In a retrospective study of 200 GIST cases, typical clinical manifestations of malignancy included liver metastases and/or dissemination within the abdominal cavity. Lymph node involvement and spread to the lungs or other extra-abdominal sites was unusual. Advanced disease may be associated with metastases to distant sites, including lung and bone. Brain metastases are rare.
GIST should be included in the differential diagnosis of any intra-abdominal nonepithelial malignancy. Diagnostic interventions may include the following:
- Computed tomography (CT).
- Magnetic resonance imaging.
- Upper GI endoscopy.
Tests that may be useful in staging include the following:
- 18 FDG-PET (18 fluoro-deoxyglucose-positron emission tomography).
Endoscopic ultrasound with fine-needle aspiration biopsy is useful in the detection of GIST in the upper GI tract because most tumors arise below the mucosal layer and grow in an endophytic fashion.[12,13,14]
Because nodal metastasis is so rare at diagnosis (i.e., it is virtually unheard of for true GIST according to the AJCC Cancer Staging Manual), there is general agreement that nodal dissection is not needed.
Pathology and Molecular Genetics
Typically arising within the muscle wall of the GI tract, GIST range in size from less than 1 cm to more than 40 cm, with an average size of approximately 5 cm when diagnosed clinically. Small GIST may form solid subserosal, intramural, or, less frequently, polypoid intraluminal masses. Large tumors tend to form external masses attached to the outer aspect of the gut involving the muscular layers. GIST morphology is quite varied; the tumors are composed of the following:
- Spindle cells (70%).
- Epithelioid cells (20%).
- Mixed spindle and epithelioid cells (10%).
GIST encompass a broad continuum of histologic patterns, ranging from bland-appearing tumors with very low mitotic activity (often previously designated leiomyomas) to very aggressive-appearing patterns (previously often called leiomyosarcomas). They may originate from interstitial cells of Cajal (ICC) or their stem cell-like precursors, although this is not certain.[15,16]
The most commonly used marker for GIST is the CD117 antigen, a marker expressed by ICC. Approximately 95% of GISTs are positive for the CD117 antigen, an epitope of the KIT receptor tyrosine kinase.[2,9] However, CD117 immunohistochemistry is not specific for GIST, as weak reactivity occurs with other mesenchymal neoplasms; accordingly, morphologic examination and the use of other immunostains in difficult cases are indispensible. In addition, false-positive CD117 staining can occur if antigen retrieval techniques are used in the pathology laboratory to enhance marker expression. Because of a relatively broad morphologic spectrum, the differential diagnosis of GIST includes several mesenchymal, neural, and neuroendocrine neoplasms that occur in the abdomen including the following:
- Malignant peripheral-nerve sheath tumor.
- Solitary fibrous tumor.
- Inflammatory myofibroblastic tumor.
- Synovial sarcoma.
- Neuroendocrine tumors (carcinoid and islet cell).
- Gastric glomus tumor.
- Malignant mesothelioma.
- Sarcomatoid carcinoma.