender, mitosis rate, and tumor size are prognostic indicators for esophageal GIST. Based on these results, the question arises as to why the DFS, but the not OS, is significantly increased in patients with a lower mitotic index and smaller tumor size,

Surg Today Fig. 3 Overall survival and disease-free survival rates

Table 2 Analysis of 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates

Category Age Gender

5-year OS(%)

\65 years



65 yearsB









Size of tumor

\5 cm


5 cmB


Mitosis rate












SMA S-100 * Significant

Pt. number





as the mitosis rate and tumor size are used to predict the risk of recurrence in patients with gastric GISTs [16–19]. If the same DFS trend is observed in patients with esophageal GISTs, why not the OS? It is still possible that the small number of cases in which recurrence was found is not adequate for significant differences in OS to be detected between the two groups. Further studies involving more patients are needed to resolve why the OS and DFS exhibit marked contrast between males and females. Since esophageal GISTs are rarely reported, there has been little analysis of these lesions in the literature. However, research regarding adjuvant/neoadjuvant chemotherapy is advancing, and some regimens have been shown to be effective. Therefore, the clinical features and prognosis of patients with esophageal GISTs must be fully investigated. Our study demonstrated some clinical features and tendencies regarding recurrence and our findings in all regards suggest that long-term follow-up is required for patients with esophageal GISTs. Ultimately, further studies of more patients are needed.


P value 0.197 0.453

Conflict of interest





83.9 0.921



55.4 1.000



38.3 0.486

82.6 64.3

P value




5-year DFS(%)



62.5 0.755




We have no conflicts of interest to disclose.

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Giant esophageal gastrointestinal stromal tumor: report of a case.

Gastrointestinal stromal tumors (GISTs) rarely arise in the esophagus, where carcinoma is the most common malignant neoplasm and leiomyoma is the most...
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