What are Gastrointestinal Stromal Tumors (GISTs)?
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are believed to originate from the interstitial cells of Cajal or related stem cells. They can occur anywhere along the gastrointestinal tract but are most commonly found in the stomach and small intestine.
Histological Features of GISTs
Histologically, GISTs are characterized by spindle cell, epithelioid, or mixed cell types. Spindle cell GISTs consist of elongated cells with eosinophilic cytoplasm and tapering ends, often arranged in fascicles. Epithelioid GISTs, on the other hand, have rounder cells with abundant eosinophilic or clear cytoplasm.How are GISTs Identified?
A definitive diagnosis of GISTs is often made using
immunohistochemistry. The majority of GISTs express
CD117 (c-KIT), a protein which is a part of the receptor tyrosine kinase family. In addition,
DOG1 (Discovered on GIST-1) is another marker that is often positive in GISTs and is helpful in the diagnostic process.
Molecular Pathogenesis
Most GISTs are driven by mutations in the KIT or PDGFRA genes. These mutations lead to the constitutive activation of the receptor tyrosine kinases, resulting in uncontrolled cell proliferation and survival. This forms the basis for targeted therapy using tyrosine kinase inhibitors like imatinib.Clinical Presentation
Patients with GISTs may present with a variety of symptoms depending on the size and location of the tumor. Common symptoms include abdominal pain, gastrointestinal bleeding, and, in some cases, a palpable mass. Smaller tumors might be asymptomatic and found incidentally during imaging studies or endoscopy.Histological Grading and Prognosis
The prognosis of GISTs can be estimated based on histological grading, which includes factors such as tumor size, mitotic index, and location. Tumors with a high mitotic rate or large size are associated with a poorer prognosis. Additionally, GISTs located in the small intestine generally have a worse prognosis compared to gastric GISTs.Treatment Approaches
The primary treatment for localized GISTs is surgical resection. For metastatic or unresectable GISTs, targeted therapy with tyrosine kinase inhibitors is the mainstay of treatment. Imatinib is the first-line treatment, with other options like sunitinib and regorafenib available for cases resistant to imatinib.Conclusion
Gastrointestinal stromal tumors are a unique entity within the spectrum of gastrointestinal tumors. Histological examination, combined with immunohistochemical staining and molecular testing, is crucial for accurate diagnosis and effective treatment planning. Advances in targeted therapy have significantly improved outcomes for patients with this once challenging-to-treat malignancy.
