Schwannoma: A Rare Case of Submucosal Gastric Tumor

Schwannoma is a tumor that originates from the Schwann cells that surround a neuron’s axon. This tumor is very rare in the gastrointestinal tract and develops submucosally from intestinal nerve plexuses. The most common location for gastrointestinal schwannomas is the stomach, where they account for only 0.2% of gastric tumors. We present the case of a 56-year-old asymptomatic patient who was diagnosed, following a routine ultrasound examination, with an abdominal tumor. An abdominal MRI confirmed the gastric origin of the tumor. Although a subsequent upper-digestive endoscopic ultrasound was performed, a definitive diagnosis could not be established. Thus, a laparoscopic wedge resection of the stomach was performed. The immunohistochemical examination of the tumor established the diagnosis of benign schwannoma. Despite the availability of advanced endoscopy and imaging techniques, the diagnosis of gastric schwannoma is very rarely preoperative. The immunohistochemical identification of S-100 on the surgical specimen confirmed the diagnosis.

. Abdominal ultrasound showing the presence of an iso-hypoechoic tumoral formation, marked with a white arrow, in a 56-year-old patient without any abdominal symptoms. The stomach is indicated with a black arrow and the left hepatic lobe is marked LSH. The dimensions of the tumor in cm are specified at the bottom left. No other pathological changes were identified by ultrasound. Submucosal tumors, also known as mesenchymal tumors, are a group of tumors that contain spindle-shaped cells [1]. They are classified histopathologically as a gastrointestinal stromal tumor (GIST), tumors originating from smooth muscle tissue, which, in turn, includes leiomyomas, leiomyosarcomas, and tumors originating from nervous tissue. The latter category includes schwannomas, granular cell tumors, and neurofibromas [2]. Gastric schwannoma is a tumor that originates from the nerve plexus of the intestinal wall [3]. More specifically, this tumor originates from Schwann cell sheaths and represents 0.2% of all gastric tumors [4]. Most commonly, gastric schwan- Submucosal tumors, also known as mesenchymal tumors, are a group of tumors that contain spindleshaped cells [1]. They are classified histopathologically as a gastrointestinal stromal tumor (GIST), tumors originating from smooth muscle tissue, which, in turn, includes leiomyomas, leiomyosarcomas, and tumors originating from nervous tissue. The latter category includes schwannomas, granular cell tumors, and neurofibromas [2]. Gastric schwannoma is a tumor that originates from the nerve plexus of the intestinal wall [3]. More specifically, this tumor originates from Schwann cell sheaths and represents 0.2% of all gastric tumors [4]. Most commonly, gastric schwannoma originates from the Auerbach plexus, located in the smooth muscle layer of the gastric wall, and less commonly from the Meissner submucosal plexus. As it grows, the tumor pushes the nerve to the periphery, with no change in neuronal function [5]. This tumor is most often benign and is more common in women between the ages of 50-60 [4,6]. We present the case of a 56-year-old asymptomatic patient who was diagnosed, following a routine ultrasound examination, with an abdominal tumor. The ultrasound appearance of the tumor is presented in Figure 1.  Figure 3. Intraoperative image. The well-delimited tumor that developed from the anterior stomach wall is marked with a black arrow, and the stomach is spread with the help of the two grasping forceps, marked with a white arrow. Based on the description of the MRI, there was a suspicion that the identified tumor was a gastrointestinal stromal tumor (GIST) and thus an upper-digestive endoscopy was recommended. The endoscopy was carried out shortly after and showed that the tumor was located in the submucosal layer of the lesser curvature of the stomach. The echo-endoscopy examination revealed the tumor's hypoechoic appearance and origin from the muscle layer without causing disruption to the parietal stratigraphy. Two small tissue fragments were taken for histopathologic analysis and were described as having elongated nuclei, reduced nuclear pleomorphism, and an eosinophilic cytoplasm that may correspond to a mesenchymal type of tumor proliferation. However, an immunohistochemical determination of CD 117, CD34, desmin, actin, and S-100 was necessary to confirm the results. Due to the small size of the tissue collected through eco-endoscopic guidance, immunohistochemical examination could not be performed and the patient was admitted to the surgery clinic for a wedge gastrectomy. Endoscopic resection was excluded because the tumor size exceeded 3 cm. Thus, laparoscopic surgery was performed and a 5/5 cm encapsulated gastric tumor was discovered, originating from the anterior gastric wall near the lesser curvature; no other pathological findings of the intra-abdominal organs were detected. A partial resection of the anterior gastric wall was performed using an Endo-GIA purple stapler. The intraoperative perspective can be seen in Figure 3. The well-delimited tumor that developed from the anterior stomach wall is marked with a black arrow, and the stomach is spread with the help of the two grasping forceps, marked with a white arrow. Based on the description of the MRI, there was a suspicion that the identified tumor was a gastrointestinal stromal tumor (GIST) and thus an upper-digestive endoscopy was recommended. The endoscopy was carried out shortly after and showed that the tumor was located in the submucosal layer of the lesser curvature of the stomach. The echoendoscopy examination revealed the tumor's hypoechoic appearance and origin from the muscle layer without causing disruption to the parietal stratigraphy. Two small tissue fragments were taken for histopathologic analysis and were described as having elongated nuclei, reduced nuclear pleomorphism, and an eosinophilic cytoplasm that may correspond to a mesenchymal type of tumor proliferation. However, an immunohistochemical determination of CD 117, CD34, desmin, actin, and S-100 was necessary to confirm the results. Due to the small size of the tissue collected through ecoendoscopic guidance, immunohistochemical examination could not be performed and the patient was admitted to the surgery clinic for a wedge gastrectomy. Endoscopic resection was excluded because the tumor size exceeded 3 cm. Thus, laparoscopic surgery was performed and a 5/5 cm encapsulated gastric tumor was discovered, originating from the anterior gastric wall near the lesser curvature; no other pathological findings of the intra-abdominal organs were detected. A partial resection of the anterior gastric wall was performed using an Endo-GIA purple stapler. The intraoperative perspective can be seen in Figure 3. Microscopically, in hematoxylin-eosin staining, a well-delimited nodular tumor proliferation is detected and develops at the level of the gastric muscle proper. This tumor consist of monomorphic fusiform cells with an eosinophilic cytoplasm and elongated nuclei, with no mitotic activity identified, and with no intratumoral necrosis (Figure 5a,b). Thus, the exact type of tumor is determined by the immunohistochemical determination of CD117, CD 34, SMA-smooth muscle actin, and desmin-which are negative in this case. CD 117 is a marker that is present in gastrointestinal stromal tumors (GIST) and is expressed by the c-kit tyrosine kinase receptor and Cajal cells in the intestine [7].  (Figure 5a,b). Thus, the exact type of tumor is determined by the immunohistochemical determination of CD117, CD 34, SMA-smooth muscle actin, and desmin-which are negative in this case. CD 117 is a marker that is present in gastrointestinal stromal tumors (GIST) and is expressed by the c-kit tyrosine kinase receptor and Cajal cells in the intestine [7].     (Figure 6a,b). The absence of tumor expression of SMA-smooth muscle actin and desmin-obliges us to eliminate the diagnosis of leiomyoma (Figure 7a,b). The strong expression of S-100, a protein that is normally found only in Schwann cells originating from the neural crest, allows us to establish the diagnosis of schwannoma (Figure 8a). Vimentin is also diffusely positive in the tumor (Figure 8b). The glial fibrillary acidic protein (GFAP), which indicates an origin from the myenteric plexus, is positively zonal in tumor growth (Figure 8c). Thus, the diagnosis of gastric schwannoma is established without a doubt. Gastric schwannoma has a slow growth rate, and patients are often asymptomatic or have non-characteristic manifestations such as epigastric pain, episodes of upper-digestive bleeding, and even weight loss in 10-25% of cases [2]. The most common location for gastrointestinal schwannomas is the stomach [8]. Most gastric schwannomas are located in the body of the stomach, followed by the antrum, and the gastric fundus is the least common [4]. However, tumor positioning at small gastric curvatures seems to be the most common [9]. Among the useful paraclinical investigation methods in the diagnosis of gastric schwannoma, upper-digestive endoscopy is the first choice. The most frequently seen endoscopic image is a submucosal protuberance with normal mucosal cover. However, in one-quarter to one-half of the cases, we find central mucosal ulceration [10]. Although most cases of schwannoma are benign tumors, there are several cases of malignant schwannomas that have been reported [9]. This malignant character cannot be established clinically or through imaging examinations, although some authors argue that FDG (18F-fluorodeoxyglucose) PET-CT examination can distinguish between malignant cases that exhibit increased FDG uptake [9,11]. The presence of adjacent lymphadenopathies could also raise the suspicion of malignancy [12]. However, increased FDG uptake has also been observed in benign schwannomas, which could be explained by the role of Schwann cells in glucose transport being necessary for axonal repolarization [13]. No correlation has been  (Figure 6a,b). The absence of tumor expression of SMAsmooth muscle actin and desmin-obliges us to eliminate the diagnosis of leiomyoma (Figure 7a,b). The strong expression of S-100, a protein that is normally found only in Schwann cells originating from the neural crest, allows us to establish the diagnosis of schwannoma (Figure 8a). Vimentin is also diffusely positive in the tumor (Figure 8b). The glial fibrillary acidic protein (GFAP), which indicates an origin from the myenteric plexus, is positively zonal in tumor growth (Figure 8c). Thus, the diagnosis of gastric schwannoma is established without a doubt. Gastric schwannoma has a slow growth rate, and patients are often asymptomatic or have non-characteristic manifestations such as epigastric pain, episodes of upper-digestive bleeding, and even weight loss in 10-25% of cases [2]. The most common location for gastrointestinal schwannomas is the stomach [8]. Most gastric schwannomas are located in the body of the stomach, followed by the antrum, and the gastric fundus is the least common [4]. However, tumor positioning at small gastric curvatures seems to be the most common [9]. Among the useful paraclinical investigation methods in the diagnosis of gastric schwannoma, upper-digestive endoscopy is the first choice. The most frequently seen endoscopic image is a submucosal protuberance with normal mucosal cover. However, in one-quarter to one-half of the cases, we find central mucosal ulceration [10]. Although most cases of schwannoma are benign tumors, there are several cases of malignant schwannomas that have been reported [9]. This malignant character cannot be established clinically or through imaging examinations, although some authors argue that FDG (18F-fluorodeoxyglucose) PET-CT examination can distinguish between malignant cases that exhibit increased FDG uptake [9,11]. The presence of adjacent lymphadenopathies could also raise the suspicion of malignancy [12]. However, increased FDG uptake has also been observed in benign schwannomas, which could be explained by the role of Schwann cells in glucose transport being necessary for axonal repolarization [13]. No correlation has been found between tumor size, ki-67 index, and FDG uptake rate, making histopathological examination essential for both establishing the diagnosis method of schwannoma and for characterizing it as benign or malignant [13]. Although there are no certain indicators of the malignancy of digestive schwannomas, a MIB-1 ki-67 proliferative index higher than 10% and a mitotic activity rate above 5 HPF, along with nuclear atypia and tumor dimensions over 5 cm, are associated with an increased risk of malignancy [6]. There are even cases described in the literature where patients developed secondary liver determinations, leading to death [9]. In the case presented, it is clear that we are faced with benign schwannoma, as no mitotic activity was identified, and the ki-67 is 2%. Most often, schwannomas are confused with GISTs due to their submucosal location and well-defined, encapsulated appearance [3]. Immunohistochemical examination shows a strong expression of S-100 in schwannomas compared to GISTs, which are positive for CD-34, c-kit, and DOG 1 or leiomyoma, which is positive for desmin and smooth muscle actin (SMA) [2,14]. Immunohistochemical positivity for glial fibrillary acidic protein (GFAP) indicates an origin from the enteric plexus; thus, these tumors can be considered to be different to peripheral schwannomas [8]. The removal of submucosal gastrointestinal tumors is recommended when the tumor size is over 2 cm. Tumors below this size have an indication for endoscopic monitoring [15]. The endoscopic removal of the tumor is recommended for tumors under 3 cm and can be performed through endoscopic submucosal excavation (ESE), endoscopic full-thickness resection (EFTR), and submucosal tunneling endoscopic resection [15,16]. Endoscopic removal of gastric schwannoma has also been found to be useful and safe, with good long-term results. Tumors as large as 55 mm have been removed endoscopically [16]. The surgical removal of schwannoma, either through a classical or laparoscopic approach, with gastric resection or limited but complete excision of the tumor, is associated with good long-term results without significant recurrence rates [17]. However, some authors have observed the concurrent presence of malignant diseases such as gastric cancer, colon cancer, renal cancer, non-Hodgkin's lymphoma, GIST, breast cancer, pancreatic cancer, and lung cancer. In 50% of cases, the cancer diagnosis was made before the discovery of the schwannoma, in 40% it was made concurrently, and in only one case it was made after the discovery of the benign tumor [6]. In conclusion, the diagnosis of gastric schwannoma is very rarely established preoperatively, despite the advanced diagnostic arsenal offered by echo-endoscopy, CT, or PET [5]. The removal of the tumor through endoscopic or surgical procedures, adapted to each case, allows for the accurate establishment of the diagnosis.
Funding: This research received no external funding.
Institutional Review Board Statement: Ethical review and approval were waived for this study due to it being a retrospective case report, which did not impact the management of the patient.

Informed Consent Statement:
Written informed consent has been obtained from the patient to publish this paper.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.

Conflicts of Interest:
The authors declare no conflict of interest.