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Gastrointestinal Stromal Tumor (GIST) : A Comprehensive Review

Dr. Manoj Bhandari, MS General Surgery Resident, Jan 23, 2024Jan 23, 2024

Last updated on January 23, 2024

Introduction:

  • Is a tumor of mesenchymal origin (previously thought to be of smooth muscle origin)
  • Most common mesenchymal neoplasm of GI tract
  • Arise from interstitial cells of Cajal
  • Incidence: 7-15 cases per million per year
  • 95% overexpress KIT (CD117), 80% express BCL-2 and 70% express CD34
  • KIT negative GIST will express PDGFRA
  • Sites: stomach (40-60%), SI (20-40%), colon/rectum (5-15%)
Surgical Anatomy of Stomach

Other facts:

  • Gastric GIST arise most commonly after 50 years
  • 5% of all GIST are associated with an underlying heritable mutation such as familial GIST syndrome (mutation in KIT and PDGFRA), NF-1, Carney-Stratakis syndrome (GIST+paraganglioma+/-pulmonary chondroma)
  • 2 pathological variants: spindle cell (70%)> epithelioid (30%)

Clinical features:

  • Non-specific symptoms: early satiety, bloating and vague abdominal pain
  • Bleeding: Malena or frank hematemesis
  • Tumor rupture with intra-abdominal hemorrhage is uncommon, but when it occurs, it requires urgent surgical intervention.

Diagnosis:

  • CECT with IV and oral contrast is the IOC: helps in diagnosis as well as staging of disease and is non-invasive
  • MRI is indicated only when there is contraindication of CT and for rectal GIST.
  • Staging of the disease is important especially when the patient is considered for neoadjuvant imatinib therapy.
  • PET-CT is the gold standard investigation for recurrent GIST.

Role of biopsy/tissue diagnosis in GIST (current consensus):

  • Is not recommended as it is a submucosal tumor (go for direct upfront surgery if there is high suspicion of GIST in imaging and the disease is operable)
  • If there is diagnostic dilemma then go for biopsy
  • EUS guided FNA is superior to UGI endoscopy guided biopsy as the tumor is submucosal.
  • Sensitivity and specificity of EUS guided FNA: 82% and 100% respectively

Treatment:

  • Mainstay of treatment: complete surgical excision
  • Indication of surgery: size >2 cm and symptoms
  • For tumors <2 cm:
    • If high risk features are present on endoscopy or EUS go for surgery
    • If not can be observed with 6-12 monthly EUS/endoscopy follow up

High risk features:

  • Irregular borders
  • Ulceration
  • Echogenic foci
  • Heterogeneity 

Choices of surgery:

  • Depending on tumor size and sites surgeries can vary from wide local excision, enucleation, sleeve gastrectomy, or total gastrectomy.

Aim of surgery:

  • R0 resection 
  • Lymph node dissection is not required as lymphatic metastasis is very rare 
  • Tumor should be handled carefully intraoperatively to avoid rupture or spillage.

Prognostication: 

  • 2 main prognostic factors:
    • Tumor size 
    • Mitotic rate
  • Based on long term follow up study of 1700 patients with Gastric GIST, malignant potential based on combination of these 2 factors have been established as shown below:
Malignant potentialComments Mortality 
Benign Size: up to 2 cmMitosis: up to 5/50 hpfNo tumor related mortality
Probably benignSize: 2-5 cmMitosis: same as above<3%
Uncertain/ low malignant potentialSize: up to 2 cmMitosis: >5/50 hpf–
Low to moderate Size: >10 cm Mitosis: same as benignORSize: 2-5 cmMitosis: >5/50 hpf12-15%
High Size: 5-10 cm Mitosis: >5/50 hpfORSize: >10 cmMitosis: >5/50 hpf49-86%

Role of adjuvant therapy:

  • Drug of choice: imatinib (tyrosine kinase inhibitor)
  • Indication: metastatic disease, resectable but moderate to high-risk malignant potential
  • Can be used as neoadjuvant therapy if the disease is non-metastatic but unresectable.

Landmark trials in GIST:

  • ACOSOG Z9001 trial:
    • C-KIT positive tumors 3 cm or larger who underwent complete resection found that patients treated with imatinib for 1 year had significantly improved 1 year recurrence free survival (98% VS 83%).
  • Scandinavian Sarcoma group trial:
    • Compared adjuvant course of imatinib (36 months VS 12 months) after resection of high-risk GIST
    • Result: extended course (36 months) had higher 5-year RFS and OS.
    • This trial has established a 3-year course as the standard of care after resection of high-risk GIST.

Algorithm for management of GIST:

gist approach

Reference: Sabiston textbook of surgery 21st edition

Dr. Manoj Bhandari
Dr. Manoj Bhandari, MS General Surgery Resident

He is an avid reader, guitar player, melodious singer and old songs lover. He has a passion for making medical knowledge accessible and comprehensive.

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PGMEE, MRCS, USMLE, MBBS, MD/MS Gastrointestinal systemGeneral SurgeryOncologyPathology

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Bhandari, M. Gastrointestinal Stromal Tumor (GIST) : A Comprehensive Review [Internet]. Epomedicine; 2024 Jan 23 [cited 2025 May 11]. Available from: https://epomedicine.com/medical-students/gastrointestinal-stromal-tumor-gist-a-comprehensive-review/.

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