Gastrointestinal Stromal Tumors

Definition of Gastrointestinal Stromal Tumor the most common mesenchymal

malignancy of (GI) tractthe diagnostic criteria for GIST

remained controversial and somewhat confusing

Pathology Terms that Encompass the Spectrum of Gastrointestinal Stromal Tumors Gastrointestinal stromal tumor

Leiomyoblastoma

Gastrointestinal leiomyosarcoma

Gastrointestinal autonomic nerve tumor

Gastrointestinal pacemaker cell tumor

Plexosarcoma

Gastrointestinal neurofibrosarcoma

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

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

Clinical Considerationsadults 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.

abdominal painabdominal mass, nausea, vomiting, anorexiaweight loss. acute hemorrhage

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

Diagnostic Evaluation CTMRIupper GI endoscopyUltrasonographically enhanced

endoscopy

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

DDXsoft tissue sarcomasEwing's sarcoma and angiosarcomasmall cell lung cancers, melanomas desmoid tumorsseminomas, ovarian carcinomas, mastocytomas, neuroblastomas, adenoid cystic carcinomas,subsets of lymphoma and acute myeloid

leukemia.

Metastatic

Or un resecta

ble

h risk I risk low risk Very low risk

اندازه و اندازه هرمیتوز

از بیشتربا 5یا 10

متیوز یا متوسط

زیاد

از 3کمتر 5تا 2بین از 2کمترسانتیمتر

میزان میتوز

متوسط کم کم

some contribution to prognosisOther 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

Diagnostic Imaging PETFDG-PET imaging can detect

lesions at least 1 cm

CT MRI

Management of Metastatic, Unresectable, or Recurrent Gastrointestinal Stromal TumorCht: P-glycoprotein (the product

of the multidrug resistance-1 [MDR-1] gene) and the multidrug resistance protein-1 MRP1

RT: bleeding , pain

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

FDA approval of imatinib for dermatofibrosarcoma protuberans

toxicitiesnausea, vomiting, and severe edema,diarrhea myalgia or musculoskeletal pain skin rashes headache MyelotoxicityCardiotoxicityhemorrhagic events tachyphylaxis

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

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

The optimal duration of imatinibcontinued dosing with imatinib as

long as the disease is not progressive

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

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

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

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