The malignancy among gastric submucosal tumor
Review Article

The malignancy among gastric submucosal tumor

Bin Yang, Xinliang Lu

Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China

Contributions: (I) Conception and design: All authors; (II) Administrative support: X Lu; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: B Yang; (V) Data analysis and interpretation: B Yang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Dr. Xinliang Lu. Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China. Email: lux@zju.edu.cn.

Abstract: The origin and characteristics of most submucosal tumors (SMTs) cannot easily be confirmed by gastrointestinal endoscopy or other radiological examinations. Excluding GISTs, for those other gastric SMTs, most of which are deemed benign, the necessity and timing of intervention has been ignored. Thus, the malignancy of gastric SMTs still remains unknown. In order to summarize the malignancy of these gastric SMTs, we reviewed literatures and analyzed cases of gastric SMTs including heterotopic pancreas, leiomyoma, schwannoma, glomus tumor, hemangioendothelioma, granular cell tumor (GCT), lipoma, hemangiopericytoma, lymphangioma and neurofibroma. In these literatures, there are cases of malignancy among heterotopic pancreas, leiomyoma, schwannoma, glomus tumor, hemangioendothelioma and GCT. As a result, it suggests that although most of gastric SMTs are considered benign, there are still possibilities of malignancy, which requires our attention, even active intervention and long-term follow-up.

Keywords: Gastric submucosal tumor (gastric SMT); malignancy

Submitted Jun 03, 2019. Accepted for publication Oct 10, 2019.

doi: 10.21037/tcr.2019.10.41

Introduction

The submucosal tumor (SMT), or subepithelial tumor (SET), is clinically common protuberant lesions or lumps covered with intact mucosa (1). The origin and characteristics of most SMTs cannot easily be confirmed by gastrointestinal endoscopy or other radiological examinations. These SMTs can be divided into mesenchymal tumors and non-tumorous submucosal lesions (2). And the mesenchymal tumors include benign, borderline malignant and malignant tumors (3). The majority of SMTs seldom cause symptoms, but are detected incidentally by endoscopic or radiologic examinations (4).

As is known to all, gastrointestinal stromal tumor (GIST) has been already widely studied. There are relatively reliable guidelines for the diagnosis and treatment of gastric GISTs in Western and Asian countries, such as the clinical guidelines of GISTs published by the National Comprehensive Cancer Network (NCCN) in 2004 (5), and by the European Society of Medical Oncology (ESMO) in 2014 (6). However, excluding GISTs, for those other gastric SMTs, most of which are deemed benign, the necessity and timing of intervention has been ignored.

For reference, this paper will focus on the malignancy of gastric SMTs which are generally considered benign.

Heterotopic pancreas

Heterotopic pancreas is defined as pancreatic tissue abnormally situated, which is anatomically characterized by the separation of pancreatic tissue from glands, without neurological or vascular continuity (7). The most common site of gastrointestinal heterotopic pancreas is the stomach (25–62%), followed by the duodenum (25–35%), and jejunum (16%) (8). The clinical manifestations of heterotopic pancreas is asymptomatic or non-specific, such as epigastric pain, nausea, vomiting and so on. Therefore, it is usually detected by endoscopy examination or autopsy incidentally (9).

The malignant tumors of gastric heterotopic pancreas are comparatively rare but need to be alarmed. There were 1,724 cases reported in the literature, which were composed of newborn to 89 years old patients. The sex ratio (M/F) was about 0.9. The tumor size ranged from 0.4 to 12.5 cm. Of all the 1,724 cases reported from 1980 to 2018, we found 29 cases with malignant features (Table 1). For a carcinoma to be described as arising from heterotopic pancreatic tissue, three criteria have been proposed: (I) the tumor must be found within, or close to, the ectopic pancreatic tissue; (II) transition between pancreatic structures and carcinoma must be observed (i.e., duct-cell dysplasia and/or carcinoma in situ); (III) the non-neoplastic pancreatic tissue must include at least fully developed acini and duct structures. The lesion in this case met all three criteria (10). The 29 cases were confirmed pathologically originated from gastric heterotopic pancreas. Among the 29 malignant cases, most of them were adenocarcinoma (21/29), and other pathological types included papillary cystadenocarcinoma, mucinous cystadenocarcinoma, neuroendocrine carcinoma, acinar cell carcinoma and so on. Mean age of the cases was 58.4±15.6 [27–86] years old and the male to female ratio was 14/15. The tumor size ranged from 1.7 to 12.5 cm (Table 2).

Table 1

Information of reviewed gastric submucosal tumors

Histological diagnosis Reference No. Total case No. Gender (M/F) Age (Y) Size (cm) Malignant case No.
Heterotopic pancreas 291 1724 405/457 Newborn–89 0.4–12.5 29
Leiomyoma 133 946 80/85 16–86 0.5–21 16
Schwannoma 83 530 121/275 5–90 0.3–15 11
Glomus tumor 97 195 73/109 19–90 0.8–17 11
Hemangioendothelioma 5 5 3/2 21–71 4–7 2
Granular cell tumor 27 35 14/15 20–76 0.5–10.5 1
Lipoma 80 141 55/37 22–84 0.4–16 0
Hemangiopericytoma 1 1 0/1 56 0.8 0
Lymphangioma 11 11 4/6 16–68 1.5–22 0
Neurofibroma 13 13 9/4 14–62 1.1–9 0

Table 2

Details of malignant gastric submucosal tumors

Histological diagnosis Reference Age/gender Appearance Size (cm) Treatment Follow up
Heterotopic pancreas
   Adenocarcinoma Nakao et al. (11) [1980] 54/M Abdominal pain, weight loss Nd Surgery Deceased, 9 months after surgery
   Adenocarcinoma Nakao et al. (11) [1980] 28/F Epigastric pain Nd Nd Uneventful at 2 years
   Adenocarcinoma Hickman et al. (12) [1981] 58/M weight loss, periodic epigastric pain, vomiting 2.3 Subtotal gastrectomy Metastatic pancreatic adenocarcinoma, 7 years after surgery
   Papillary cystadenocarcinoma Mibayashi et al. (13) [1983] 44/F Epigastralgia Nd Subtotal gastrectomy Nd
   Adenocarcinoma Bedossa et al. (14) [1991] 42/M Gastric stasis Nd Gastrectomy Uneventful at 4-month follow-up
   Heterotopic pancreas with malignant transformation Jeng et al. (15) [1991] 27/F Epigastric fullness, heart-burn, nausea, acid regurgitation 2.5×2.0 Subtotal gastrectomy with radical lymph node resection Uneventful at 2-year
follow-up
   Adenocarcinoma Ura et al. (16) [1998] 60/F Asymptomatic 3×3.3 Proximal gastrectomy with regional lymph node dissection Nd
   Mucinous cystadenocarcinoma Cho et al. (17) [2000] 73/F Nd Nd Nd Nd
   Adenocarcinoma Osanai et al. (10) [2001] 57/F Epigastric discomfort and periodic nausea 12.5×9 Total gastrectomy Deceased, 13-mo follow-up
   Adenocarcinoma Halkic et al. (18) [2001] 60/M Epigastric pain, dysphagia, weight loss 6×4.5×4 Surgery Died 4 months following surgery
   Adenocarcinoma Jeong et al. (19) [2002] 64/M Dyspepsia, vomiting 3×3 Roux-en-Y esophagojejunostomy and a Braun anastomosis Uneventful at 1 year
   Adenocarcinoma Emerson et al. (20) [2004] 52/M Epigastric, left upper quadrant pain, emesis, and bloating 4×2.5 50% gastrectomy with vagotomy Uneventful 9 months after surgery
   Neuroendocrine carcinoma (grade I) Chetty et al. (21) [2004] 85/M Dyspepsia, increase in stool frequency 1.7 Distal gastrectomy Uneventful at 1 month
   Adenocarcinoma Eun et al. (22) [2004] 35/M Asymptomatic 2×1.7×1.2 Wedge resection Uneventful at 5 months
   Acinar cell carcinoma Sun et al. (23) [2004] 86/F Anemia 5×3×2 Partial gastrectomy with a Billroth-II reconstruction Nd
   Adenocarcinoma Matsuki et al. (24) [2005] 58/F Vomiting 2.5×1.7 Partial gastrectomy Uneventful, 1.5 years later
   Adenocarcinoma Yoshida et al. (25) [2007] 64/M Abdominal fullness Nd Gastrectomy Nd
   Acinar cell carcinoma Mizuno et al. (26) [2007] 73/M Epigastralgia 7.6×4.9 Pancreaticoduodenectomy Uneventful at 11 months
   Adenocarcinoma Kimura et al. (27) [2008] 31/F Epigastralgia 5×2 Distal gastrectomy Nd
   Adenocarcinoma Papaziogas et al. (28) [2008] 56/F Epigastric pain 2×1.2 Distal gastrectomy Uneventful at 6 months
   Adenocarcinoma Suk et al. (29) [2011] 69/F Vomiting 7×2 Gastrectomy Nd
   Adenocarcinoma Fukumori et al. (30) [2011] 76/F Nd Nd Gastrectomy on the pylorus side, lymph node dissection (D2), and cholecystectomy Nd
   Adenocarcinoma Okamoto et al. (31) [2012] 75/F Epigastralgia 4 Laparotomy Uneventful, 11-year follow-up
   Adenocarcinoma Endo et al. (32) [2014] 73/M Epigastric pain 4.5×3×2.5 Distal gastrectomy with regional lymph node dissection and cholecystectomy Lymph node metastasis at 2-year follow-up
   Adenocarcinoma Lemaire et al. (33) [2014] 60/M Dyspepsia and epigastric heaviness 7.5×4.4 Total gastrectomy with D2 lymphadenectomy Uneventful, 4-year follow-up
   Adenocarcinoma Priyathersini et al. (34) [2017] 45/M Early satiety, vomiting, constipation 5×4.3×3.5 A subtotal gastrectomy with anterior jejunostomy Uneventful at 12-month follow-up
   Acinar cell carcinoma Kim et al. (35) [2017] 54/M Incidental finding 2.7 Laparoscopic wedge resection Uneventful at 33-month follow-up
   Adenocarcinoma Wang et al. (36) [2017] 63/F Asymptomatic 2.4 Gastric wedge resection Uneventful at 8-month follow-up
   Neuroendocrine tumor (grade I) Tanaka et al. (37) [2018] 72/F Incidental finding 1.6×1.2×0.6 Laparoscopic and endoscopic cooperative surgery Nd
Leiomyoma
   Leiomyosarcoma Pauser et al. (38) [2008] 37/M Reflux 1 Resected endoscopically Uneventful, 3-year follow-up
   Leiomyosarcoma Masuzawa et al. (39) [2009] 29/F Upper abdominal pain and occasional black stool 11×9.7×3.2 Distal gastrectomy and regional lymphadenectomy Uneventful at 8-month follow-up
   Leiomyosarcoma Soufi et al. (40) [2009] 16/F Massive hematemesis and shock without epigastralgia Nd Subtotal gastrectomy Uneventful at 18-month follow-up
   Leiomyosarcoma Park et al. (41) [2011] 79/M Epigastric pain and gastric subepithelial tumor 4.6×4.2 Laparoscopic wedge resection Recurrent leiomyosarcoma with multiple liver metastases, 1-year follow-up
   Leiomyosarcoma Aggarwal et al. (42) [2012] 26/M Abdominal pain, black stools, and lightheadedness 7.2 Gastrectomy Lost to follow-up 1 month after surgery
   Leiomyosarcoma Damiano et al. (43) [2012] 71/M Anemia and melena 9 Atypical gastric resection Uneventful at 28-month follow-up
   Leiomyosarcoma Insabato et al. (44) [2012] 51/M Asthenia, weight loss, and slight sideropenic anemia 4×1.6 Total gastrectomy with Roux-en-Y esophagojejunal anastomosis Uneventful at 10-month follow-up
   Leiomyosarcoma Yamamoto et al. (45) [2013] 51/M Nd 2.5 Resected surgically Uneventful at 18-month follow-up
   Leiomyosarcoma Weledji et al. (46) [2014] 69/M Vomiting associated with upper abdominal bloatedness, epigastric pain 10×8×7 Billroth-II gastrectomy Nd
   Leiomyosarcoma Rou et al. (47) [2015] 48/F Abdominal discomfort and generalized weakness 2 Chemotherapy Died after 1 year due to tumor progression
   Leiomyosarcoma Tarchouli et al. (48) [2015] 32/F Painful mass of the left hypochondrium 21×14×12 Ne-piece resection with mass, spleen, large omentum and a flange of the gastric wall Died 2 years later in an array of pulmonary metastases
   Leiomyosarcoma Hasnaoui et al. (49) [2018] 63/F Hematemesis, melena and hemodynamic instability 9 Total gastrectomy Nd
   Leiomyosarcoma Kitagawa et al. (50) [2018] 64/M Abdominal mass and mild anemia 3 Partial gastrectomy Uneventful, 2-year follow-up
   Leiomyosarcoma Mehta et al. (51) [2018] 47/M Pain in the left hypogastric region 13×13×10 Laparotomy with total excision of the greater curvature of the stomach 2 years later, liver metastases, died 11 months after metastases
   Leiomyosarcoma Roh (52) [2018] 86/F Nd Nd Partial gastrectomy and chemotherapy, Y-90 therapy treated liver metastasis Liver metastasis
   Leiomyosarcoma Sato et al. (53) [2018] 74/F Asymptomatic 1.5 Endoscopic submucosal dissection (ESD) Uneventful at 36-month follow-up
Schwannoma
   Malignant schwannoma Petersen et al. (54) [1984] 42/M Upper gastrointestinal bleeding 2 Electrocautery under endoscopy Died 7 days later of gram-negative sepsis
   Malignant schwannoma Radulescu et al. (55) [1995] 27/F Epigastric pains accompanied by melena Nd* Nd Nd
   Malignant schwannoma Bees et al. (56) [1997] 10/F Poor appetite, fatigue, pallor, fainting and tarry stools 3 Billroth-I Nd
   Malignant schwannoma Loffeld et al. (57) [1998] 41/F Melaena 4 Gastrectomy Uneventful at 5 years
   Malignant schwannoma Watanabe et al. (58) [2011] 34/M Asymptomatic 1.9×1.8 Laparoscopy-assisted partial gastrectomy Uneventful at 2 years
   Malignant schwannoma Takemura et al. (59) [2012] 70/M Melena 6×5 Distal gastrectomy with regional lymph node dissection 3 months after surgery with liver metastases, died 5 months after surgery
   Malignant schwannoma Zheng et al. (60) [2014] 67/M Gastric pain 6.7 Surgery Died of unrelated causes, 80 months
   Malignant schwannoma Zheng et al. (60) [2014] 73/F Hematemesis, melena 5.2 Surgery Died of metastasis or recurrent of the primary disease, 15 months
   Malignant schwannoma Zheng et al. (60) [2014] 61/M Gastric pain 5.7 Surgery Uneventful at 28 months
   Malignant schwannoma Zheng et al. (60) [2014] 65/F Detected during CT for unknown symptoms 6.2 Surgery died of metastasis or recurrent of the primary disease, 15 months
   Malignant schwannoma Kim et al. (61) [2015] 48/M Melena 9 Subtotal gastrectomy with D1+ lymph node dissection and Billroth-II reconstruction Nd
Glomus tumor
   Malignant glomus tumor Folpe et al. (62) [2001] 69/M Nd 8.5 Surgery Liver metastasis, 3 years later
   Malignant glomus tumor Miettinen et al. (63) [2002] 69/M Nd 6.5×6×3 Surgery Died, 50 months, liver metastases
   Malignant glomus tumor Bray et al. (64) [2009] 58/M Nd 11×9×17 Surgery Cutaneous metastasis 6 years later
   Malignant glomus tumor Lee et al. (65) [2009] 65/F Epigastric pain and a loss of appetite 3 A wedge resection of the gastric mass Metastases in the kidney and brain, died of respiratory insufficiency 8 months later
   Malignant glomus tumor Lee et al. (65) [2009] 63/M Epigastric pain 9 Chemotherapy Died, extensive bleeding from the main tumor mass
   Malignant glomus tumor Hong et al. (66) [2010] 61/M Dizziness and tarry stool 4 Palliative wedge resection of the stomach Nd
   Malignant glomus tumor Teng et al. (67) [2012] 66/F Abdominal fullness 5.3×5×4.9 Subtotal gastrectomy Uneventful at 9-month follow-up
   Malignant glomus tumor Teng et al. (68) [2012] 43/F Melena 2.5 Endoscopic therapy Nd
   Malignant glomus tumor Akahoshi et al. (69) [2014] Nd Nd 1.2 Surgical local resection No recurrence
   Malignant glomus tumor Zaidi et al. (70) [2016] 53/F Fullness and pain in the left hypochondrium 10 Laparotomy and resection of the gastric mass Uneventful at 15-month follow-up
   Malignant glomus tumor Davis et al. (71) [2018] 46/F Incidental finding 1 Wedge excision of the stomach tumor Liver metastasis
Hemangioendothelioma
   Hemangioendothelioma Seki et al. (72) [1985] 21/F Melena 6 Laparoscopy Nd
   Epithelioid angiosarcoma Xia et al. (73) [2018] 56/M Melena and epigastric dull pain 7 Total gastrectomy with D2 lymph node dissection Liver and retroperitoneal lymph node metastasis 1 month later
   Granular cell tumor Matsumoto et al. (74) [1996] 64/F Epigastric discomfort after meals 5.5/7 Billroth-I Recurrence, 21 months after surgery. Uneventful, 6-month follow-up after last operation

*, Nd: no data.

In addition to malignant cases of heterotopic pancreas, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN) have also been found in heterotopic pancreas. In 1,724 cases, 47 PanINs/IPMNs were found. Based on the mathematical analysis by Yachida et al. (75), it takes about 12 years for PanIN-1 to transform into PanIN-3, which can cause pancreatic ductal adenocarcinomas. According to the study by Jun et al. (76), PanINs/IPMNs were more frequently found in heterotopic pancreas of large size, deep location and infiltrative growth pattern. And most PanINs/IPMNs associated with heterotopic pancreas were low-grade, so progression to ductal adenocarcinoma during a short follow-up period is unlikely.

Therefore, although the malignant cases are rare in gastric heterotopic pancreas, we also need to be cautious when we find gastric heterotopic pancreas.

Leiomyoma

Leiomyoma is the most common SMT of upper gastrointestinal tract (77). Until the 1980s, GIST was not significantly different from a leiomyoma. It was not until 1983 when Mazur and Clark (78) proposed the concept of stromal tumors that their differences were gradually noticed. And in 1998, Hirota et al. (79) confirmed the pathogenic effect of Kit (CD117) proto-oncogene activating mutation on GISTs. Subsequently, GISTs were confirmed to have the characteristics of Cajal interstitial cells, which more specifically differ leiomyoma from GIST. So in order to get more reliable data, we only searched literatures between 2008–2018.

From 2008 to 2018, we reviewed 133 literatures and found 946 cases of gastric leiomyoma reported. Of the 946 cases, 16 were leiomyosarcomas. The clinical manifestations of these malignant tumors were not specific, such as epigastric pain, melena, gastric outlet obstruction and so on. The average age of these 16 cases was 52.7±20.7 [16–86] years old. The male to female ratio was 9/7. The average size of tumors was 7.06±5.60 [1–21] cm. The literature indicates that gastric leiomyosarcomas often occurs in the elderly and are typically of high grade malignancy (38). However, our review showed that some middle-aged and even young patients also suffer from this disease. And the tumor size was also extensively ranged. So neither age nor tumor size can be used as criteria for judging malignant potential. Some leiomyosarcomas had distant metastases at initial diagnosed. And liver and lungs were the most common sites.

Schwannoma

Schwannomas of the GI tract, firstly presented by Daimaru et al. in 1988 (80), which are mostly benign tumors arising from the schwann cells of the nerve sheath. The most common site (60–70% of all GI cases) is the stomach, followed by the colon and rectum (3%). Small intestinal and esophageal schwannomas are rarely reported (81).

Malignant gastric schwannomas are extremely rare, with only a few cases reported (Table 1). Of all the 530 cases reviewed, 11 showed malignancy (Table 2). Based on these conditions, we may conclude that malignant gastric schwannoma has atypical appearance with common gastrointestinal symptoms. Among these cases, there were 6 males and 5 females. The mean age of these cases was 48.9±20.2 [10–73] years old and the mean size of tumors was 4.97±2.25 [1.9–9] cm. Although the data of all the 530 cases showed a female predominance, the sex ratio of malignant schwannoma was close to 1:1, even male patients accounted for the majority. So we speculate that the possibility of malignancy is more likely to occur in males. With the increase of malignant cases, gender preference may decrease, and we can more intuitively analyze the characteristics of malignant schwannoma.

Vascular tumor

Vascular tumors, including angiogenic tumors and lymphangiomas, are relatively rare. Angiogenic tumors include glomus tumor, hemangioendothelioma, hemangiopericytoma and so on.

Glomus tumor, which is composed of modified smooth muscle cells (82), is an arteriovenous anastomosis functioning without an intermediary capillary bed (83). Most glomus tumors are benign neoplasms that occur in the dermis or subcutis of the extremities (84). Glomus tumors of stomach are relatively rare and often lead to gastrointestinal bleeding due to ulceration of the mucosa over which it is covered (85). We reviewed 97 articles and 195 cases from 1980 to 2018. According to the literature, the ages ranged from 19 to 90. Pathologically confirmed malignancy was found in 11 cases, and potential malignancy was uncertain in 3 cases. The others were benign. Folpe et al. (62) suggested malignant criteria of glomus tumors: tumors with a deep location and a size of more than 2 cm, or atypical mitotic figures, or moderate to high nuclear grade and ≥5 mitotic figures/50 HPF. All these 11 tumor cases met the above criteria. Of the 10 cases, 5 were male and 5 were female. The gender of the remaining 1 patient was not mentioned. The average age was 59.3±9.2 [43–69] years and the average tumor size was 6.18±4.75 [1–17] cm. As mentioned above, we can conclude that malignant cases usually occur in elderly patients and the risk of distant metastases cannot be ignored. And there seems to be no correlation between tumor size and malignant potential. The clinical manifestations of malignant tumors are mostly gastrointestinal symptoms without specificity. Although malignancy is rare in glomus tumors, we still need to pay close attention to it. What’s more, due to the risk of distant metastasis, long-term follow-up is necessary.

Hemangioendotheliomas which affects various parts of the digestive system (86) is classified into four types: Epithelioid hemangioendothelioma, spindle cell hemangioendothelioma, kaposiform hemangioendothelioma and endovascular papillary hemangioendothelioma (malignant tumor known as Dabska) (87). Gastric hemangioendotheliomas were rarely reported, only 5 cases, 2 of which were malignant tumors (Table 2). The tumor size of these 2 cases was relatively large. However, due to the limited number of cases, we cannot summarize the reliable common features of their malignancies.

Hemangiopericytoma of the stomach is even rarer and we found only one benign case of gastric lipomatous hemangiopericytoma. Lipomatous hemangiopericytoma is a variant of hemangiopericytoma, which is histologically composed of benign hemangiopericytomatous and mature lipomatous components (88). This was the first case of lipomatous hemangiopericytoma that occurred in the stomach, and more data is needed to deduce the possibility of malignancy.

Lymphangiomas are relatively rare compared with hemangiomas. And the digestive tract is rarely involved (89). We found 11 cases of gastric lymphangiomas, none of which were malignant.

Granular cell tumor (GCT)

GCT, first described by Abrikosoff in 1926 (90), is a benign mesenchymal tumor originating from schwann cell (91). GCTs most commonly affect the tongue, skin and subcutaneous tissue. And, 5% to 11% of GCTs are found in the gastrointestinal tract, and they mostly affect the esophagus, colon, or stomach (92). According to Fanburg-smith, there are six histologic criteria: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses/10 high-power fields at 200× magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign (93).

From January 1st, 1980 to December 31st, 2018, we found 36 cases of gastric GCTs (Table 1). Some of these gastric GCTs may coexist with gastric carcinoma and early gastric cancer. However, the pathology of these GCTs was confirmed benign. There was only one case of malignant gastric GCT, which was reported in 1996 by Matsumoto et al. A 64-year-old female was referred to the hospital for treatment due to upper abdominal discomfort after eating and gastroscopic evidence of enlargement of a SMT which had been managed conservatively by the hospital since 5 years ago. This neoplasm consisted of two tumor masses, 5.5 and 7.0 cm in diameter, respectively, which were connected to form a dumbbell-shaped lesion. After distal partial gastrectomy, reconstruction was performed by Billroth-I Method. The pathology of this case met the following criteria mentioned above: increased mitotic activity and pleomorphism. Although it only met two of the criteria, 21 months after the operation, the tumor recurred along the inferior border of the liver, 10.5 cm × 7.5 cm × 7.5 cm. Pathological characteristics of the tumor were similar to those of the primary tumor. Thus, considering the clinical and pathological evidence of local recurrence, the neoplasm was considered malignant (74).

Lipoma

Gastric lipomas account for less than 1% of gastric tumors and 5% of gastrointestinal lipomas (94). Lipomas are completely benign, although there is a risk of local recurrence, less than 5% (95). Of the 141 cases reviewed, no malignancy was reported (Table 1).

Neurofibroma

Neurofibroma often occurs in neurofibromatosis and solitary neurofibromas are rare (96). Neurofibromatosis type 1 is more common, frequently involving gastrointestinal tract (97). We reviewed 13 cases of gastric neurofibroma and none of them had malignant features. However, the clinical manifestations of neurofibromatosis are various, ranging from localized microscopic proliferative lesions of autonomic nerves and interstitial cells of Cajal and diffuse microscopic ganglio/neuro/fibromatosis to grossly recognizable mass-forming neurofibromas and GIST (98). Therefore, when gastric neurofibroma is diagnosed, neurofibromatosis needs to be considered and be alert.

Conclusions

We reviewed literatures and analyzed cases of gastric SMTs including GCT, lipoma, schwannoma, heterotopic pancreas, leiomyoma, vascular tumor (glomus tumor, hemangioendothelioma, hemangiopericytoma, lymphangioma) and neurofibroma. In this literature, there are cases of malignancy among GCT, schwannoma, heterotopic pancreas, leiomyoma, glomus tumor and hemangioendothelioma. It suggests that although most of these gastric SMTs are considered benign, there are still possibilities of malignancy, which requires our attention, even active intervention and long-term follow-up.

Acknowledgments

Funding: Zhejiang Provincial Natural Science Foundation of China, LY17H160022.

Footnote

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.10.41). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Yang B, Lu X. The malignancy among gastric submucosal tumor. Transl Cancer Res 2019;8(7):2654-2666. doi: 10.21037/tcr.2019.10.41

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