What Is Gastrointestinal Stromal Tumor

Overview

Gastrointestinal Stromal Tumor (GIST) is a rare tumour that occurs in the gastrointestinal tract (GI tract); this type of tumour can arise from the interstitial cells of Cajal that are electrical pacemakers and mediators of neurotransmission in the GI tract. Also, GIST is a type of soft tissue sarcoma.¹ It is most commonly present in the stomach with a prevalence between 50% and 60% and small intestine with 30% - 35%, but GIST may also present in the colon, rectum, oesophagus, mesentery, and omentum with a percentage of 15%. The prevalence of GISTs was estimated to be 15/100,000 people, and they form 0.1%-3.0% of gastrointestinal malignant tumours, which commonly occur in middle-aged and elderly populations (mostly 60-70 years) but infrequently in younger generations.^2,3 The symptoms of GIST can vary from case to case; while some cases may have pain, bleeding, or just feeling unwell, other cases may have no symptoms. While GIST is an uncommon cancer, it is essential to be aware of its symptoms and consult a healthcare practitioner if any concerns arise. Early detection and appropriate treatment can significantly improve the chances of successful treatment and better outcomes for GIST patients. 

Causes of GIST

The causes of gastrointestinal stromal tumours (GIST) are not completely understood. However, recent research found that the majority of GISTs are associated with primary genetic mutations in specific genes, such as the PDGFRA gene and the KIT gene. The mutations in these genes lead to aberrant activation of the cellular signalling pathways, which are responsible for cell growth regulation, division and apoptosis in the GI tract; these mutations lead to uncontrolled cell proliferation and tumour growth which results in GISTs development.⁴ Several studies have shown that approximately 5-10% of GIST cases have mutations in the PDGFRA gene, while approximately 85-95% of GIST cases have mutations in the KIT gene.⁵

Moreover, there are secondary genetic alterations which could have a role in the GIST progression and development, such as alterations in tumour suppression genes and other signalling pathways.

In addition, most of the GISTs are considered sporadic cancer, which means the gene mutations that cause GIST are not inherited. However, a small percentage of gastrointestinal stromal tumour cases could be associated with inherited genetic syndromes. For example, people with neurofibromatosis type 1 (NF1) may have an increased risk of GIST growth, particularly GISTs located in the small intestine.6 Another uncommon genetic syndrome associated with GIST development, along with other stomach tumours, adrenal glands and lungs, is called the Carney triad.⁷

Signs and symptoms of GIST

The signs and symptoms of GIST can vary depending on the tumour size, growth rate and location. In some cases of the Gist's early stages, symptoms could be unnoticeable. However, certain signs and symptoms may appear as the tumour spreads or grows to other parts of the body.⁸

• Common signs and symptoms of GIST:
  • Gastrointestinal bleeding: GISTs may cause bleeding in the GI tract, which could result in vomiting blood or blood in the stool.
  • Anaemia: chronic gastrointestinal bleeding may lead to a gradual decrease in RBCs (red blood cells), resulting in anaemia; because of that, the patient may have weakness, shortness of breath and general fatigue.
  • Abdominal pain or discomfort: Several GIST patients have suffered from abdominal pain or discomfort, which can be intermittent or persistent. The pain may range from mild to severe, and in some cases, it might be localized or expanded throughout the abdomen.
  • Feeling full after eating small amounts: In some cases with GIST, the patient may have a reduction in the amount of food intake due to a sensation of fullness and inability to eat normal-sized meals.
  • Unexplained weight loss: Some individuals with GIST may experience unintentional weight loss, even without any change in physical activity or diet.
  • Palpable mass or lump: in some GIST cases, patients may experience a large GIST, which can be felt as a lump or a mass in the abdominal area during physical examination.^8,9

It is worth mentioning that these signs and symptoms are not specific to gastrointestinal stromal tumours, and they might be linked with other gastrointestinal conditions. Hence, it is important to consult a healthcare practitioner if any of these signs and symptoms are present. 

Management and treatment for GIST

There are several factors which affect the management and treatment of gastrointestinal stromal tumour (GIST), such as:

• The size and location of the tumour,
• How quickly the tumour is spreading,
• The presence of certain gene mutations.

The primary treatments for gastrointestinal stromal tumours may include surgery, targeted therapies and adjuvant therapy in some cases.

• Surgery: the main goal of surgery is to cut out the whole tumour along with a margin of the surrounding healthy tissue to ensure a complete ablation.¹⁰ Minimally invasive surgery can be utilized in GIST cases where the tumour is small and well-defined, such as laparoscopic surgery.¹¹ However, open surgery might be required for larger and more complex tumours.
• Targeted Therapies: GISTs are associated with primary genetic mutations in specific genes, such as mutations in KIT or PDGFRA genes. The main mechanism of GISTs targeted therapies is to block the abnormal signalling pathways that are activated by the mutated genes, leading to tumor growth inhibition.  These targeted therapies are known as tyrosine kinase inhibitors (TKIs)¹² Currently, the most commonly used TKIs for gastrointestinal stromal tumours are Sunitinib, Imatinib and Regorafenib.⁹ These are oral medications which require regular monitoring and dose adjustments.
• Adjuvant Therapy: Adjuvant therapy is more recommended after tumour excision, especially for GIST individuals who have a high risk of recurrence. Targeted therapies such as imatinib can improve the overall outcomes and reduce the risk of cancer recurrence.¹³ The choice and duration of this therapy are determined by the treating oncologist, and it is dependent on several risk factors.
• Multidisciplinary Approach: A multidisciplinary team, including surgeons, pathologists, medical oncologists, and radiation oncologists, is often involved in the management and treatment of GIST cancer. These healthcare professionals cooperate in developing a personalized treatment plan based on the GIST patient’s overall health status and the characteristics of the tumour.

It is important for GIST patients to undergo follow-up visits to monitor treatment response, detect any progression and recurrence of the disease and assess potential side effects. This follow-up care may include physical examinations, blood tests and imaging tests to evaluate the patient’s condition.

Diagnosis

The diagnosis of GIST includes a combination of pathological examination, clinical evaluation, imaging investigation and molecular testing. The following methods are usually used to diagnose and confirm the presence of a gastrointestinal stromal tumour and to define its characteristics.

1. Clinical assessment: This is the initial step to diagnose GIST; the healthcare provider often requests a detailed medical history and examines the patient’s symptoms. Also, the healthcare provider will perform a physical examination to assess any abdominal masses or lumps.
2. Imaging studies: imaging techniques play an essential function in the diagnosis and staging of GIST, such as computed tomography (CT) scan, magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS).^14,15
3. Pathological Examination: this method is usually necessary to confirm GIST diagnosis. The following techniques are mostly used:
   • Biopsy: a biopsy involves the extraction of small tissues from the tumour to determine the presence of GIST. The main common method is endoscopic biopsy.¹⁶
   • Immunohistochemical Staining: this process can be used to distinguish the diagnosis of GIST and confirm it from other types of cancer by analyzing the expression of specific proteins like CD117 b(KIT) and CD34 in the tumour tissue.¹⁷

4. Molecular Testing: This method is used to examine specific genetic mutations which are associated with GIST cancer, such as mutations in KIT or PDGFRA genes. By performing polymerase chain reaction (PCR) or sequencing methods.¹⁸

FAQs

How can I prevent GIST?

While the exact causes of GIST are unclear, there are no specific methods to prevent it. However, according to the American Cancer Society, adopting a healthy lifestyle, such as maintaining a balanced diet, avoiding smoking and excessive alcohol consumption, and exercising regularly, can promote overall health and potentially decrease the risk of different cancers, including GIST. In addition to routine health checkups, awareness of family history and genetics consulting.¹⁹

How common is GIST?

A gastrointestinal stromal tumour (GIST) is an uncommon type of cancer, accounting for approximately 0.1% to 3% of all gastrointestinal tumours. It is more common in adults between 50 and 70 years, with an incidence of 10 to 20 GISTS per million people/year.

Who is at risk of GIST?

Although most GIST cases may occur sporadically without a clear cause, studies have shown certain factors can increase the risk. For example, mutations in the KIT or PDGFRA genes, a family history of GIST, a family history of Carney triad or neurofibromatosis type 1 (NF1), being male and people of older age (50-70 years).

When should I see a doctor?

If you notice any persistent or concerning symptoms such as abdominal pain, unexplained weight loss, or blood in the stool, notice a new mass or lump in the abdomen. Also, if you have a family history of GIST or related syndromes, it is essential to consult a doctor and seek medical attention for screening and evaluation. Early medical diagnosis and treatment are crucial for controlling and improving outcomes in GIST.

Summary

Gastrointestinal Stromal tumour (GIST) is a rare type of cancer which can start and develop in the digestive system, mainly in the stomach and intestines. GISTs occur when special cells called interstitial cells of Cajal (ICCs) grow abnormally and form a tumour. The exact cause of GIST is not completely understood, but many factors may increase the risk, like older age, gender, a family history of GIST and certain genetic mutations.

GIST can cause various signs and symptoms depending on the tumour’s location and size. These may include abdominal pain, bleeding from the digestive tract (resulting in visible blood in the stool), unexplained weight loss, difficulty in swallowing, or a noticeable mass in the abdomen.

To diagnose GIST, oncologists use a combination of clinical assessment, imaging studies like CT scans and MRI, biopsy and pathological examination and molecular testing to examine specific genetic mutations and confirm the presence of GIST.

Management and treatment of GIST usually involve surgical removal of the tumour. In some cases where cancer has spread, or surgery is not feasible, targeted therapy with tyrosine kinase inhibitors (TKIs) medications may be used to slow down the growth of the tumour. Regular follow-up visits with healthcare professionals are essential to detect any changes or signs of recurrence. While the gastrointestinal stromal tumour is an uncommon cancer, it is important to be aware of its signs and symptoms and consult a healthcare provider if any concerns arise. Early detection and treatment can improve outcomes for people with GIST.