Biopsy

• Morphologic diagnosis from histologic microscopic examination is the standard for diagnosis
  • Diagnosis of primary gastrointestinal stromal tumor (GIST) is confirmed w/ a biopsy before starting preoperative therapy

• GISTs are soft and fragile & may cause hemorrhage & increased dissemination
  • Pseudocapsule should be preserved & tumor spillage avoided

• Endoscopic ultrasound-fine-needle aspiration (EUS-FNA) biopsy is preferred over percutaneous biopsy & may be done in GISTs <2 cm
• Metastatic disease may be confirmed via percutaneous image-guided biopsy

Histopathology summary should include the following:

• Diagnosis
  • Tumor type (eg spindle, epithelioid or mixed), mitotic rate
  • Presence or absence of necrosis, hemorrhage & lymphovascular invasion
  • Invaded structures

• Immunohistochemistry result, KIT expression status
• Margin evaluation
• Prognostic category; prognostic factors include:
  • Mitotic rate
  • Tumor size & site
    • Gastric GISTs <2 cm are usually benign but colonic GISTs <2 cm w/ mitotic activity can recur & metastasize
    • Small bowel or colonic GISTs have an aggressive behavior compared w/ gastric GISTs
  • Surgical margin
  • Tumor rupture (has a highly adverse prognosis)

• Recommendation on a multidisciplinary team meeting

• Abdominal/pelvic computed tomography (CT) scan w/ contrast
  • Allows assessment of primary tumor & extent of metastasis; investigation of choice for staging & follow-up
  • For incidentally found mass on endoscopy, CT may be performed if endoscopic ultrasound is not available
  • Initial imaging done for large palpable masses or for patients presenting w/ hemorrhage, abdominal pain or obstruction
  • Gastrointestinal stromal tumor (GIST) usually shows an extraluminal mass arising from the digestive tract wall

• Magnetic resonance imaging (MRI)
  • Gives better preoperative staging data regarding rectal GISTs
  • May provide tumor localization & relationship w/ adjacent organs

• Positron emission tomography (PET)
  • Provides early neoplastic information
  • Detects metabolic changes within the tumor earlier than the visible changes
  • May be used as part of the pre-operative assessment
  • May also be used to assess responsiveness of the tumor to Imatinib

• Chest x-ray
• Endoscopic ultrasound (EUS)
  • Should be performed first if submucosal mass is an incidental endoscopic finding
  • Important in diagnosis of small masses (<2 cm)
  • Most useful in assessment of masses located in the esophagus, stomach, duodenum & anorectum
  • Potential high-risk features include cystic spaces, echogenic foci, heterogeneity, irregular border, & ulceration

• Endoscopy (if not yet done)
• Mutational analysis
  • Performed when diagnosis is uncertain for mutations involving KIT & platelet-derived growth factor receptor alpha (PDGFRA) genes
    • Testing for these genes is strongly recommended
  • Genotyping must be performed when medical treatment is planned
    • Helps in identifying genotypes that will benefit from Imatinib therapy & the appropriate dose for treatment of KIT exon 9 mutations
  • If KIT or PDGFRA mutations are lacking, consider testing for germline mutations in the succinate dehydrogenase (SDH) genes

Diagnostic Approaches

• For a <2-cm esophagogastric or duodenal nodule, laparoscopic/laparotomic excision is considered for histological diagnosis as endoscopic biopsy may be difficult
• Rectal or recto-vaginal space nodules are biopsied/excised regardless of tumor size as risk is high for a GIST at this location
• Laparoscopic/laparotomic excision may be performed for abdominal nodules not amenable to endoscopic assessment
• Multiple core needle biopsies via endoscopic ultrasound guidance for a mass that is likely to have a multi-organ resection
• For obvious metastases, diagnostic biopsy of the metastases is sufficient & may not need laparotomy