A 62-year-old woman undergoes upper GI endoscopy for chronic epigastric pain and is found to have a 2 cm submucosal bulge in the gastric fundus with intact overlying mucosa. The lesion appears smooth and yellowish. What is the most appropriate confirmatory investigation to establish the diagnosis of gastric gastrointestinal stromal tumor (GIST)?

## Diagnosis of Gastric GIST: Role of EUS-FNA with Immunohistochemistry ### Why EUS-FNA is the Gold Standard **Key Point:** EUS-FNA is the investigation of choice for diagnosing gastric GIST because it: - Allows direct visualization of the submucosal lesion and assessment of its layer of origin - Enables tissue sampling via FNA under real-time ultrasound guidance - Permits immunohistochemical staining (CD117, DOG1, CD34) for definitive diagnosis - Avoids full-thickness biopsy, which risks tumor seeding and perforation **High-Yield:** Gastric GISTs are mesenchymal tumors arising from the muscularis propria or submucosa. They are characterized by: - **CD117 (c-KIT) positivity** in >95% of cases (mutation in KIT gene) - **DOG1 (discovered on GIST) positivity** in >95% of cases (highly specific) - **CD34 positivity** in 50–70% of cases - Smooth, yellowish appearance with intact overlying mucosa (typical endoscopic finding) ### Diagnostic Algorithm for Submucosal Gastric Lesions ```mermaid flowchart TD A[Submucosal lesion on endoscopy]:::outcome --> B{Suspected GIST?}:::decision B -->|Yes| C[EUS assessment]:::action C --> D[EUS-FNA with tissue sampling]:::action D --> E[Immunohistochemistry: CD117, DOG1, CD34]:::action E --> F{CD117/DOG1 positive?}:::decision F -->|Yes| G[GIST confirmed]:::outcome F -->|No| H[Consider alternative diagnosis]:::outcome B -->|No| I[CT/MRI for characterization]:::action ``` **Clinical Pearl:** Small gastric GISTs (<2 cm) with low mitotic activity have excellent prognosis; EUS helps assess size, echogenicity, and risk stratification before deciding on surgery vs. surveillance. **Mnemonic — GIST Diagnosis (C-D-E):** - **C** = CD117 (c-KIT marker) - **D** = DOG1 (highly specific) - **E** = EUS-FNA (best sampling method) ### Comparison of Diagnostic Modalities | Investigation | Sensitivity for GIST | Tissue Diagnosis | Advantages | Limitations | |---|---|---|---|---| | **EUS-FNA** | High | Yes (immunohistochemistry) | Real-time guidance, low morbidity, tissue confirmation | Operator-dependent, small sample | | **CT-guided biopsy** | Moderate | Yes | Percutaneous approach | Invasive, risk of peritoneal seeding, not first-line | | **Contrast CT** | Moderate | No | Detects metastases, assesses size | No tissue diagnosis, cannot differentiate GIST from other mesenchymal tumors | | **Diagnostic laparoscopy** | High | Yes | Direct visualization, full-thickness biopsy possible | Invasive, risk of tumor seeding, reserved for surgical candidates | **Warning:** ~~Endoscopic forceps biopsy~~ is inadequate for submucosal lesions because it does not reach the muscularis propria and may miss the diagnosis. FNA is preferred.