Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor (GIST) is a rare mesenchymal neoplasm of the gastrointestinal tract arising from interstitial cells of Cajal, often driven by activating mutations in KIT or PDGFRA genes.

Definition

Gastrointestinal stromal tumor (GIST) is a rare mesenchymal neoplasm of the gastrointestinal tract arising from interstitial cells of Cajal, often driven by activating mutations in KIT or PDGFRA genes.

Epidemiology

Accounts for <1% of all gastrointestinal malignancies
Most common mesenchymal tumor of the GI tract
Median age at diagnosis: 60–65 years
Slight male predominance
Stomach is most common site (60%), followed by small intestine (30%), colon/rectum (5%), esophagus (<5%)

Etiology

Somatic activating mutations in KIT (~75–80%) or PDGFRA (~5–10%) genes
Rare familial GIST syndromes due to germline mutations
NF1-associated GISTs in patients with neurofibromatosis type 1
Environmental or lifestyle risk factors not clearly established

Pathophysiology

Mutations in KIT or PDGFRA lead to constitutive activation of tyrosine kinase signaling
Promotes uncontrolled proliferation and survival of interstitial cells of Cajal
Tumor may grow intraluminally, extraluminally, or within the bowel wall
Potential for local invasion, hemorrhage, or obstruction
Metastasis usually occurs to liver and peritoneum; lymph node involvement is rare