EUS-Guided Fine Needle Aspiration of Gastrointestinal Stromal Tumors: The GIST of the Matter

Our understanding of gastrointestinal stromal tumors (GIST) has evolved rapidly over the last few years. GISTs are now considered a distinct entity that arise from the interstitial cells of Cajal and exhibit a variable clinical course. One of the major breakthroughs was the discovery of CD117 antigen expression, also referred to as c-kit, on the tyrosine kinase receptor by GISTs. This antigen can be identified using immunohistochemistry (IHC), is expressed nearly universally by GISTs, and is critical in allowing differentiation of GISTs from myogenic, neurogenic, and other mesenchymal tumors. There has also been a paradigm shift in how the clinical behavior of GISTs is viewed; even though only 10–30% of GISTs are clinically malignant [1], all GISTs are now considered to have malignant potential with long-term follow-up [2]. This shift is based on a number of studies, one of which is a large series from Armed Forces Institute of Pathology (AFIP), where GISTs larger than 2 cm were found to have some finite risk of recurrence [3]. The natural history of smaller GISTs remains unclear at this point, though there have been reports of aggressive behavior in GISTs smaller than 2 cm in size [4]. Specific criteria that include size, mitotic count, and location of GISTs have been described to stratify risk of malignancy and tailor treatment [3, 5]. In this context, an accurate diagnosis, and if possible risk stratification of GISTs, is critical. Towards this end, endoscopic ultrasound (EUS) has become an important tool in our armamentarium. GISTs are typically seen to arise from the fourth layer of the gastric wall. While EUS imaging alone can accurately determine tumor size, wall layer of origin, echogenicity, and tumor margins, it is unable to reliably discriminate GISTs from other subepithelial tumors in all cases [6, 7]. Whether specific endosonographic features alone can help define low-risk and high-risk lesions also remains uncertain [8–10]. Consequently, many experts recommend EUSguided fine needle aspiration (EUS-FNA) for diagnostic sampling of subepithelial lesions when a diagnosis of GIST is being considered. However, in general, gastroenterologists continue to view EUS-FNA for subepithelial lesions with ambiguity. A recent survey of 134 members of the ASGE EUS special interest group found that only 58% believed that EUS combined with FNA was most predictive of a diagnosis of GIST [11]. This notion that EUSFNA is unrevealing in GISTs has been supported by reports of inadequate tissue acquisition with EUS-FNA with yields as low as 33.3% in all specimens [12]. Nevertheless, there is a growing body of more recent literature that has reported steadily improved diagnostic yields of EUS-FNA for GISTs. Watson et al. [13], in the current issue of Digestive Diseases and Sciences, provide additional data regarding the diagnostic yield and performance characteristics of EUS-FNA for GISTs. The authors retrospectively analyzed 65 consecutive patients who underwent EUS-FNA for 66 solid-appearing submucosal upper GI tract lesions over a 4-year period. A resection specimen was available and used as a reference in 28 patients. FNA was performed using either a 22-gauge or 19-gauge needle at the discretion of the endosonographer. A result was deemed diagnostic if a sufficient sample for cytopathologic evaluation and IHC analysis was obtained leading to a specific diagnosis. The authors found EUS-FNA to be diagnostic in 68%, V. Chandrasekhara N. A. Ahmad (&) HUP Division of Gastroenterology, Hospital of University of Pennsylvania, University of Pennsylvania School of Medicine, Ravdin 3 3400 Spruce Street, Philadelphia, PA 19104, USA e-mail: nuzhat.ahmad@uphs.upenn.edu