Gastric granular cell tumour, a rare entity

Abstract

Granular cell tumours are rare neoplasms that may occur anywhere in the body. The most common locations are the oral cavity, skin and subcutaneous tissue, with only 8% of these tumours occurring at a gastrointestinal site. In the specific case of gastric granular cell tumours, only a few cases have been published until today. Granular cell tumours are usually benign; however, some malignant forms have been reported. Both endoscopic and surgical resection represent the treatment of choice. The authors report a new clinical case of a gastric granular cell tumour, treated with laparoscopic surgical resection, describing some endoscopic, imagiological and anatomopathological features.

Background

Granular cell tumours (GCTs) were first described by Abrikossoff in 1926. They are rare, usually benign, neoplasms that may occur at many sites, with only 8% of the cases occurring at a gastrointestinal location.¹ Most of the gastrointestinal GCTs are located in the oesophagus and large bowel, but rarely in the stomach.²

According to Patti et al,¹ up until 2006 only 29 cases of GCTs with a gastric location were reported. Since 2006, 21 more cases have been described.^2–7

In this paper, the authors report a case of a 52-year-old woman with a gastric GCT treated with laparoscopic surgical resection, describing some endoscopic, imagiological and anatomopathological features.

Case presentation

A 52-year-old woman was evaluated in a general surgery appointment, for the investigation of a lesser curvature submucosal gastric tumour. The diagnosis had been made by an upper endoscopy performed routinely for dyspeptic symptoms.

The upper endoscopy reported a submucous polypoid lesion at the angular incisure, covered with normal mucosa and with a hard consistency (figure 1).

Figure 1.

Upper endoscopy showing a hard, submucous, polypoid lesion covered with normal mucosa (arrow).

The lesion was biopsied; however, the biopsy was inconclusive.

Investigations

Laboratory studies did not show any abnormalities. Complete blood count, coagulation studies, renal function and tumoural markers, such as chromogranin A, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), were all within the normal range.

Endoscopic ultrasonography (EUS) revealed a subepithelial, heterogenic and hypoechoic lesion, 19 mm large, with origin in the third or fourth stomach layer at angular incisure. No perilesional, mediastinal or celiac region adenopathies were identified (figure 2).

Figure 2.

Endoscopic ultrasonography that revealed a subepithelial, heterogenic and hypoechoic lesion, 19 mm large, with origin in the third or fourth stomach layer (arrows).

A guided biopsy was performed, but it was again inconclusive.

Abdominopelvic CT showed an area of nodular thickening involving the posterior wall of the prepyloric antrum, mimicking the existence of a submucous lesion of approximately 20 mm. No extraparietal abnormalities were seen and the perigastric adipose tissue was intact (figure 3).

Figure 3.

CT (axial and coronal sections) with a nodular thickening involving the posterior wall of the prepyloric antrum, of approximately 20 mm, mimicking the existence of a submucous lesion (arrows).

Magnetic resonance of the superior abdomen revealed a nodular, slightly hypervascular and intraparietal lesion of 21 mm, in the gastric small curvature. The radiologist considered that the lesion could correspond to a gastrointestinal stromal tumour (GIST) (figure 4).

Figure 4.

Magnetic resonance (water/LAVA Flex, axial and coronal sections) where it can be seen a nodular, hypervascular and intraparietal lesion of 21 mm, in the gastric small curvature (arrows).

Contemplating the possible diagnosis of a neuroendocrine tumour, a positron emission tomography with ⁶⁸Ga-DOTANOC (somatostatin receptors analogue) was performed. It did not show any abnormal gastric uptake.

Treatment

Laparoscopy revealed no signs of hepatic lesions, free intraperitoneal fluid or perigastric adenopathies. In the lesser curvature, there was a nodule in the gastric wall, seen as a small protuberance, not fixed to the surrounding tissues and with an apparent hard consistency.

A laparoscopic atypical gastric resection was performed.

There were no immediate complications.

Outcome and follow-up

Macroscopic examination of the resected specimen revealed an elastic and yellow solid tumour of 24×24×13 mm, totally contained in the stomach wall. Mucosa and serosa surfaces were smooth and brownish.

On microscopic examination, the solid tumour was formed by cells with vast granular cytoplasm (Periodic acid –Schiff positive) occupying the submucosal, muscularis propria and subserosal layers. The cells were positive for S100 protein, calretinin and CD34, and negative to CD117 and cytokeratin AE1/AE3. Surgical margins were tumour-free with a minimal margin distance of 0.4 mm. These results were compatible with a gastric GCT (figure 5).

Figure 5.

(A) H&E: neoplasm formed by big polygonal cells, with eosinophilic and granular vast cytoplasm. (B) and (C) Immunohistochemistry: neoplastic cells show positive expression for S100 protein (B) and calretinin (C).

Postoperative period was uneventful and the patient was discharged after 1 week.

At 1.5 years of follow-up, there were no signs of recurrence.

Discussion

GCTs are rare tumours of apparently neural origin. Histologically, they are composed of large polygonal cells, containing numerous eosinophilic granules.⁸

Immunohistochemical staining for S100 protein supports the proposed origin of the tumour to be Schwann cells.⁷

Most of gastric GCTs are asymptomatic, usually found incidentally on endoscopy.^{2 8} When present, the prevailing gastrointestinal symptoms described were dyspepsia and abdominal pain/discomfort.1 4 6 7 9 However, it is unlikely that these symptoms, in those particular cases, were caused by the tumour; once in the majority of them, the tumour was of small dimensions. These lesions end up to be observed during an upper endoscopy performed for non-specific gastrointestinal symptoms and probably not related to the GCT, as it happened in the presented case. Nonetheless, although these lesions are rarely associated with complications, when large, gastric GCTs may present as gastric outlet obstruction or massive upper gastrointestinal haemorrhage.^{1 8}

On endoscopy, GCTs are typically sessile, small in size (usually less than 20 mm), yellowish-white in colour, and covered by normal-appearing mucosa, the shape of which resembles a molar on the gingiva, making differential diagnosis with other submucosal lesions, such as lipomas, carcinoid or stromal tumours and hamartomas or metastatic tumours.⁸

Contrary to gastric GCTs, on endoscopy, gastric carcinoid tumours are usually multiple and often appear as small polypoid lesions with a central depression or central ulcer.²

EUS allows a detailed assessment of the gastric wall tumour invasion.⁵ On the EUS, gastric GCTs usually appear as hypoechoic and homogeneous lesions arising from the mucosa and/or submucosa. These EUS findings are similar to those of gastric carcinoid tumours making differential diagnosis very difficult.²

In 2015, Kim et al ² reviewed the EUS features of six recent cases of gastric GCTs and compared them with carcinoid tumours. They concluded that gastric GCTs were relatively inhomogeneous and more echogenic, compared with gastric carcinoid tumours.

Differential diagnosis with GISTs may also be extremely difficult, considering that endoscopic and EUS patterns are very similar. The stomach layer where the lesion originates may help distinguishing both lesions, since GCTs originate mostly in the second or third layer and GISTs in the fourth layer (muscularis propria).¹⁰

The echogenicity pattern also allows differentiation between GCTs and lipomas, which usually appear as homogeneous and hyperechoic.⁸

Diagnosis can be achieved by endoscopic biopsy through boring or performing a jumbo biopsy. However, up to 50% of the cases may not be conclusive.¹¹

Table 1 compares some clinical, imagiological and pathological features of GCTs, carcinoid tumours and GISTs.2 8 10–12

Table 1.

Comparison between GCTs, carcinoid tumours and GISTs

	GCTs	Carcinoid tumours	GISTs
Origin	Neural	Enterochromaffin cells	Mesenchymal stem cells
Immunohistochemistry	Positive to: S100 protein Neuron-specific enolase Vimentin PAS +	Positive to: Chromogranin A Synaptophysin	Positive to: c-Kit protein CD117
Symptoms	Usually asymptomatic Non-specific gastrointestinal symptoms Rarely: gastric outlet obstruction or GI haemorrhage	Usually asymptomatic	Depending on size: Asymptomatic GI haemorrhage Gastric outlet obstruction
Endoscopic appearance	Small yellowish nodules (95% of cases<2 cm)	Small polyps with a central depression/ulcer Solitary or in clusters	Submucosal, intramural or subserosal Covered by normal mucosa May present a central ulceration
EUS features	Hypoechoic Slightly heterogeneous Smooth margins Origin: usually second or third layer	Hypoechoic Homogeneous Well demarcated Origin: first, second or third layer	Hypoechoic More or less homogeneous More or less well demarcated Origin: usually fourth layer
Malignant potential	Usually benign	Maybe malignant (especially if>2 cm)	Maybe malignant: 10%–30% (especially if>4 cm)

EUS, endoscopic ultrasonography; GCTs, granular cell tumours; GISTs, gastrointestinal stromal tumours; PAS, Periodic acid –Schiff.

CT and magnetic resonance aspects are less referred to in the literature as they post a weak contribution to the differential diagnosis. However, they are mandatory to exclude extraparietal involvement, regional adenopathies or distant metastases.

Despite being expensive and probably not relevant for the treatment decision-making, a positron emission tomography with a somatostatin receptor analogue was performed. No abnormal gastric uptake was shown, allowing us to exclude a carcinoid tumour thanks to its high negative predictive value.

At least 50% of gastric GCTs are associated with synchronous oesophageal GCTs.² Therefore, if a gastric GCT is diagnosed, a careful endoscopic inspection will be required for evaluation of oesophageal GCTs.² In our case, there were no associated lesions.

GCTs of the gastrointestinal tract are usually benign, although malignant degeneration has been described for these lesions.^{2 9} Concerning the gastric location, only a case of malignant gastric GCT was reported so far.²

Features associated with malignancy include rapid growth to a size of 4 cm or more, cell necrosis, increased cellular atypia or high mitotic activity defined as a Ki-67 index of 10% or more.¹

Once the histological diagnosis of GCT is obtained, management of these lesions may vary from surveillance, endoscopic resection or surgical resection.

As with all gastrointestinal GCTs, there is no consensus on treatment because of the rarity of these lesions.¹¹

Some physicians suggest resection of all lesions because of the malignant potential. Other physicians advocate a less-aggressive strategy with endoscopic surveillance for asymptomatic small lesions.⁸

In a series from the Netherlands,¹³ specific cases of oesophageal GCTs left untreated showed either a stable tumour size or regression of the tumour. On the other hand, due to its recurrence rate and mortality, a malignant GCT should be considered a high-grade sarcoma with a negative prognosis.⁸

Considering the low incidence of malignancy, the surveillance strategy seems reasonable for asymptomatic gastric GCTs not amenable for endoscopic resection, especially in patients with poor surgical condition. Otherwise, due to the excellent prognosis while in the benign form, resection should be performed.

Endoscopic resection can be the treatment of choice in the absence of muscularis propria invasion. If muscularis propria or deeper layers are involved, surgery is advised.⁵

In the presented case, endoscopic resection was not a viable option as the EUS showed possible involvement of the stomach muscularis propria, which was confirmed by the anatomopathological examination.

Learning points.

• Granular cell tumours are rarely seen in a gastric location.

• They are usually asymptomatic making the diagnosis frequently incidental during an upper endoscopy.

• Differential diagnosis with carcinoid or stromal tumours makes preoperative diagnosis extremely challenging and only possible by endoscopic biopsy.

• Treatment may vary from surveillance to endoscopic or surgical resection.

• When performed, endoscopic or surgical resection is usually curative.