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).
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,
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)
