Management of GIST

1. Gastrointestinal
Mesenchymal
tumors
Dr.P.Viswakumar, M.S
PSG Institute of Medical science

2. Objectives
At the end of the class student should be aware of ‘what is gastrointestinal stromal
tumor and how to identify both clinically and pathologically and overview of
management of resectable and unresectable tumors’.

3. Topics covered
– Introduction
– Epidemiology
– Histopathology
– Clinical manifestation
– Diagnostic workup
– Treatment (Surgical and medical)
– Management of advanced tumors
– Prognosis

4. Introduction
– Gastrointestinal mesenchymal tumors –Subepithelial neoplasms
Broadly divided into
1) GIST – Gastrointestinal stromal tumors
2) Mesenchymal GI neoplasm like in anyother organ
(Leiomyoma, Leiomyosarcoma,Lipoma,desmoid
tumors,Schwannoma,etc)

5. Epidemiology
GIST
– Location– MC in the Stomach and proximal small intestine
Other less common site – Mesentry,Omentum and peritoneum
– Incidence – Both Male and female have equal incident rate
< 1 % of Primary GI cancer but true incident varies

6. Genetical
– Familial GISTs – 5 % of patients
– Associated Syndromes-
- Neurofibromatosis type 1
- Carney- stratakis syndrome
- Primary familial GIST syndrome
– Pediatric GIST – Rare but arise in within above defined syndrome esp as ‘Carney triad’ –
Pulmonary condroma,GIST and Extra adrenal paraganglioma

7. Histopathology
Cell of Origin ?
- ? Smooth muscle cells of GIT
- ? Autonomic nerves of GIT (Intertitial cells of Cajal)
Then how they are identified ?
- CD117 antigen – Part of KIT Protooncogene (c-KIT)
90% of GIST positive for c-KIT expression
- Another gene encoding PDGRA( platelet derived growth factor alpha) also mutated in
remaining 10 % cases
- Remaining few – Mutations in gene encoding SDH (Succinate dehydrogenase) – pediatric
GIST

8. D/D for Subepthileal tumors
– Leiomyoma
– Leiomyosarcoma
– Malignant melanoma
– Schwannoma
– Malignant peripheral nerve sheath tumors
With light microscopy defining GIST from above tumors are difficult and hence
require immunohistochemistry

9. Type CD117 CD34 SMA* S100 Protein Desmin PKC-theta DOG-1
GISTs + (>95
percent)
+ (60-70
percent)
+/- (30-40
percent)
- (5 percent +) Very rare
+
(72 percent)
+ (97 percent)
Leiomyoma -
+ (10-15
percent) + - + -
Leiomyosarco
ma - - + - + + (10 percent) -
Schwannoma - - - + _ + (10 percent) -
Immunohistochemical schema for the differential diagnosis of spindle cell tumors of the gastrointestinal tract
DOG-1: Discovered in GIST-1; PKC-theta: protein kinase C theta.
• Alpha smooth muscle actin.
Source Ref : Uptodate 2017
Immunohistochemistry Profile

10. Cellular morphology
– Spindle cell type - 70%
– Epitheloid type – 20%
– Mixed type – 10 %

11. Spindle Cell types : Shows elongated nuclei within esonophi
lic cytoplasm
Epitheloid cells with round central nuclei within esonophilic
Or clear cytoplasm
Courtesy : Uptodate.com 2017

12. Leiomyoma and leiomyosarcoma
– Small and well circumsbscribed
– Arise from muscularis propria
– Growth may be intraluminal,Extraluminal or mixed dumb bell tumors
– Size range <0.5 cms to 30cms
– Distinction between leiomyoma and leiomyosarcoma done by light microscopic
fingings (Shown below)

13. Rectal Leiomyoma(Low power view) Jejunal Leiomyoma ( Medium power view)
Image courtesy : Uptodate.com c. 2017

14. Small bowel leimyosarcoma low and High power views
The high power view reveals pleiomorphic spindle cells with nuclear atypia, hypercellularity,
and several mitotic figures

15. Clinical presentation
– Overt GI bleeding – 40 %
– Abdominal Pain – 20 %
– Abdominal mass – 40 %
Few may present with intestinal obstruction due to lead point
causing intussuception.
– GIST can occur anywhere in body from mouth to anus,Stomach being most common site
– Metastatize to Liver and peritoneum and rarely to Lymphnodes
– Severe hypoglycemia due to paraneoplastic tumor production of insulin like growth factor II

16. Diagnostic work up
– Contrast enhanced CT - To identify mass location and metastatic spread
– UGI Scopy – Appear as submucosal mass with smooth margins,normal overlying mucosa and
bulging into gastric lumen and ulceration seen occasionally
Image courtesy : Uptodate.com 2017

17. Endoultrasound
EUS accurate method
for distinguishing
leiomyoma from other
submucosal lesion
EUS guided FNAC
helpful to delineate
other tumors
Image courtesy : Uptodate.com 2017

18. – Preoperative biopsy – Not needed in resectable cases but incase of boderline resectable or
unresectable tumor preoperative biopsy is essential
– PET scan – Mostly used to monitor the response for tumor chemotherapy

19. Management

20. Surgical management
– Goal of Surgical management
- Complete tumor resection with intact pseudocapsule
- Segmental resection of stomach or Small intestine performed to
achieve negative margins
- Wider margin with uninvolved tissue is of no benefit.
- Routine Lymphadenectomy not necessary

21. Adjuvant & Neoadjuvant therapy
– Imatinib mesylate – Most usefull 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

22. 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
inhomogenicity in enhancement
– Liver metastasis can be managed similar to colorectal mets except neo and
adjuvant imatinib had better survival rate

23. Prognosis
– GIST is deemed to be malignant
– The factors affect recurrence of tumor are importantly assessed
– Tumor size and mitotic index are the important predictor of distant
metastasis,Recurrence and survival.
– So tumor >=2cms are invariably resected
– Tumor <=1 cm can be observed
– Tumor 1-2 cms size ambiguity still exists
– Mitotic index >5/50 HPF and >5cms or tumor >10cms or >10/HPF in tumor of
any size are considered high risk.

24. Reference
– Schakelford’s Surgery of Alimentary Tract,7ed
– Uptodate.com from Wolter-Kluwer copyrighted @ 2017