Gist and its latest advancements

1. Gastrointestinal
Stomal Tumours
A seminar by Dr. Navam Dhiman
Junior Resident, Department of
General Surgery
Moderator: Dr. Vipan Kumar Sharma

2. Bibliography
• Books
• Baileys and Love A short practice of Surgery 28th edition
• Sabiston A textbook of Surgery 21st edition
• Washington Manual of Surgery 1st south Asia edition
• Journals

3. Contents
• Introduction
• Pathophysiology
• Aetiology
• Epidemiology
• Diagnosis
• Management

4. Introduction
Definition: Gastrointestinal stromal tumors (GISTs) are malignant
mesenchymal tumors with a variable clinical behavior, marked by
differentiation towards the interstitial cells of Cajal.
KIT
Proto-oncogene c-KIT is gene encoding
receptor tyrosine kinase, CD117
Seen in 80% of GIST.
Others - seminoma, melanoma, AML, mast
cell disease
PDGRRA
Platelet derived growth factor receptor A,
responsible for sustaining important
cellular process, CD140a
Seen in 2-15% of GIST
others – myeloid and lymphoid neoplasms,
nervous tumours

5. Incidence and epidemiology
• Males > Females
• Age (median) 60-65 years
• Incidence : from 0.4 to 2 cases per 100,000 per year; significant
variations in reporting
• Methodological issues, changes in diagnostic criteria
• WHO recent criteria for sarcomas and bone tumors - codes all GISTs,
regardless of size, site of origin and mitotic index, as malignant

6. Paediatric GIST
• a clinically and molecularly distinct
subset
• female predominance
• absence of KIT/PDGFRA mutations
• frequent mutations or silencing of
the four genes that encode the
subunits of the succinate
dehydrogenase (SDH) enzyme
complex
• gastric multicentric location
• possible lymph node metastases

7. Syndromes linked with GIST
Type 1 neurofibromatosis (NF1)
• marked by a germline mutation of the NF1 gene
• multicentric GIST predominantly located in the small bowel
Carney-Stratakis syndrome
• dyad of multifocal gastric GIST and paraganglioma
• late teenage years to the 30s
• no gender predominance
• lymph node metastatic potential
Carney triad syndrome
• multifocal gastric GISTs
• paraganglioma and pulmonary chondromas with onset in the teenage years
• female predominance

8. Diagnosis size <2cm
Esophagogastric & Duodenal GIST
• Standard approach :
Endoscopic ultrasound
(EUS)
• Difficult endoscopic
biopsy; open/laparospic
approach for
histopathological
diagnosis
• Majority have low or
very low risk; clinical
significance unclear.
Biopsy conclusive – resection (major morbidity expected at
esophago-gastric junction and D2 medial aspect)
Endoscopic resection preferred for minimising morbidity; if
tumour excision possible without tumour rupture
If a biopsy is not feasible or results in inadequate material for
diagnosis, active surveillance is generally recommended

9. Diagnosis size <2 cm
Esophagogastric & Duodenal GIST
• Patient can choose to have active surveillance
• No definitive evidence-based guidelines available
• Best approach endoscopic assessment after 3 months
• Duration of follow up can be increased based on growth status

10. Diagnosis
Rectal GIST
• Regardless of tumour size and mitotic rate
• Biopsy and excision after endorectal USG assessment and pelvic MRI
• In comparison to gastric GIST
• Risk of progression is more
• risk of surgical implication is more
• worse prognosis

11. Diagnosis size >2cm
• Biopsy and excision
• Associated with increased risk of progression if diagnosed as GIST
• Approach
• Endoscopic; not feasible  open/laparoscopic
• Likely multi visceral resection (?large mass)  multiple core biopsies should
be taken
• To be obtained via EUS or CT guidance
• If malignant
• Biopsy of malignant focus; comparison with primary foci
• Tumour specimen to be fixed in 4% buffered formalin solution

12. Pathological diagnosis of GIST
• Morphological and
immunohistochemistry
• CD117 KIT +ve in 80% of cases; -ve in 5%
of cases.
• mitotic count is a continuous variable;
indicator of prognosis
• Ki-67 analysis does not replace the
mitotic count; not part of established
prognostic systems
• SDH deficient GIST – in case of no
mutations of KIT/PDFGRA
mitotic count
the number of mitoses
on a total area of 5
mm2 [which should
replace, and is
equivalent to, the 50
high-power field area,
in order to avoid
variability]

13. Pathological diagnosis of GIST
• Mutational analysis
• for known mutations involving KIT and PDGFRA can confirm the diagnosis of
GIST, if doubtful (particularly in rare CD117/DOG1 immunohistochemically
negative GISTs).
• predictive value for sensitivity to molecular-targeted therapy as well as a
prognostic relevance
• inclusion in the diagnostic work-up of all GISTs should be considered
standard practice
• Rare
• BRAF mutation or an NTRK gene rearrangement may have therapeutic
implications.
• SDH-deficient GIST; without detectable mutations in KIT/PDGFRA

14. Staging and risk assessment
• Available risk classifications essentially refer to KIT-mutated GISTs
• Concept - Most relapses affect the peritoneum and the liver
• Mitotic rate, tumor size and tumor site - important prognostic factor
• Tumor rupture – regardless before or during surgery – additional prognostic
factor
• Mutational status - not been incorporated in any risk classification (at
present)
• Triple phase contrast-enhanced abdominal and pelvic CT scan
method of choice

15. Staging and risk assessment
• MRI pelvis – alternative procedure for pelvic GIST
• FDG ePET-CT/MRI, useful - early detection of the tumor response to
molecular-targeted therapy or when surgical resection of metastatic
disease is considered.

16. Management of loco-regional disease
• Standard – complete excision of lesion with no resection of clinically
negative lymph nodes
• Laparoscopic/robotic approach
• surgical oncology principles should be used.
• Discouraged in large tumors; risk of tumor rupture; increase in relapse
• Goal - R0 resection margin
• In low risk GIST at unfavourable locations; R1 resection margins can
be acceptable; given lack of any formal demonstration that R1 surgery
is associated with a worse overall survival.

17. History
• Recently recognised tumour entity earlier leiomyomas, leiomyosarcomas
and leiomyoblastomas
• Most common sarcoma of GI tract

18. Summary
Standard treatment: Surgery for local GIST. Imatinib for metastatic
disease.