GIST Tumors

GIST Tumors

1. Epidemiology
• most common sarcomatous tumor of the GI tract
• the stomach accounts for 40% - 60% of cases; jejunum/ileum, 25% - 30%; duodenum, 5%; and colon/rectum, 5% - 15%
• approximately 5000 – 6000 cases/year
• mean age at diagnosis is 60 years
• most cases arise sporadically, although familial syndromes exist (neurofibrosis 1, von Hippel-Landau disease, GIST-paraganglioma syndrome (Carney triad))


2. Pathogenesis
• GIST tumors arise from the interstitial cells of Cajal, a gastrointestinal pacemaker cell
• most GIST tumors (80%) over express the kit proto-oncogene, which is a transmembrane receptor tyrosine kinase
• a mutation in the kit gene leads to constitutive activation and oncogenic signaling in the cell
• GIST tumors express the CD117 antigen, which can be identified by immunohistochemical staining
• the majority of GIST tumors lacking kit mutations have an activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA)


3. Presentation
• some GIST tumors are asymptomatic and are found incidentally at surgery, during endoscopy, or on imaging
• additionally, some GIST tumors present with nonspecific symptoms like early satiety, bloating, or abdominal pain
• bleeding is the most common overt symptom: melena is most common, but frank hematemesis may occur
• rarely, tumor rupture may occur, leading to life-threatening intraperitoneal hemorrhage
• some patients present with obstructive symptoms
• between 15% - 50% of patients may have metastatic disease at presentation
• most common sites of metastasis are the liver, omentum, and peritoneum; lymph node metastases and extra-abdominal metastases are uncommon (<5%)


4. Diagnosis
1. Endoscopy
• GIST tumors appear as a smooth, round, submucosal tumor, occasionally with a central ulceration



• endoscopic biopsy has a low diagnostic yield, and a tissue diagnosis is not mandatory for a resectable lesion
• endoscopic ultrasound-guided FNA is more accurate and should be done if neoadjuvant therapy is being considered or to confirm the diagnosis of metastatic disease


2. CT Scan
• used to assess resectability and for the presence of metastatic disease
• GIST tumors appear as a solid, smoothly contoured mass that enhances brightly with IV contrast



5. Prognostic Factors
• there are 3 well established poor prognostic factors: tumor size > 10 cm, mitotic index > 5/HPF, and tumor site of origin (small intestine)
• mitotic index is the strongest predictor of tumor recurrence
• small bowel GISTs have a higher rate of recurrence than gastric GISTS with similar sizes and mitotic counts
• tumor rupture, either spontaneously or at surgery, has also been verified as an independent risk factor that negatively affects disease-free survival
• various prognostic models exist that are based on tumor site, size, mitotic index, and presence of rupture


6. Treatment
1. Surgery
• only potential curative treatment
• all tumors > 2 cm should be resected
• most tumors between 1 and 2 cm should likely be resected, since no GIST tumor can be considered benign
• gastric GISTs < 1 cm can be followed, but any small bowel or colon GIST should be resected, irrespective of size
• ideal margin of resection is unknown
• goal should be an R0 resection, but there is no data to suggest that an R1 resection needs re-excision
• wedge resection or segmental resection are the most common operations performed
• rarely a total gastrectomy is required
• involved organs should be resected en bloc
• lymphadenectomy is not required since nodal metastasis is rare
• tumor rupture at the time of surgery is associated with increased recurrence
• ~ 50% of patients develop recurrence by 24 months


2. Adjuvant Therapy
• imatinib (Gleevec), a tyrosine kinase inhibitor, improves survival in high-risk patients
• eligible patients have tumors > 3 cm or who have a mitotic index > 5/hpf
• length of therapy should be at least 3 years
• imatinib may also be used in a neoadjuvant setting to improve resectability