Sunday, March 21, 2010

Gastrointestinal Stromal Tumors (GIST)

- Can arise from any mesenchymal component of gastric wall (hence previous designation of leiomyoma/leimyosarcoma)
- 3% of all gastric malignancies
- 50% of GIST in the stomach
- Carney triad: nonhereditary syndrome in young females (children) - gastric GIST, paraganglioma, pulmonary chondroma.
- increased incidence of GIST in pts with NF1
- Main route of metastasis is hematologic.  Lymphatic dissemination rare (<10%) therefore extensive lymphadenectomy not indicated
- presentation will largely depend on whether mass enalrges intraluminally or extraluminally

Metastases:
- 50% present with mets
- metastases can present as multiple serosal nodules throughout the peritoneal cavity or nodules in the liver. Extra-abdominal mets are rare.

Diagnosis:
- needle biopsy is not indicated, risks seeding or tumor rupture: soft and fragile tumor
- ? if unresectible then perhaps consider biopsy to justify upfront imatinib ?make the lesion resectable
- low risk metastases: <5cm, <5 mitoses/50 HPF

Pathology:
- Firm gray-white masses.
- often have a pseudocapsule that separates tumor from normal smooth muscle
- 80% have gain of function mutation of tyrosine kinase c-KIT, 8% have mutation that activates tyrosine kinase PDGFRA
- common stem cell - interstitial cells of Cajal

Adjunctive Therapy:
- NOT radiosensitive
- traditional chemo does not improve survival
- Imatinib: small molecule inhibitor of c-kit receptor

Survival:
- 5 year survival is 42% with complete resection
- survival drops to 9% with incomplete resection (?pre-Gleevec era)

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