Chines Expert Consensus of GIST

The Chinese Expert Consensus on Diagnosis and Treatment of Small Gastrointestinal Stromal Tumors (GISTs) is a comprehensive guideline developed by the CSCO Gastrointestinal Stromal Tumor Committee in collaboration with other professional associations. It aims to standardize the diagnosis, treatment, and management of small GISTs, defined as tumors measuring less than 2 cm in greatest dimension. Below is a detailed summary of the consensus:

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### **Definition and Epidemiology**

1. **Definition**: Small GISTs are defined as tumors measuring <2 cm in greatest dimension.

2. **Common Locations**: The stomach is the most common site for small GISTs, followed by the small intestine, colon, and rectum. Esophageal GISTs are rare, and colonic GISTs are extremely rare with an incidence rate of ≤0.1%.

3. **Detection**: The detection rate of small GISTs has significantly increased in recent years due to advances in diagnostic tools like endoscopy and imaging techniques.

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### **Biologic Behavior**

1. **Malignant Potential**: Small GISTs have varying malignant potential. Nongastric small GISTs (e.g., in the duodenum, small intestine, or rectum) exhibit worse behavior compared to gastric small GISTs.

2. **High-Risk Features**: Endoscopic ultrasonography (EUS) features such as hyperechoic foci, heterogeneity, irregular borders, and cystic changes are weak predictors of malignant potential.

3. **Aggressiveness**: While most small GISTs exhibit indolent behavior, some may show local progression or distant metastasis, particularly nongastric tumors.

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### **Diagnosis**

1. **EUS as First-Line Tool**: EUS is considered the most effective diagnostic tool for small GISTs. It provides detailed information on tumor size, internal structure, and relationship with surrounding tissues.

2. **Role of CT**: Contrast-enhanced computed tomography (CT) is used to aid in localization and follow-up, especially for tumors between 1–2 cm in size.

3. **Limitations of Endoscopy**: Gastrointestinal endoscopy is widely used but has limited specificity in differentiating between intramural lesions and extramural compression.

4. **Tissue Sampling**: EUS-guided fine-needle aspiration or biopsy is recommended for definitive diagnosis when necessary. In some cases, endoscopic resection can be used for both diagnosis and treatment.

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### **Differential Diagnosis**

Small GISTs must be differentiated from other submucosal lesions, including:

1. **Leiomyomas**: Benign tumors originating from the muscularis mucosae or muscularis propria.

2. **Neuroendocrine Tumors**: Malignant tumors originating from chromaffin cells, often found in the rectum.

3. **Lipomas**: Benign fatty tumors, commonly found in the gastric antrum or colon.

4. **Ectopic Pancreas**: Submucosal lesions often located in the gastric antrum, with variable EUS appearances.

5. **Schwannomas**: Tumors originating from Schwann cells, most commonly found in the stomach.

6. **Others**: Duplication cysts, glomus tumors, metastatic cancers, and early-stage lymphomas.

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### **Surgical Treatment**

1. **Gastric Small GISTs**:

• High-risk gastric small GISTs require surgery.
• Laparoscopic wedge resection is preferred for accessible lesions, but open surgery may be required for lesions in difficult locations like the esophagogastric junction.
• Endoscopic resection is feasible but should be performed cautiously in experienced centers.

2. **Duodenal Small GISTs**:

• Organ-sparing resection (e.g., wedge resection, segmental resection) is prioritized over pancreaticoduodenectomy.
• Endoscopic resection is not recommended due to the high risk of complications and malignancy.

3. **Small Intestinal Small GISTs**:

• Prompt resection is recommended due to the higher malignancy rate of small intestinal GISTs.
• Laparoscopy may aid in tumor localization but is not yet a standard approach.

4. **Colonic Small GISTs**:

• These are rare but should be resected upon detection.

5. **Rectal Small GISTs**:

• Minimally invasive techniques, such as transanal or robotic surgery, are preferred to preserve rectal function while ensuring complete resection.

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### **Endoscopic Treatment**

1. **Esophageal Small GISTs**:

• Endoscopic resection (e.g., endoscopic submucosal dissection, submucosal tunneling endoscopic resection) is safe and effective for small esophageal GISTs (<2 cm).

2. **Gastric Small GISTs**:

• Endoscopic submucosal dissection or endoscopic full-thickness resection is feasible for select cases.
• Complications like bleeding and perforation are common but manageable with advanced techniques.

3. **Duodenal, Small Intestinal, and Colorectal Small GISTs**:

• Endoscopic resection is not routinely recommended due to the thin walls of these organs and the higher malignancy risk of these tumors.

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### **Pathologic Diagnosis**

1. **Histology**: Small GISTs are typically classified into spindle cell, epithelioid cell, or mixed types. They often arise from the muscularis propria and exhibit low mitotic activity.

2. **Immunohistochemistry**: Markers such as CD117, DOG1, CD34, and Ki-67 are critical for diagnosis.

3. **Genetic Testing**: Testing for KIT and PDGFRA mutations is recommended, especially for high-risk tumors with a mitotic index >5 per 5 mm².

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### **Molecular-Targeted Therapy**

1. **Adjuvant Therapy**: Imatinib is recommended post-resection for tumors with a mitotic index >5 per 5 mm² or high-risk features.

2. **Genetic Testing**: Helps predict treatment efficacy and guides the use of targeted therapy.

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### **Surveillance Strategy**

1. **Observation**: Observation is acceptable for asymptomatic gastric small GISTs with informed consent, but nongastric small GISTs require resection.

2. **High-Risk Features**: Surgery is indicated if high-risk features (e.g., irregular borders, cystic changes) are detected during surveillance.

3. **Monitoring Frequency**:

• Tumors >1 cm: Monitor every 6–12 months.
• Tumors <1 cm: Monitor at least once every 2 years.

4. **Combined Approach**: EUS and enhanced CT should be used together for follow-up to ensure accurate monitoring of tumor growth and behavior.

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### **Key Takeaways**

1. Small GISTs are defined as tumors <2 cm in size, with the stomach being the most common location.

2. While most small GISTs exhibit benign behavior, nongastric tumors and those with high-risk features may have malignant potential.

3. EUS is the first-line diagnostic tool, with CT used for localization and follow-up.

4. Differential diagnosis is crucial to distinguish small GISTs from other submucosal tumors like leiomyomas, lipomas, and neuroendocrine tumors.

5. High-risk small GISTs require surgical resection, with minimally invasive techniques preferred for accessible lesions.

6. Endoscopic resection is feasible for select gastric and esophageal small GISTs but is not recommended for duodenal, small intestinal, or colorectal GISTs.

7. Pathologic diagnosis relies on immunohistochemistry (e.g., CD117, DOG1) and genetic testing (e.g., KIT, PDGFRA).

8. Adjuvant imatinib therapy is recommended for high-risk tumors.

9. Surveillance strategies depend on tumor size and location, with regular monitoring using EUS and CT.

This consensus provides a detailed roadmap for clinicians managing small GISTs, emphasizing individualized treatment based on tumor characteristics and location. It also highlights the importance of early detection, accurate diagnosis, and appropriate treatment to improve patient outcomes.