Epidemiology and Pathophysiology
Although GISTs are the most common mesenchymal tumors of the gastrointestinal tract, they are still significantly less frequent than epithelial neoplasms or lymphomas. The primary patient demographic consists of adults over 50 years of age.
The tumors originate from stem cells of the muscularis mucosae (muscularis propria)—the so-called interstitial cells of Cajal, which normally function as the pacemakers of the intestine.
The pathogenesis of the disease is based on a genetic defect: approximately 95% of cases show overexpression of KIT receptors (CD117 marker). This is the product of the KIT proto-oncogene, and its excess leads to a pathological increase in tyrosine kinase activity. As a result, a process of continuous cellular hyperproliferation is triggered.
Historical Note: Before the discovery of specific immunohistochemical markers, these tumors were often mistaken for ordinary smooth muscle neoplasms (leiomyomas) because their morphological picture under standard light microscopy is very similar.
Clinical Presentation and Malignancy Potential
GIST symptoms directly depend on the size of the mass and its anatomical location. The most common initial clinical manifestation is gastrointestinal bleeding, whereas bowel obstruction is significantly less frequent.
Regarding prognosis, about 20–25% of gastric tumors behave in a clinically malignant manner. It is important to note that gastric GISTs generally have a less aggressive course compared to small intestine tumors (so-called enteric GISTs).
Key Predictors of Malignancy:
- Maximum size of the neoplasm.
- Mitotic activity of the cells.
If the tumor metastasizes, the liver and abdominal cavity structures are most frequently targeted. Involvement of regional lymph nodes or the appearance of lung metastases is completely uncharacteristic of GISTs and occurs in extremely rare cases.
The primary treatment method remains complete surgical resection. If the process has progressed to the metastatic stage, the drug of choice is the selective tyrosine kinase inhibitor imatinib mesylate (imatinib mesylate).
Associated Syndromes and Differential Diagnosis
In the vast majority of cases, GISTs occur sporadically. However, about 5% of tumors develop as part of genetic syndromes. In descending order of frequency, these include:
- Neurofibromatosis type 1 (NF1).
- Carney triad (Carney triad).
- Familial GIST syndrome (familial GIST syndrome).
In addition to GISTs, non-stromal mesenchymal tumors can also occur in the gastrointestinal tract. Their spectrum is completely identical to soft tissue neoplasms of other locations. This group includes lipomas and liposarcomas, true leiomyomas and leiomyosarcomas, desmoid tumors, and peripheral nerve sheath tumors (including schwannomas).
Diagnostic imaging (CT and MRI)
The radiological appearance of GISTs largely depends on the size of the mass.
Small Tumors:
- Often incidental findings during CT, MRI, endoscopic examinations, or surgeries.
- Present as solid nodules with subserosal, intramural, or, less commonly, polypoid intraluminal growth patterns.
- The overlying mucosa remains intact.
- On post-contrast tomograms (CT and MRI), they show homogeneous contrast enhancement.
Large Tumors:
- Appear as exophytic masses with heterogeneous (non-uniform) contrast enhancement.
- The structural heterogeneity is due to secondary changes: cyst formation, necrosis zones, hemorrhages, ulceration, and the appearance of cavities (cavitary changes).
- Specific CT Sign: If the luminal margin (facing the lumen) of the tumor ulcerates, accumulations of gas and oral contrast agent can be visualized within the mass itself.
According to CT data, gastric tumors can demonstrate various growth patterns: exophytic, endophytic, intramural, or subserosal. Furthermore, the presence of a large necrotic node with a fully exophytic growth type is considered a reliable diagnostic sign of GIST.
Liver Metastases: Usually hypervascular in nature. On unenhanced MRI scans, their features are nonspecific (low signal on T1-weighted images and high on T2-weighted images). However, with contrast enhancement on CT and MRI, they demonstrate intense enhancement in the late arterial phase followed by rapid and almost complete washout (washout) in the portal venous phase.
Briefly: answers to topical questions
What factors are considered when stratifying the malignancy risk of GISTs?
Four main factors are taken into account when stratifying the risk of progression and malignancy in gastrointestinal stromal tumors.
These include:
- Tumor size — measured in centimeters.
- Mitotic index (MI) — the number of mitoses per 50 high-power fields.
- Primary tumor location — stomach, small intestine, duodenum, or rectum.
- Capsular rupture — the presence of damage to the tumor capsule.
What are the endoscopic and endosonographic features of GISTs?
Endoscopically, GISTs may appear as solid subserosal, intramural, or, less frequently, polypoid intraluminal masses with an intact mucosa.
In the esophagus on endoscopic ultrasound, GISTs appear as submucosal masses originating from the muscularis mucosae (muscularis mucosa) or muscularis propria (muscularis propria). Without a biopsy, they are difficult to differentiate from leiomyomas.
What targeted drugs are used for GISTs in case of imatinib resistance?
In the event of secondary resistance to imatinib or its intolerance, sequential targeted therapy with other drugs is used.
The following inhibitors are used:
- Sunitinib — prescribed as second-line therapy upon failure of imatinib treatment.
- Regorafenib — used as third-line therapy upon disease progression during sunitinib treatment.
Adherence to this algorithm for changing medications is a strict quality criterion for the treatment of metastatic forms.
The rule of three "C"s for GISTs: Cajal cells (origin), Bleeding (common symptom), KIT/CD117 (receptor mutation).
Class and exam questions
Why were GISTs often confused with leiomyomas in the past?
Under routine light microscopy, stromal tumors look virtually identical to smooth muscle tumors. Accurate diagnosis only became possible after the discovery and clinical implementation of the CD117 (KIT) marker.
Which imaging feature is considered specific for large ulcerated GISTs?
The presence of gas and oral contrast medium within the bulk of an exophytic tumor. This occurs when the edge of the mass facing the intestinal lumen is destroyed (ulcerated).
How do liver metastases of GIST behave on contrast-enhanced CT/MRI?
They are hypervascular: they intensively accumulate contrast in the late arterial phase and demonstrate rapid washout in the portal venous phase.
What else to study on this topic
- Assessment of mitotic activity as a key predictor of malignancy
- Carney triad: components of the syndrome and association with GISTs
- Mechanism of action of imatinib mesylate in the treatment of metastatic GISTs
- Differential diagnosis of GIST and gastric schwannomas on CT
- Imaging features of non-stromal mesenchymal tumors of the GI tract
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