GIST review

1. Gastrointestinal
Stromal Tumor
GIST
MELANIE CASTRO

3. Incidence
 Are the most common mesenchymal
tumors of the gastrointestinal tract 
ARE RARE TUMOURS (1/100 000/year)
 Neoplastic GIST cells seem to arise
from  the interstitial cells of Cajal in
the normal myenteric plexus
 The median age at diagnosis ranges
from 66 to 69 years
 Median size at presentation is
approximately 5 cm.

4. Clinical Presentation
 Small GISTs (<2cm): any symptoms and are detected
incidentally during abdominal exploration,
endoscopy, or radiologic imaging.
 Symptomatic: unspecific
 Long term disease: limited to early satiety, fatigue
secondary to anemia, intraluminal gastrointestinal
bleeding, pain or swelling.
 Emergency: Acute abdomen (as result of tumor rupture,
gastrointestinal obstruction, or appendicitis-like pain)

5. Diagnosis
 The standard approach to nodules ≥2 cm in size is
biopsy/excision, because, if GIST, they are associated with a
higher risk.
 GIST are soft ans fragile tumors  Endoscopic ultrasound guided fine
needle aspiration (EUS-FNA)
 Percutaneous image guided biopsy  Metastatic disease
 Biopsy is necessary to confirm the diagnosis of primary GIST before
the initiation of preoperative therapy

6. Pathology
Spindle cell type 70% Epithelioid cell type 20%
Leiomyoma
Leiomyosarcoma
Carcinoma
Metastatic Melanoma
Clear Cell Sarcoma

7. Immunohistochemistry
>95% CD117
60-70% CD34
15% Vimentin and
60% Smooth muscle actin
KIT-negative GISTs
 Precise diagnosis is
important because some
KIT-negative tumors are
known to be sensitive to
Imatinib
 80%  in genotypic
analysis shows mutations
in the PDGFRA gene
rather than KIT
5%
1. Overstaining for KIT
2. the intensity of KIT staining in GISTs is
variable
3. Staining intensity does not predict the
likelihood of a response to treatment

8. Molecular biology
 Most KIT mutations occur in the juxtamembrane
domain encoded by KIT exon 11 (EXON 9, 13, 17)
 Seem to be clinically more aggressive
 PDGFRA mutations are common in gastric GISTs and
most affect exon 18 in the tyrosine kinase domain 2.
 Approximately 10% to 15% of GISTs are negative for KIT
and PDGFRA gene mutations  Wild-type: are less
responsive to Imatinib based therapies and have a
poor prognosis.
 Primary resistance is most commonly seen in patients with KIT exon
9, PDGFRA exon 18, or wild-type GIST.

9. Prognostic Factors
Mitotic rate: 5 or more per 50 high power
fields (HPFs)
Tumor size: > 2 cm
Tumor location (patients with small
intestinal GISTs have the greatest risk).

10. Localized
Disease
Less 2cm > 2cm
Mestastatic
Disease
Treatment

11. Metastasis Treatment
 In locally advanced inoperable and metastatic patients,
IMATINIB is standard treatment (IIIA)  400mg
 Mutation exon 9  800mg. Better in terms of progression-free
survival (PFS)
 Treatment should be continued indefinitely, since
treatment interruption is generally followed by relatively
rapid tumour progression,

12. Localized tumor
< 2cm
Ecografic Ultrasound  HIGH-RISK features:
1. Irregular border
2. Cystic spaces
3. Ulceration
4. Echogenic foci, and heterogeneity

13. Localized tumor
> 2cm
Take in consideration:
1. RISK MORBILITY in surgery
 NO  Surgery
 YES  Pre-treatment with IMATINIB  Follow-up
2. Size
3. Margin excision R0 is not possible
IMATINIB??
• Lymphadenectomy is usually
unnecessary
• R0 excision is the goal (an
excision whose margins are
clear of tumor cells).

14. Post- resection
 Persistence gross residual diseases (R2 excision)
 Completely resected
 Preoperative Imatinib  Continue 2 years (NOT randomized trials)
 No pre- operatorative Imatinib  RISK OF RECURRENCE
IMATINIB??
Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of
recurrence: Final results of a randomized trial (SSGXVIII/AIO).
1) > 10.0 cm
2) Mitotic count greater than 10 mitoses per
50 high power fields of the microscope
3) Size > 5.0 cm AND mitotic count over 5
4) Tumor rupture before surgery or at surgery

15. When use Imatinib?
 In case of tumor rupture at the time of surgery  spillage of tumour
cells into the peritoneal cavity.
 Because rectal and gastroesophageal junction GISTs may respond
to preoperative imatinib (PRE)

17. World's Leading Culinary Destination 2014/2013/2012