Gastrointestinal Stromal Tumor Diagnostics

Laboratory Tests and Ancillaries

Mutational Analysis  

Mutational analysis may be performed when diagnosis is uncertain for mutations involving KIT and PDGFRA genes, and testing for these genes is strongly recommended. It is recommended for resectable gastrointestinal stromal tumor with significant morbidity. Testing for mutations is recommended prior to starting preoperative or neoadjuvant therapy to ensure if the tumor has the genotype that is responsive to the therapy. Mutational analysis predicts response to tyrosine kinase inhibitor (TKI) therapy. The presence and the type of KIT or PDGFRA mutation status can predict response to TKI therapy in patients with advanced or metastatic gastrointestinal stromal tumor. The presence of KIT exon 11 mutations is associated with better response rates, median progression-free survival (PFS), and median overall survival (OS) than KIT exon 9 mutations or non-mutated KIT or PDGFRA.  

Mutational analysis is also recommended for unresectable primary disease. Genotyping must be performed when medical treatment is planned as it helps in identifying genotypes that will benefit from Imatinib therapy and 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 using next generation sequencing (NGS) or immunohistochemistry (IHC).  SDH mutations commonly arise in the stomach of younger patients, frequently metastasize, may involve lymph nodes, and usually grow slowly, and are usually resistant to Imatinib.  

Other driver mutations (eg v-Raf murine sarcoma viral oncogene homolog [BRAF], type I neurofibromatosis [NF1], neurotrophic tyrosine receptor kinase [NTRK], and EGFR fusions) may be detected using NGS to identify potential targeted therapies. NF1-associated gastrointestinal stromal tumor commonly arises in the small intestine, may be multifocal, and often have an indolent behavior.  

Diagnostic Approaches  

For an esophagogastric or duodenal nodule with a size of <2 cm, laparoscopic or laparotomic excision is considered for histological diagnosis as endoscopic biopsy may be difficult. Rectal or recto-vaginal space nodules are biopsied or excised regardless of tumor size as the risk is high for a gastrointestinal tumor at this location. Laparoscopic or laparotomic excision may be performed for abdominal nodules not amenable to endoscopic assessment. Multiple core needle biopsies via endoscopic ultrasound (EUS) guidance or through US or computed tomography (CT)-guided percutaneous approach for a mass that is likely to have a multi-organ resection may be done. For obvious metastases, a diagnostic biopsy of the metastases is sufficient and may not need laparotomy.  

Biopsy  

Biopsy is necessary to confirm the diagnosis of gastrointestinal stromal tumor before the initiation of preoperative therapy. EUS- guided fine-needle aspiration (EUS-FNAB) or EUS-guided core needle biopsy (EUS-CNB) should be considered for very small gastric gastrointestinal stromal tumor <2 cm. High-risk pathological biopsy features include the presence of mitoses and/or tumor necrosis.  

Gastrointestinal Stromal Tumor_Diagnostics

• Mitotic rate
• Tumor size and site
  • Gastric gastrointestinal stromal tumors with a size of <2 cm are usually benign but colonic gastrointestinal stromal tumors with a size of <2 cm with mitotic activity can recur and metastasize
  • Small bowel or colonic gastrointestinal stromal tumors have an aggressive behavior compared with gastric gastrointestinal stromal tumor
• Surgical margin
• Tumor rupture (has a highly adverse prognosis)
• May be based on clinical parameters such as size and anatomic location in the absence of mitotic rate
• Factors associated with poorer disease-free survival (DES) include:
  • Presence of KIT exon 9 duplication
  • Presence of KIT exon 11 deletions
  • Nongastric site
  • Larger tumor size
  • High mitotic index
• Presence of PDGFRA exon 18 mutations were associated with better prognosis

Imaging

Abdominal or Pelvic Computed Tomography (CT) Scan With Contrast  

Abdominal or pelvic CT with contrast allows the assessment of the primary tumor and the extent of metastasis. It is the investigation of choice for staging and follow-up. It is the imaging of choice to evaluate the extent and presence or absence of metastasis at the initial staging workup for biopsy-proven gastrointestinal stromal tumor. For incidentally found mass on endoscopy, CT may be performed if EUS is not available. It is also the initial imaging done for large palpable masses or for patients presenting with hemorrhage, abdominal pain, or obstruction. Gastrointestinal stromal tumors usually show an extraluminal mass arising from the digestive tract wall. Lastly, it is the imaging option used to assess response to preoperative TKI every 8-12 weeks.  

Magnetic Resonance Imaging (MRI)  

An MRI gives better preoperative staging data regarding rectal gastrointestinal stromal tumors. It may provide tumor localization and show its relationship with adjacent organs. MRI can also be used to assess response to preoperative TKI every 8-12 weeks.  

Fluoro-deoxyglucose Positron Emission Tomography (FDG-PET)  

FDG-PET provides early neoplastic information and detects metabolic changes within the tumor earlier than the visible changes. It is beneficial in differentiating active tumor from necrotic or inactive scar tissue, malignant from benign tissue, and recurrent tumor from nondescript changes. It must be noted that a baseline must be performed first if it will be used for follow-up. It may be used as part of the pre-operative assessment and to assess responsiveness of the tumor after 2-4 weeks of preoperative TKI therapy.  

Endoscopic Ultrasound (EUS)  

EUS is a standard diagnostic tool for patients with esophagogastric or duodenal submucosal nodule <2 cm. It is the most useful assessment of masses located in the esophagus, stomach, duodenum, and anorectum. The potential high-risk features that may be seen with an EUS include cystic spaces, echogenic foci, heterogeneity, irregular border, and ulceration.  

Other Imaging  

Other imaging modalities that may be requested are endoscopy (if not yet done) and chest X-ray.