What to do with the Incidental Asymptomatic Small Gastric Subepithelial Lesions. Facts? Recommendations? Dilemmas?

    

    

    Figure 1:  An incidental small hypoechoic lesion (calipers) from muscularispropriain gastric wall (15.3×8.2 mm). Endoscopic ultrasound assisted fine needle
aspiration was performed due to the presence of echogenic foci and the result was gastrointestinal stromal tumor.
    
    

The diagnostic yield of EUS-FNA for small gastric hypoechoic SELs was reported as 73% (66/90 patients) in a recent study [3]. Histological diagnosis of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed 44 GISTs, 1 glomus tumor, 1 SEL like cancer, 1 malignant lymphoma, 14 leiomyomas, 4 ectopic pancreas, and 1 neurinoma. Of those lesions leiomyoma, ectopic pancreas, and neurinoma were benign lesions that do not warrant further treatment [3]. Among those patients, 44 were surgically resected and the diagnostic accuracy of EUS-FNA with reference to post-operative pathology results was 98% (43/44). Thus, GIST is the most common etiology of hypoechoic gastric SELs and EUS-FNA may count an accurate and safe method in the diagnosis of gastric SELs smaller than 2 cm.

The EUS features of the gastric GISTs for prediction of the malignant potential were investigated. According to the study by Chen et al., tumor size greater than 5 cm, was the only independent risk factor for malignancy (intratumoral calcification and cysts, surface ulceration, patient’s age) [4]. Nevertheless, when the GISTs of between 2 to 5 cm sizes were considered, the risk stratification based on the size of tumor could not be accomplished [5].

At present, although EUS-FNA is considered the procedure of choice for preoperative diagnosis of GIST by immunohistochemical analysis of the sample for c-KIT [6], it provides inadequate material in up to 33.3% of the cases. Particularly, smaller tumors are technically more difficult to obtain adequate histological samples compared to larger ones [7]. So, the diagnosis of small GISTs may be only presumptive based on the EUS appearance but also performing EUSFNA and management decision may be challenging. Nevertheless, GIST appeared to be the most common diagnosis among the MUSCULARIS PROPRIA-SELs in many studies evaluating the post-operative results. In one study, post-operative histological examination revealed GIST in 16 of 19 (84.2%) resected gastric MUSCULARIS PROPRIA-SELs =3 cm in size (the others were 2 schwannomas and 1 leiomyoma) [8]. Even in the case of a GIST diagnosis accomplished by EUS-FNA, evaluation of the malignant potential of the tumor based on the mitotic index may not be possible due to the lack of as sufficient material as required for prompt investigation. Thus EUS-FNA may not change the management strategy at least in a significant subset of patients with asymptomatic small MUSCULARIS PROPRIA-SELs.

The National Institutes of Health (NIH) consensus [9] classified GISTs into very low-, low-, intermediate-, and high-risk categories by using the size and mitotic count of the lesions. Furthermore, Miettinen and Lasota [10] indicated that GISTs =20 mm with a mitotic index of =5/50 HPF have no metastasis risk, thus they defined these lesions as benign, although NIH has avoided such a category. Nevertheless, obtaining sufficient material from a small SEL to scrutinize its malignant potential by assessing the mitotic count may be technically difficult. In such cases, the indirect features suggesting malignant potential during EUS examination may give an idea and help to individualize the treatment especially for those who are not fit for surgery. Those features are large size (=2cm), irregular borders, heterogeneous echotexture, presence of anechoic (cystic) spaces, echogenic foci, and growth during follow-up. Contrast-enhanced endoscopic ultrasound which is not available widely outside of Europe may also give clues suggesting malignant potential that are irregular vascular patterns on vessel images, heterogeneous enhancement due to avascular areas (necrosis) on perfusion images [8].

How to Follow Up the Small Muscularis Propria Subepithelial Lesions

The frequency of follow-up duration of small SELs suggestive of GIST is controversial in different guidelines. The American Gastroenterological Association (AGA) recommends surveillance for <30 mm lesions without concerning the endosonographic features [11]. The US National Comprehensive Cancer Network (NCCN) avoids making a clear statement for the small gastric GISTs (<20 mm) because of the insufficient data, but recommends resection of the small lesions with high-risk EUS features, and endoscopic surveillance at 6- to 12-month intervals for the lesions without high-risk features [12]. European Society for Medical Oncology (ESMO) guidelines suggest a short-term first control (e.g. at 3 months) continuing with a longer interval follow-up schedule in case of no growth, if follow-up strategy is chosen for small lesions [13]. Japanese guidelines recommend that lesions <20 mm in size and without ulceration or surface depression can be managed with endoscopic follow-up once or twice a year [14]. There are no large-scale investigations providing evidence for the effectiveness of these follow-up schedules. The study published by our group has shown that small hypoechoic SELs of <2 cm originating from muscularis propriain stomach suggestive of GIST lesions with EUS survive disease free for a mean duration of 4 years although most patients in our series had much longer surveillance [15]. Therefore, we support the notion of conservative management of small hypoechoic SELs originating from muscularis propria of gastric wall and we summarize it on Figure 2. Our results suggest that following up of those small asymptomatic muscularis propria- SELs detected incidentally during upper gastrointestinal endoscopy without any high risk echogenic features for malignancy not less than 4 years is sufficient. We believe, the guidelines regarding the followup recommendations of small hypoechoic muscularis propria SELs of stomach suggestive of GISTs should be revised as they currently recommend EUS follow-up every 3 to 12 months after the initial examination [16].

    

    

    Figure 2:  Suggested approach for the management of small gastric MUSCULARIS PROPRIA-SELs.
CE-EUS: Contrast-Enhanced EUS; DOG-1: Discovered on GIST-1; EUS: Endoscopic Ultrasonography; GIST: Gastrointestinal Stromal Tumor; IHC:
Immunohistochemistry; MP: Muscularispropria; PDGFR-a: Platelet Derived Growth Factor Receptor Alpha; SEL: Subepithelial Lesion [16].