Current clinical management of gastrointestinal stromal tumor

Kazuya Akahoshi, Masafumi Oya, Tadashi Koga, Yuki Shiratsuchi, Kazuya Akahoshi, Masafumi Oya, Tadashi Koga, Yuki Shiratsuchi

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common malignant subepithelial lesions (SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1 (DOG1) is generally positive]. The prognosis of this disease is associated with the tumor size and mitotic index. The standard treatment of a GIST without metastasis is surgical resection. A GIST with metastasis is usually only treated by tyrosine kinase inhibitors without radical cure; thus, early diagnosis is the only way to improve its prognosis. However, a GIST is usually detected as a SEL during endoscopy, and many benign and malignant conditions may manifest as SELs. Conventional endoscopic biopsy is difficult for tumors without ulceration. Most SELs have therefore been managed without a histological diagnosis. However, a favorable prognosis of a GIST is associated with early histological diagnosis and R0 resection. Endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (EUS-FNA) are critical for an accurate diagnosis of SELs. EUS-FNA is safe and effective in enabling an early histological diagnosis and adequate treatment. This review outlines the current evidence for the diagnosis and management of GISTs, with an emphasis on early management of small SELs.

Keywords: Diagnosis; Endoscopic ultrasonography; Endoscopic ultrasonography-guided fine needle aspiration; Gastrointestinal stromal tumor; Therapy.

Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest. No financial support.

Figures

Figure 1
Figure 1
Rate of metastasis or tumor-related death according to tumor diameter and mitotic index. Created using reference[6].
Figure 2
Figure 2
Flow chart of diagnosis of gastrointestinal mesenchymal tumors using immunohistochemical or genetic analysis. 1Solitary fibrous tumors should be ruled out. Quoted and modified from reference[8]. GIST: Gastrointestinal stromal tumor.
Figure 3
Figure 3
Endoscopic images of subepithelial lesions that can be diagnosed only with endoscopic ultrasound findings and their specific endoscopic ultrasonography images. A: Endoscopic image of a gastric lipoma (arrow); B: Endoscopic ultrasound (EUS) image of A (high-echo mass); C: Endoscopic image of a gastric cyst; D: EUS image of C (anechoic mass); E: Endoscopic image of extra-gastric compression due to splenic artery aneurysm; F: EUS image of E [normal gastric wall is compressed by a splenic artery aneurysm(SAA) (arrow). SA: splenic artery]; G: Endoscopic image of gastric varices (arrow); H: EUS image of G [varices are present in the submucosa from the outside of the wall (V) (arrow)]. Quoted and modified from reference[38] with permission.
Figure 4
Figure 4
Differential diagnosis of subepithelial lesions by endoscopic ultrasound. Quoted and modified from reference[39] with permission. GIST: Gastrointestinal stromal tumor.
Figure 5
Figure 5
Endoscopic ultrasound images and corresponding endoscopic ultrasonography-guided fine needle aspiration specimens of hypoechoic solid tumors. A: Endoscopic ultrasound (EUS) image of a gastric gastrointestinal stromal tumor; B: EUS-guided fine needle aspiration (EUS-FNA) specimen tissue image of A (KIT-positive spindle-shaped tumor cells are observed); C: EUS image of gastric leiomyoma; D: EUS-FNA specimen tissue image of C [α-SMA-positive spindle-shaped tumor cells are observed; diagnosis of leiomyoma was made by immunohistochemical analysis, which revealed α-SMA (+), KIT (-), CD34 (-), and S-100 (-)]; E: EUS image of gastric malignant lymphoma; F: EUS-FNA specimen image of E (diagnosis of diffuse large B-cell lymphoma was made by CD20-positive lymphoid tumor cells); G: EUS image of rectal neuroendocrine tumor (NET); H: EUS-FNA specimen image of G (diagnosis of NET was made by typical findings of irregular nest of synaptophysin-positive epithelial-like cells). Quoted and modified from reference[38] with permission.
Figure 6
Figure 6
Proposed algorithm for management of subepithelial lesions. Quoted and modified from reference[21]. GIST: Gastrointestinal stromal tumor; GI: Gastrointestinal; SEL: Subepithelial lesion; EUS: Endoscopic ultrasound; EUS-FNA: Endoscopic ultrasound-guided fine needle aspiration.
Figure 7
Figure 7
Laparoscopic resection of a small gastric gastrointestinal stromal tumor. A: Laparoscopic view of a small gastric gastrointestinal stromal tumor (arrow) during resection; B: Postoperative endoscopy shows mild postoperative deformity (arrow). Quoted and modified from reference[77] with permission.
Figure 8
Figure 8
Contour maps for estimating the risk of gastrointestinal stromal tumor recurrence after surgery. Areas of colors according to the recurrence rate at the 10th year after surgical treatment of GIST: Blue-black: 0%-10%, Blue: 10%-20%, Light blue: 20%-40%, Gray: 40%-60%, Pink: 60%-80%, Red: 80%-90%, Dark red: 90%-100%. Reprinted from reference[87] with permission. E-GIST: Extra-gastrointestinal stromal tumor (arising outside the gastrointestinal tract).

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