Gastrointestinal stromal tumor (GIST) is one of the most common types of submucosal tumors (SMTs). Because of GIST’s malignant potential, it is crucial to differentiate it from other SMTs. The present study aimed to identify characteristic endoscopic findings of GISTs in the small intestine.
We reviewed the clinicopathological and endoscopic findings of 38 patients with endoscopically or surgically resected SMTs in the small intestine. SMTs were classified into GIST and non-GIST groups, and clinicopathological and endoscopic findings were compared between the 2 groups.
Fifteen patients had GIST and 23 patients had other types of SMTs in the small intestine. Comparison of the endoscopic findings between the 2 groups revealed that dilated vessels in the surrounding mucosa were significantly more in number in the GIST group than in the non-GIST group (
Dilated vessels in the surrounding mucosa, identified during balloon-assisted endoscopy, may be a diagnostic indicator for GIST in the small intestine. However, its clinical significance should be further analyzed.
Gastrointestinal stromal tumor (GISTs) is a mesenchymal tumor of the GI tract, with the small intestine being the second most frequent location, accounting for 20%–30% of all GISTs [
Recent developments in balloon-assisted endoscopy (BAE) and capsule endoscopy have enabled the endoscopic observation of small intestinal pathologies. BAE is particularly useful for diagnosing tumorous lesions in the small intestine by allowing precise observation and bioptic examination. However, it is often difficult to make a pathological diagnosis of submucosal tumor (SMT) by bioptic examination under BAE [
This study included 38 cases with small intestinal SMTs found by BAE and endoscopically or surgically resected between September 2004 and October 2018. One case was treated by endoscopic mucosal resection and 37 cases underwent surgical resection. The clinical data of each patient were obtained by review of patient records at Kyushu University Hospital, and included information on gender, age, clinical symptoms, and laboratory data, including hemoglobin, lactate, and dehydrogenase at the time of BAE. Contrast-enhanced CT (CE-CT) findings were also reviewed for patients with small intestinal GISTs. Histopathological diagnosis of the small intestinal SMT was confirmed in all cases, and it was determined by 3 pathologists (Y.I., M.E., and H.Y.) based on H&E staining and immunohistochemical staining, as required.
The study protocol was approved by the ethics committee at Kyushu University Hospital (IRB No. 30-485), and the study was conducted in accordance with the Helsinki Declaration. Informed consent was obtained from all patients.
BAE was performed using a Double-Balloon Endoscopy System (Fujinon-Toshiba ES System Co., Tokyo, Japan). Antegrade and retrograde BAE were performed as described previously [
The BAE images were retrospectively reviewed by 2 expert endoscopists (Y.I. and T.T.). The following endoscopic findings were determined: color of the tumor surface (yellowish, bluish, reddish, or same as the surrounding mucosa), nodularity of the tumor (smooth or multinodular), presence of ulcer (none, single, or multiple), and abnormality of the surrounding mucosa (dilated vessels). Disagreements regarding the endoscopic findings were resolved by discussion between the 2 endoscopists. Because endoscopic determination can underestimate the tumor size of small bowel SMTs, the tumor size was determined based on the endoscopically or surgically resected specimens.
Categorical variables were described as frequencies and numerical variables as median (range). Clinicopathological and endoscopic findings were compared between the groups using Fisher exact probability test or Wilcoxon signed-rank test, as appropriate. All statistical analyses were performed using JMP Pro11 (SAS Institute Inc., Cary, NC, USA). A
Of the 38 patients, 15 were diagnosed with GIST (GIST group) and the remaining 23 patients were diagnosed with small intestinal SMT other than GIST (non-GIST group). In the non-GIST group, malignant lymphoma manifesting SMT like mass was found in 16 patients, neuroendocrine tumors in 2 patients, heterotopic pancreas in 2 patients, leiomyosarcoma in 1 patient, dedifferentiated liposarcoma in 1 patient, and metastatic tumor in 1 patient. Histological types of malignant lymphoma included follicular lymphoma (n=5), mucosa-associated lymphoid tissue lymphoma (n=2), diffuse large B-cell lymphoma (n=5), Burkitt lymphoma (n=1) or T-cell lymphoma (n=3). The clinical characteristics of the GIST and non-GIST groups are compared in
Twenty-four of the 38 patients underwent antegrade BAE, 12 underwent retrograde BAE, and the remaining 2 patients underwent both antegrade and retrograde BAE. GISTs were found in the jejunum in 12 patients and the ileum in 3 patients, and small intestinal non-GISTs were located in the duodenum in 1, the jejunum in 13, and the ileum in 9 patients. The sites of the lesions were not significantly different in the 2 groups (
The endoscopic findings in the GIST and non-GIST groups are compared in
There was no significant difference in the incidence of hematemesis or melena between GIST patients with and without dilated vessels. There was also no difference in median hemoglobin values between GIST patients with dilated vessels (13.2 g/dL [range, 6.3–16.1 g/dL]) and those without (12.4 g/dL [range, 8.9–14.7 g/dL]). However, one patient with GIST accompanied by dilated vessels developed hemorrhagic shock after bioptic examination under double-balloon endoscopy.
The histological features of GISTs with and without dilated vessels are compared in
Histological confirmation is crucial for making treatment decisions in patients with GI tumorous lesions, particularly in the case of malignant tumors such as GIST. However, it may be difficult to obtain tumor biopsies from GISTs because of their configuration. The rate of histological diagnosis of GIST by enteroscopy was previously reported to be only 40%–45% [
We only recruited cases with small intestinal SMTs that had been endoscopically or surgically resected in the present study. This is because precise determination of tumor size is indispensable for the analysis of endoscopic findings of small intestinal SMTs, and because endoscopy can underestimate the tumor size when the tumor shows an eccentric extraluminal growth pattern. Consequently, non-GIST group was mostly composed of malignant lymphoma that shows endoscopic variation such as ulcerative, nodular (including SMT like mass), infiltrative or diminutive mucosal changes. Malignant lymphoma manifesting SMT like mass alone was included in the non-GIST group considering the aim of the present study.
The present study revealed no differences in color, nodularity, size, or presence of ulcers on the tumor surface between GISTs and other SMTs. It thus can be considered that central umbilication, ulceration of the overlying mucosa, or multiple nodularity were not the diagnostic clues for differentiating GIST from other malignant SMTs including malignant lymphoma, neuroendocrine tumors, and metastatic tumor, while such findings are indicated as diagnostic hints for malignant SMTs. However, dilated vessels in the surrounding mucosa were significantly more frequent in GISTs than in other small intestinal SMTs, suggesting that this endoscopic findings might be a clue to a diagnosis of small intestinal GIST under BAE.
Fukuta et al. [
We also analyzed the clinical impact of the endoscopic findings by comparing clinical symptoms and the risk of bleeding caused by bioptic examination. Two previously reported cases presented with overt GI bleeding as the initial clinical symptom of small intestinal GISTs [
The present study had several limitations. First, the number of subjects was small, which might have affected the statistical analysis. Second, it was a retrospective study with limited clinical data, and the possibility of selection bias cannot be excluded. Furthermore, it was difficult to evaluate the histological findings of small intestinal SMTs in relation to the surrounding mucosa, including the presence of dilated vessels.
In conclusion, the presence of dilated vessels in the surrounding mucosa may be an endoscopic clue for differentiating between GIST and other SMTs in the small intestine. Further studies with larger numbers of subjects with a variety of small bowel SMTs are needed to confirm the clinical impact of this endoscopic finding in small intestinal GISTs.
The authors received no financial support for the research, authorship, and/or publication of this article.
No potential conflict of interest relevant to this article was reported.
Original draft: Esaki M. Endoscopy: Torisu T, Moriyama T, Umeno J, Hirano A, Okamoto Y, Esaki M. Pathological diagnosis: Hori Y, Yamamoto H. Writing: Ihara Y. Analysis: Ihara Y. Review: Torisu T, Moriyama T, Umeno J, Hirano A, Okamoto Y, Kitazono T, Esaki M. Editing: Torisu T, Esaki M. Approval of final manuscript: all authors.
Double-balloon endoscopy images of gastrointestinal stromal tumor. (A) Multinodular submucosal tumor with tortuous dilated vessels. (B) Blue dilated vessels on the surface of the tumor and surrounding mucosa.
Representative images of submucosal tumor other than gastrointestinal stromal tumor. (A) Follicular lymphoma. (B) Mucosa-associated lymphoid tissue lymphoma. (C) Diffuse large B-cell lymphoma. (D) T-cell lymphoma. (E) Heterotopic pancreas. (F) Dedifferentiated liposarcoma.
Clinical Features of Patients with GISTs and Non-GIST SMTs in the Small Intestine
Characteristic | GIST group (n=15) | Non-GIST group (n=23) | |
---|---|---|---|
Sex (female/male) | 6/9 | 13/10 | 0.508 |
Age (yr) | 65 (40–82) | 66 (34–80) | 0.846 |
Symptoms | |||
Abdominal pain | 5 | 10 | 0.736 |
Abdominal distension | 4 | 5 | 1.000 |
Hematemesis or melena | 4 | 5 | 0.451 |
None | 6 | 7 | 0.728 |
Hemoglobin (g/dL) | 12.6 (6.3–16.1) | 12.2 (8.1–15.6) | 0.487 |
LDH (g/dL) | 190 (141–411) | 194 (128–529) | 0.811 |
Pathology | |||
GIST | 15 | ||
Malignant lymphoma | 16 | ||
Follicular | 5 | ||
MALT | 2 | ||
DLBCL | 5 | ||
Burkitt | 1 | ||
T-cell | 3 | ||
Neuroendocrine tumors | 2 | ||
Heterotopic pancreas | 2 | ||
Leiomyosarcoma | 1 | ||
Dedifferentiated liposarcoma | 1 | ||
Metastasis tumor | 1 |
Values are presented as number or median (range).
GIST, GI stromal tumor; SMT, submucosal tumor; MALT, mucosa-associated lymphoid tissue; DLBCL, diffuse large B-cell lymphoma.
Endoscopic Findings in Patients with GISTs and Non-GIST SMTs in the Small Intestine
Characteristic | GIST group (n=15) | Non-GIST group (n=23) | |
---|---|---|---|
Tumor size (mm) | 32 (22–95) | 60 (5–300) | 0.193 |
Color | |||
Yellowish | 0 | 1 | 1.000 |
Bluish | 1 | 0 | 0.395 |
Reddish | 0 | 5 | 0.137 |
Similar to the surrounding mucosa | 14 | 17 | 0.209 |
Nodularity | 0.508 | ||
Smooth protrusion | 9 | 10 | |
Multinodular protrusion | 6 | 13 | |
Ulcer | 0.453 | ||
None | 8 | 8 | |
Single | 6 | 14 | |
Multiple | 1 | 1 | |
Surrounding mucosa | |||
Dilated vessels | 7 | 0 | < 0.001 |
Values are presented as number or median (range).
GIST, GI stromal tumor; SMT, submucosal tumor.
Pathological Findings of GISTs with and without Dilated Vessels
Dilated vessels group (n=7) | Without dilated vessels group (n=8) | ||
---|---|---|---|
Tumor size (mm) | 28 (25–95) | 40 (22–75) | 0.486 |
Tumor growth pattern | 0.405 | ||
Intramural | 1 | 3 | |
Extramural | 2 | 3 | |
Intraluminal | 4 | 2 | |
Mib-1 index |
4.27 ± 4.15 | 3.22 ± 3.26 | 0.771 |
Miettinen classification | 0.978 | ||
Low | 4 | 5 | |
Intermediate | 1 | 1 | |
High | 2 | 2 | |
Metastasis at diagnosis | 1 | 0 | 0.467 |
0.467Values are presented as median (range), number, or mean±SD.
Mib-1 index was determined by observing 1,000 nuclei in areas of the section with the highest labelling rates.
GIST, GI stromal tumor.