1. Gastrointestinal Stromal Tumors

2. Definition of Gastrointestinal Stromal Tumor
the most common mesenchymal malignancy of (GI) tract
the diagnostic criteria for GIST remained controversial and somewhat confusing

3. Pathology Terms that Encompass the Spectrum of Gastrointestinal Stromal Tumors
Leiomyoblastoma
Gastrointestinal leiomyosarcoma
Gastrointestinal autonomic nerve tumor
Gastrointestinal pacemaker cell tumor
Plexosarcoma
Gastrointestinal neurofibrosarcoma

4. KIT expression is noted in the vast majority (more than 95%) of GISTs,
KIT is not expressed by other smooth muscle tumors of the GI tract nor by other stromal tumors outside of the GI tract
The origin of the neoplastic cells of GIST remains a matter of active investigation

5. the KIT protein serves as a transmembrane RTK; the CD117 antigen can be detected by immunohistochemical staining as a marker for the presence of the KIT protein

6. Clinical Considerations
adults at a median age of 58 years
higher in men
(60% to 70%) stomach, (20% to 30%) small intestine, and fewer than 10% in the esophagus, colon, and rectum. GISTs can also occur in extraintestinal abdominopelvic sites such as the omentum, mesentery, or retroperitoneum.

7. abdominal pain
abdominal mass,
nausea, vomiting,
anorexia
weight loss.
acute hemorrhage

8. The vast majority of GIST metastases at presentation are intra-abdominal, either to the liver, omentum, or peritoneal cavity.
Metastatic spread to lymph nodes or to extra-abdominal sites via lymphatics is very rare

9. Diagnostic EvaluationCT
MRI
upper GI endoscopy
Ultrasonographically enhanced endoscopy

10. an epithelioid (larger, rounder cells) or spindle cell histology.
expert pathologists can define a rare subset (fewer than 5%) of GISTs that fail to express CD117, and these are most likely to be driven by an alternative kinase such as PDGFRA
There are no definitive diagnostic criteria of CD117-GIST unless the tumor genotype analysis indicates a KIT or PDGFRA mutation characteristic of GIST

11. DDX soft tissue sarcomas Ewing's sarcoma and angiosarcoma
small cell lung cancers,
melanomas
desmoid tumors
seminomas,
ovarian carcinomas,
mastocytomas,
neuroblastomas,
adenoid cystic carcinomas,
subsets of lymphoma and acute myeloid leukemia.

12. Metastatic
Or un resectable
h risk
I risk
low risk
Very low risk
اندازه
هر اندازه و میتوز
بیشتر از 10 یا 5 با متیوز متوسط یا زیاد
کمتر از 3
بین 2 تا 5
کمتر از 2
سانتیمتر
میزان میتوز
متوسط کم

13. some contribution to prognosis
Other factors, such as the specific histologic subtype (epithelioid vs. spindle cell), the degree of cellular pleomorphism, and patient age,
Recurrence and survival rates have been reported to correlate with the location of the primary GIST lesion, with small bowel tumors showing a somewhat worse prognosis

14. Diagnostic Imaging PET
FDG-PET imaging can detect lesions at least 1 cm CT
MRI

15. Management of Metastatic, Unresectable, or Recurrent Gastrointestinal Stromal Tumor
Cht: P-glycoprotein (the product of the multidrug resistance-1 [MDR-1] gene) and the multidrug resistance protein-1 MRP1
RT: bleeding , pain

16. prolonging the survival
First Molecularly Targeted Kinase Inhibitor Therapy for Gastrointestinal Stromal Tumor: Imatinib Mesylate
FDA approved the use of imatinib for the treatment of metastatic or unresectable GIST
objective responses
control of symptoms
prolonging the survival

17. FDA approval of imatinib for dermatofibrosarcoma protuberans

18. toxicities nausea, vomiting, and severe edema, diarrhea
myalgia or musculoskeletal pain
skin rashes
headache
Myelotoxicity
Cardiotoxicity
hemorrhagic events
tachyphylaxis

19. 18FDG-PET represents a useful diagnostic technique for very early assessment of response to imatinib therapy.
The optimal dose of imatinib for treatment of advanced GIST remains uncertain

20. some marginal benefit might be obtained from modest dose escalation of imatinib in a subset of patients whose disease progresses despite continued dosing at lower therapeutic levels of imatinib

21. The optimal duration of imatinib
continued dosing with imatinib as long as the disease is not progressive

22. disease that is initially judged as unresectable may become amenable to surgical excision after a major response induced by imatinib therapy. Most centers recommend surgical resection for such patients because it is feared that residual GIST may develop secondary mutations that could result in clinical resistance to imatinib and progression of disease

23. sunitinib definitely improved the progression-free survival of patients following imatinib failure due to resistance or intolerance

24. Definitive expert surgery remains the mainstay of treatment for patients with localized, primary GIST

25. Adjuvant Therapy to Improve Outcomes for Patients with Resected Early Stage
The standard of care after complete surgical resection of GIST has therefore been observation alone