Gastric Schwannoma—Two Unusual Cases with Usual Presentation and Review of Literature

Abstract

Schwannomas, also known as neurilemmomas, are characteristically benign, slow growing neoplasms originating from Schwann cell sheath. Gastrointestinal schwannomas are very rare with stomach being the most affected organ representing approximately 0.2% of all gastric tumours. Malignant transformation is rarely reported in these tumors and complete surgical resection with negative margins is the recommended treatment. Herein, we report our experience of 2 cases of gastric submucosal spindle cell tumour (SMT), which were preoperatively assumed to be as gastrointestinal stromal tumor (GIST), however postoperatively confirmed as schwannoma on immunohistochemical examination.

Introduction

World Health Organization (WHO) classified gastric tumours into 2 types- epithelial neoplasms and non-epithelial neoplasms. Epithelial neoplasms arise from mucosa, whereas non-epithelial neoplasms, also called as mesenchymal tumours of gastric wall or SMTs, originate from submucosa, muscularis propria or serosa [1]. These SMTs are spindle cell tumours which include GIST, leiomyoma, leiomyosarcoma and schwannoma. Amongst these, GIST is the most common primary mesenchymal tumour of the stomach [2]. Schwannoma is usually benign and commonly encountered in head and neck region with vestibular schwannomas being the most common variant. The gastrointestinal tract is a rare site for schwannoma and stomach is the most-commonly affected site in gastrointestinal tract. Gastric schwannoma represent 0.2 % of all gastric tumours [3].

Case 1

Thirty-nine years old lady presented with upper abdominal pain for 1 month. On evaluation, endoscopy revealed a polypoidal lesion with central umbilication in stomach. Endoscopic biopsy was suggestive of hyperplastic polyp. Contrast enhanced computerised tomography (CECT) scan demonstrated 4.6 × 4.3 × 3.8 centimetre (cm), well-defined lobulated lesion arising from greater curvature in mid-body region of stomach with homogenous post-contrast enhancement and no significant areas of necrosis along with few sub-cm peri-gastric lymph nodes (Fig. 1). Considering the size and symptomatic presentation of the lesion, patient was counselled for surgery. Patient underwent distal gastrectomy with D1 lymphadenectomy with Roux-en-Y gastrojejunostomy with jejunojejunostomy. Postoperative recovery was smooth and uneventful. Histopathology revealed spindle cell tumour involving gastric lamina propria, submucosa, muscle coat and serosa with extremely sparse mitotic activity without necrosis with no metastasis in 14 resected peri gastric lymph nodes. Proximal and distal resection margins were unremarkable (R0 resection). Immunohistochemistry (IHC) showed diffuse expression of S-100 protein, SOX-10, patchy expression of CD-34 and immune-negative for c-kit, DOG-1, NTRK, confirming the diagnosis of Gastric schwannoma (Fig. 2). Patient was kept on observation with 4 monthly follow up. On 1 year follow-up, patient is doing well with no evidence of recurrence.

Fig. 1.

(A) CECT Scan showing well defined mass in relation to greater curvature of stomach with homogenous post-contrast enhancement. (B) Endoscopy image showing submucosal lesion with central umbilication. (C) Intra-operative image showing lesion on the body of stomach along greater curvature

Fig. 2.

Electron microscopy and IHC findings of gastric schwannoma. (A) Spindle shaped tumor cells arranged in short fascicles and cords with elongated nuclei. (B) Diffuse expression of $100 immunostain in tumour cells. (C) Diffuse expression of SOX-10 in tumour cells. (D) Absence of CD117staining in tumour cells

Case 2

Sixty-year-old hypertensive lady presented with upper abdominal pain, vomiting, loss of appetite for 15 days. Endoscopy revealed large submucosal mass in distal body of stomach near incisura on lesser curvature. Endoscopic biopsy was inconclusive. CECT scan was suggestive of large, well-defined soft tissue mass in distal stomach arising from lesser curvature suggestive of GIST with few sub-cm sized enlarged peri-gastric lymph nodes. Since the patient had gastric outlet obstruction due to large mass and radiological findings of GIST, she was counselled for surgery regardless of inconclusive biopsy. She underwent subtotal gastrectomy with D1 lymphadenectomy with Roux-en-Y gastrojejunostomy with jejunojejunostomy. Intraoperative course was smooth and uneventful. Histopathology revealed gastric spindle cell tumour with spindle cells arranged in short fascicles, uninvolved mucosa, inconspicuous mitotic activity, resection margins free and no metastasis in 11 resected peri-gastric lymph nodes. IHC confirmed diagnosis of gastric schwannoma with expression of S-100 protein and immune-negative for CD-34, C-KIT, DOG-1, Smooth Muscle Actin and desmin. She was advised regular follow up. At 2-year follow-up, patient is doing well without any recurrence.

Discussion

Gastric schwannomas (GS) are unusually encountered gastric tumors and they fall under gastrointestinal SMT category. SMTs are generally classified into three groups: myogenic (leiomyomas or leiomyosarcomas), neurogenic (schwannomas, granular cell tumours, and neurofibromas) and GISTs. Of these, GIST is the most common gastrointestinal SMT. Leiomyomas and schwannomas are usually benign tumours, GISTs are considered potentially malignant and leiomyosarcomas are considered malignant [4]. Schwannomas account for 91% of the tumours in the neurogenic group and the most frequent locations are stomach (60–70%), colon and rectum. The small intestine and oesophagus are the less commonly affected sites. GS are almost uniformly benign without nodal or distant metastasis [5]. GS represents 5% of nonepithelial gastric tumour [6]. Table 1 elaborates the key clinico-radiological and pathological features of different SMTs.

Table 1.

Clinico-radiological and pathologic features of various gastric SMTs

	Schwannoma	Leiomyoma	GIST
Age	40-50 years	50-70 years	60-65 years
Gender	Female >Male	Male =Female	Male >Female
Site	Lesser curvature >body >antrum >fundus	Cardia >GE junction	Greater curvature
Radiological Features (CECT Scan)	Hypodense, well- demarcated lesion with homogenous enhancement. Exophytic or mixed growth pattern. No haemorrhage, necrosis, cystic change or calcification.	Homogenous hypodense lesion with mild-moderate contrast enhancement. Endoluminal growth pattern.	Large, hyper-vascular lesions with heterogenous contrast enhancement. Predominantly exophytic growth pattern. Haemorrhage, necrosis and cystic change.
Histopathology	Encapsulated tumours consisting of spindle cells with prominent lymphoid aggregations. Antoni-A, Antoni-B areas Absence of typical Verocay bodies.	Spindle cells with eosinophilic cytoplasm	Cellular morphology ranges from spindle shaped to epitheloid in character. 70% spindle- cell type, 20% epitheloid cell type, 10%-mixed type.
IHC	Positive for S100, GFAP, Vimentin, Calretinin, SOX-10, PGP9.5	Positive for Desmin, SMA	Positive for CD-117, CD-34, Actin
Malignant Transformation	Extremely rare	Extremely rare	20-30%
Treatment	Surgery	Surgery	Surgery + TKI

GIST: gastrointestinal stromal tumor, CECT: contrast enhanced computed tomography, IHC: immunohistochemistry, TKI: Tyrosine kinase inhibitor

GSs are usually solitary lesions arising from the lesser curvature of the stomach, most commonly on gastric body (50%), followed by gastric antrum (32%) and fundus (18%). Most of GSs are incidentally detected. (4). GSs tend to present in the 5–6^th decade of life with slight female predominance. GS typically lack noticeable features and are often found incidentally. While often asymptomatic, GS can cause abdominal discomfort, palpable mass, and sometimes gastroduodenal intussusception. Gastrointestinal bleeding may occur when growing mass compresses the mucosa, causing ischaemia and ulceration [7]. Endoscopy usually reveals a submucosal elevated lesion with a smooth overlying mucosa; a central ulcer can be seen in 25–50% of cases due to ischemic changes in the covering mucosa (4). Endoscopic ultrasound (EUS) can help to differentiate between GS and GIST. In comparison to GIST, GS appears to be a low-density lesion with a clear boundary compared with the surrounding muscularis propria. It appears as uneven hypoechoic lesion, with most of it originating from the muscularis propria [8]. EUS features can help to differentiate various mesenchymal neoplasms, however, accurate subclassification can only be done with further tissue acquisition for IHC. Researchers have studied the diagnostic accuracy of EUS with tissue sampling and subclassification of gastrointestinal SMTs and reported accuracy of 61.7% with EUS guided Trucut biopsy [9]. GS usually shows a well-defined, oval, and iso- to mildly hypo-attenuated mass compared with the liver on plain CT images, and a homogenous enhancement pattern on enhanced CT images. These tumours mostly represent as exophytic masses or mixed growth pattern. However, cystic change, cavity formation, necrosis, haemorrhage or calcification are uncommon [10].

Histologically GSs are spindle cell neoplasms that typically have two components: compact spindle cell components (Antoni A areas), showing occasional palisading (Verocay Bodies) alternating with hypocellular areas (Antoni B areas). Focal nuclear atypia and mitotic activity may be present. IHC is usually must to confirm the diagnosis and differentiate it from other SMTs. On IHC, these tumour cells are strongly and uniformly positive for S100 protein and usually positive for glial fibrillary acid protein (GFAP); EMA positivity may be encountered in subcapsular areas. GSs are negative for CD117, DOG1, CD34, SMA, and desmin, and hence can be easily distinguished from GISTs which are positive for CD117 and DOG-1 or from leiomyoma which are positive for SMA and desmin [4]. Mutational analysis is also helpful to differentiate schwannomas from GIST. GIST is known to have specific mutations in the c-KIT and PDGFRA genes while schwannomas do not, however GSs rarely exhibit somatic NF2 mutations, which are more commonly encountered in soft tissue schwannomas [2].

GSs are associated with good prognosis with extremely rare possibility of malignant transformation (10). Incidence of lymph nodal metastasis in GS is rare. Literature has reported advanced malignant GSs with liver metastasis, but not to the lymph nodes. In contrast to GIST, tumour size and mitotic rate do not have prognostic significance in GS. Tumour recurrence is generally preceded by an incomplete surgical resection. Complete surgical resection with negative margins is the mainstay of treatment without any other adjuvant therapy. Studies exploring the utility of frozen section in establishing the diagnosis of SMTs have not been very promising as IHC is required for classifying definitive subtype of SMTs [11]. The surgical approach depends on the tumour size, localization, surgeon experience and preference [6, 7]. Since chemotherapy and radiotherapy are usually ineffective, surgery is the definitive treatment in malignant GSs [7].

Conclusion

GS is an important differential diagnosis of sub-mucosal tumours of stomach. Pre-operative diagnosis of GS can be difficult on endoscopic and imaging modalities and only IHC can reliably differentiate GS from GIST. Upfront surgical resection remains the treatment of choice for GS.

Declarations

Conflict of Interest

The authors declare no competing interests.