What are the diagnostic criteria for Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

The diagnostic criteria for Gastrointestinal Stromal Tumor (GIST) rely on a combination of clinical evaluation, imaging studies, and pathological confirmation, with a definitive diagnosis requiring histopathological examination and immunohistochemistry, as well as molecular testing for KIT and PDGFRA gene mutations, as recommended by the British Sarcoma Group clinical practice guidelines 1.

Diagnostic Approach

The diagnosis of GIST typically starts with clinical evaluation, where patients may present with symptoms such as abdominal pain, gastrointestinal bleeding, or a palpable mass, although some GISTs are asymptomatic and discovered incidentally 1.

• Diagnostic imaging, particularly contrast-enhanced CT scans, is used to visualize the tumor.
• Endoscopy and endoscopic ultrasound can provide detailed imaging and enable tissue sampling for histopathological examination.

Pathological Confirmation

Definitive diagnosis requires histopathological examination of tissue obtained through endoscopic biopsy or surgical resection, with GISTs typically showing spindle cell or epithelioid morphology 1.

• Immunohistochemistry is crucial, with most GISTs expressing CD117 (c-KIT) and/or DOG1, although about 5% of GISTs are CD117 immunonegative and about 5% are DOG1 immunonegative 1.
• Molecular testing for KIT and PDGFRA gene mutations helps confirm diagnosis and guides treatment decisions, as these mutations drive GIST pathogenesis and determine response to targeted therapies like imatinib 1.

Risk Assessment

Complete evaluation should include tumor size, mitotic rate, and location to assess risk of aggressive behavior and inform treatment planning, with larger tumors and higher mitotic rates indicating a higher risk of malignancy 1.

• The mitotic count has prognostic value and is more accurate and reproducible when expressed as the number of mitoses in a total area of 5 mm2, which is therefore recommended 1.

From the Research

Diagnostic Criteria for Gastrointestinal Stromal Tumor (GIST)

The diagnostic criteria for GIST are based on several factors, including:

• Histopathological examination: GISTs are characterized by mutations in the c-Kit gene, as well as other mutations such as those in the platelet-derived growth factor receptor alpha (PDGFRA) gene 2, 3.
• Immunohistochemistry: The majority of GISTs show expression of the membrane receptor protein CD117 with a tyrosine kinase activity c-kit, and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1 4, 5, 6.
• Tumor location and size: GISTs can occur at any level of the digestive tract, but the stomach and small intestine are the most common locations 2, 4, 5.
• Mitotic rate: The prognosis of GIST depends on its size, mitotic activity in 50 high power fields and mucosal infiltration 5.

Classification of GIST

GISTs can be classified into three main types based on histopathology:

• Spindle cell type
• Epithelioid type
• Mixed type 2, 3.

Diagnostic Tools

Several diagnostic tools can be used to diagnose GIST, including:

• Computed tomography (CT) scan: To identify the tumor and its location 4.
• Endoscopy: To visualize the tumor and take biopsies 5.
• Fine-needle aspiration biopsy (FNAB): To diagnose GIST and allow for preoperative therapy with tyrosine kinase inhibitors (TKI) 6.
• Positron emission tomography: A useful and promising diagnostic procedure 5.
• Immunohistochemical staining for DOG-1, C-Kit (CD117) and protein kinase C theta (PKCθ): To confirm the diagnosis of GIST 6.