This document provides an overview of gastrointestinal stromal tumors (GISTs). It discusses that GISTs are rare mesenchymal tumors of the gastrointestinal tract that arise from interstitial cells of Cajal. Key points summarized are: - GISTs most commonly occur in the stomach and small intestine in patients ages 60-65. Diagnosis involves endoscopy, biopsy, imaging, and genetic testing. - Surgical resection is the main treatment for localized GISTs. Factors like tumor size, location, and mitotic rate determine prognosis and risk of recurrence. - For high-risk cases, the drug imatinib can be given after surgery to reduce recurrence rates or before

1. Gastrointestinal Stromal Tumours
(GIST)
Presenter: Dr Lalthlamuana
Dnb Resident
General Surgery
Civil Hospital,Aizawl

2. Introduction
• Gist are rare mesenchymal tumours of GIT
• Belong to soft tissue tumours
• M/c Mesenchymal tumour of the GIT
• M/c Single type sarcoma
• Cell of Origin : Intestinal Cells of Cajal ( The pacemaker cell of the GIT
found in the myenteric plexus of the GIT)

4. Introduction
• Age: 60-65years of age
• Children and adolescents in a minority of cases
• Site: Stomach : (50-60%)
• Small bowel: (30-35%)
• Colon and rectum : 5%
• Esophagus: Least common ( <1%)
• Extra gastrointestinal GIST : Mesentry, Omentum, Retroperitonuem

5. Introduction
• Incidence : M >F
• Exception: SDH deficient Gist in which F >M
• Micro Gist: Gist < 1 cm
• Found in 10-25% of Gastric resections in a Japanese Study of 100
gastric surgeries

6. Clinical Presentation
• Soft, friable, highly vascular : Enhanced with IV Contrast
• Overt GI bleeding : 40%
• Abdominal Mass :40%
• Acute abdominal Pain
• Presentation
• 25% Emergency
• 25%Incidental
• Remaining : Compression, Anemia (due to chronic bleeding, Fatigue)

7. Diagnosis
• Endoscopy : Smooth contoured submucosal mass with possible central
umbilication

9. • Endoscopic Ultrasound (EUS):Hypoechoic mass arsing from the
muscularis propria

11. • CECT scan : Well-circumscribed,smooth,intramural mass with
exophytic growth

13. Diagnosis
• FDG Pet Scan: Fluoro-2-deoxy-D- glucose
positron emission tomography combined with CT (FDG PET-CT) may be
helpful to characterize masses that are ambiguous on CT, to monitor
response to tyrosine kinase inhibitor therapy, and to detect emergence of
drug-resistant clones

15. • Endoscopic or EUS guided or CT guided biopsy may be done
• Generally not done
• Tumour seedling
• Bleeding
Endoscopic biopsy :
• Less bleeding
• Metastatic disease
• If neoadjuvant imatinib planned.

16. Morphological Classification
1. Spindle Cell ( m/c )70 %
2. Epitheloid :20% Worst Prognosis, More Common In PDGFR α
mutated and SDH- Deficient GIST ,Found in Omentum and Mesentry
3. Mixed

18. Pathophysiology
• GIST are a relatively heterogeneous and complex group of lesions.
• KIT and PDGFRA they are the drivers of the disease .
• KIT and PDGFRA reside on chromosome 4q12 with both genes
encoding homologous transmembrane glycoproteins
• Gain-of-function mutations of these oncogenes can be found in
approximately 80% of GISTs.

21. EXON 11
• Most common KIT mutation
• Internal tandem duplication -- gastric GISTs that follow an
indolent course
• Deletions - aggressive clinical course with a higher risk of
recurrence and shorter survival.
• Exon 11 deletion involving codon 557 & 558 have poor disease
survival compared to other mutations.

22. Exon 9 :
• Small bowel involvement and a more clinically
aggressive neoplasm
Exon 13 & 17 :
• affect the tyrosine kinase domain
• less than 5% of sporadic GISTS .
• spindle cell morphology
• small bowel > stomach

23. PDGFRA
• 7% of GISTs harbour a mutation in PDGFRA
• MC – Stomach
• Epitheloid morphology
• MC - exon 18 affecting the TK2 domain
• PDGFRA JM domain (exon 12)– rare, can be point mutations,
deletions, or deletion insertions.
• PDGFRA exon 14 mutations are also typically missense mutations
that have been associated with a favorable clinical course

24. GIST – Wildtype
• 10% to 15%
• They make up a family of tumor subsets with different
pathogenetic backgrounds and, to some extent, different
natural histories .
• Their classification :
(1) SDH-deficient GISTs - young females (42%)
(2) neurofibromatosis (NF)-1–related GISTs
(3) BRAF V600E mutation , (13%)

25. CARNEY TRIAD
• GISTs + pulmonary chondromas + paragangliomas.
• These GIST arise in children and young adults of the female sex.
• Location : gastric and multifocal
• They metastasize to lymph nodes, have a rather indolent evolution.
• Given the absence of mutations to the SDH complex, a
posttranscriptional defect leading to dysfunctions of the SDH complex
may be in place.

26. Carney-Stratakis syndrome
• GIST + paragangliomas
• The median age of these patients is somewhat higher and the
female to male predominance is lower, but the course of
disease is indolent as well.
• Autosomal dominant disorder with incomplete penetrance
• Germline mutations in one of the subunits of the SDH gene, causing loss of
function of one of the SDH enzyme.

27. Differential Diagnosis

28. STAGING
• Conventional stage classification is seldom used .
• Clinicians mainly distinguish localized from metastatic disease and, if
the disease is localized and amenable to complete surgery, quantify
the risk of relapse .
• If localised , risk stratification helps to plan further treatment
• Current risk classification systems are based on the combination of
mitotic count, tumor size, and site of origin.

29. PROGNOSTIC FACTORS
• Large tumor size
• High mitotic counts
• Non-gastric location
• Presence of rupture
• Male sex

30. RISK STRATIFICATION
• Mitotic count :
Main prognostic factor, proportionally correlating to the risk of relapse.
• Tumor size :
Very small gastric lesions (<2 cm) - watchful surveillance if
incidentally discovered endoscopically
Lesions > 5 to 10 cm -- worse prognosis.
• Site Of Origin :
Gastric lesions have a better prognosis than small bowel and
rectal GISTs.

31. RISK STRATIFICATION TOOLS
• Armed Forces Institute of Pathology (AFIP) risk classification
• The Memorial Sloan Kettering Cancer Center (MSKCC)
nomogram
• The contour maps.
• NIH

33. Modified NIH Criteria

34. Management

35. SURGERY
• If disease is localized, surgery is the treatment mainstay.
• All GISTs ≥2 cm in size should be resected.
• 1-2cm, either observation or resection.
• Regardless of their size, any small GIST that is symptomatic
(e.g., bleeding from erosions through the mucosa) or increases
in size on serial follow-up should be resected

36. NCCN – Gastric GIST
Complete surgical resection is recommended for small gastric
• GIST <2 cm at high risk of recurrence based upon EUS
appearance such as :
• Irregular borders
• Cystic spaces
• Ulceration
• Echogenic foci
• Heterogeneity in appearance

37. PRINCIPLES OF SURGERY
• Goal : Complete gross resection with an intact pseudocapsule
• Surgery usually is a wedge or segmental resection of the involved gastric or
intestinal tract
• On laparotomy/laparoscopy, the abdomen should be thoroughly explored to
identify and remove any previously undetected peritoneal metastatic
deposits.
• A lymphadenectomy is not routinely required

38. • Extensive resection may be required as in total gastrectomy for a large
proximal gastric GIST, pancreaticoduodenectomy for a periampullary
GIST, or abdominoperineal resection for a low rectal GIST
• Tumor rupture or violation of the tumor capsule during surgery are
associated with a very high risk of recurrence, and therefore should be
avoided.

42. Adjuvant & Neoadjuvant therapy
-Imatinib mesylate – Most useful drug in maintaining progression free following
Compete surgical resection
– Imatinib a tyrosine kinase inhibitor effective in patients with c-KIT mutation
– They are usually ineffective in Wild type GIST
– Other drugs used are Sunitinib and Regorafenib

45. NEO ADJUVANT IMATINIB
• Preoperative imatinib can shrink gastric, periampullary, or
rectal GISTs to such an extent as to allow more limited excisions.
• Imatinib can then be continued postoperatively to complete the
adjuvant treatment
• Thus, if extensive surgery is required for complete tumor removal,
preoperative imatinib should be considered

46. • It is not given in patients with platelet-derived growth factor
receptor-alpha (PDGFRA) D842V mutation, or a succinate dehydrogenase
(SDH)-deficient or neurofibromatosis (NF)-related GIST, and instead
proceed directly to surgery.
• Usual dose - imatinib is 400 mg daily.
• Exon 9 KIT mutation - 800 mg per day
• Optimal duration -- "maximal response," usually not
exceeding 10 to 12 months

47. Management of advanced tumors
– In case the tumor deemed inoperable preoperative Imatinib can be
given
– Median time of response is 3 months and hence drugs given
preoperatively will range from 6-9 months
–Tumor response assessed by not tumor size but appearance of cystic
spaces and In homogeneity in enhancement

48. FOLLOW UP
• A computed tomography (CT) scan is recommended every 3 to 6 months for
3 to 5 years, then annually.
• 5 year survival rate is about 50%
• At least 50% develop recurrence or metastasis
• 85% of recurrence in Liver and peritoneum
• Median time to reoccur is about 2 years

49. GIST Updates
JOSENSU MODIFICATION OF THE NIH
HIGH RISK FEATURE OF GASTRIC GIST
• SIZE >10CM
• >10 MITOSIS/ 50 HPF
• TUMOUR NECROSIS
• >5CM SIZE + > 5 MITOSIS /50 HPF

50. HIGH RISK FEATURES IN A NON GASTRIC GIST
• SIZE >5CM OR
• >5 MITOSIS / 50 HPF

51. Privette classification of laparoscopic resection