Gastrointestinal Stromal Tumors - Clinical Presentation, Diagnosis, and Prognosis

What Is a Gastrointestinal Stromal Tumor (GIST)?

A gastrointestinal stromal tumor is a type of cancer that occurs in the digestive tract. It belongs to a group of cancers known as sarcomas. Sarcomas are cancerous lesions that develop in the body's bone or soft tissues. This differentiates them from carcinomas (which arise from the lining of organs like the lung, breast, prostate, etc.), lymphomas (which arise from lymph nodes), and from leukemias (which arise from immune cells in the bone marrow).

A GIST starts in the cells called the intestinal cells of Cajal (ICCs). The ICCs, also called pacemaker cells, are normal nerve cells that coordinate the movement of food and liquids in the digestive tract. Recently, cells called telocytes have also been known to undergo mutations leading to a GIST formation. Telocytes are also intestinal cells that play an important role in cell-to-cell signaling.

This shows the heterogeneous nature of the GISTs; they have different origins but are similar due to their location (all of them being present in the digestive tract), the pattern of spread, drug sensitivity, resistance, and prognosis.

What Causes GISTs?

• Sometimes, the genes present in the ICCs and the telocytes (either the KIT gene or the PDGFRA gene) get mutated, leading to a GIST.

• A mutation is a random alteration in the genetic material; some of these alterations make cells grow out of control leading to a lump or mass known as a tumor. The mutation that causes the GISTs is not inherited from one generation to another.

• The GIST results from a mutation in the KIT gene or the PDGFRA gene. The KIT gene produces an enzyme called tyrosine kinase. This enzyme is responsible for sending growth and survival signals to the cells. When a mutation occurs in this KIT gene, it will produce an unnecessary amount of tyrosine kinase enzyme, which will trigger the cells to divide continuously, leading to a mass of cells.

• The second cause of GIST is the mutation in the PDGFRA gene. This gene produces the necessary proteins which are needed for the cells to grow. When it gets mutated, it produces the excess protein on which the cells feed. This leads to an abnormal increase in the size of the cells. The uncommon increase in the number and size of the cells in the digestive tract constitutes a GIST.

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What Are the Signs and Symptoms of a GIST?

GISTs have a wide range of subjective symptoms, the common ones being nausea, feeling full after eating a small amount (early satiety), bloating, and weight loss. The objective signs of a GIST are anemia and a lump in the abdomen. The specific signs and symptoms of the GISTs depend on the tumor's location, size, and growth pattern.

The most common site for a GIST is the stomach; the associated symptoms are-

• Pain.

• Palpable mass.

• Gastrointestinal (GI) bleeding will lead to anemia that will cause symptoms below.

1. Fatigue.

2. Paleness and lightheadedness.

• Fever.

• Weight loss.

• Abscess and urinary tract infections.

If the GIST is located in the esophagus (which is also a part of the digestive tract), then along with the above symptoms, it will cause difficulty in swallowing (dysphagia). The symptoms will be different if the GIST has metastasized into a different area of the body. Metastasis is when the cancer cells which have originated from one place migrate to a different organ, thereby spreading cancer. GISTs are mostly benign, meaning they stay in the location where they originated, but in recent times due to the advancement in technology, it has been observed that GISTs have the potential to spread to organs like the lungs and bone. If they spread, the symptoms will be similar to that of bone or lung cancer, and the only way to identify them is through laboratory investigations.

What Are the Investigations Done GISTs?

The patient's health history, symptoms, physical examination, and family history are necessary for the initial diagnosis. If the clinician suspects a GIST, one or more of the below-mentioned tests will be requested to confirm the diagnosis.

• Endoscopy- An endoscope is a thin fiber-optic instrument with a camera and light attached to it. The clinician will pass it down the patient's throat, enabling them to see and locate the GIST inside the stomach.

• Imaging Tests- Either a computed tomographic (CT) scan or a magnetic resonance imaging (MRI) can be done as part of the imaging tests to locate and note the spread of the GIST.

• Biopsy- It is the gold standard for diagnosing GIST. Small pieces of intestinal tissue are collected either through an endoscope or a needle and sent for histopathological studies. If the sample is positive for KIT (or CD117) or PDGFRA protein, it is indicative of a GIST.

If a GIST is confirmed, the clinician will request further tests to determine the cancer stage; this is necessary to plan the treatment.

How Are GISTs Treated?

Treatment depends on the rumor's location, size, and metastatic nature. Surgery is preferred in GISTs confined to one site, and tumors that have also metastasized will need targeted medical therapy along with surgery.

• Surgery- The goal of the surgery is to remove the entire tumor. An open approach is made if the size is more than five centimeters, whereas a laparoscopic approach is made for tumors less than 5 cm. Both procedures are done under general anesthesia; if it is an open approach, the surgeon will make one large abdominal incision, whereas the laparoscopic approach involves multiple small incisions through which a laparoscope and special surgical instruments will be introduced to resect the tumor. Once the tumors are excised, the incisions will be closed with absorbable sutures.

• Targeted Medical Therapy- At times, a large tumor will make it impossible to remove it through surgery; the doctor will treat this with the help of targeted medical therapy, which shrinks the tumor, followed by surgical excision.

The targeted medical therapy includes chemotherapeutic drugs approved by the food and drug administration (FDA). A few FDA-approved chemotherapeutic drugs are Imatinib, Sunitinib, Regorafenib, and Avapritinib.

Alternative treatments include bland-embolization, radio-embolization, and chemo-embolization; they work by cutting off the blood supply to the tumors. A new treatment called immunotherapy is currently under trial for GISTs; it works on the principle of strengthening the body’s natural immune system, which will identify and kill cancer cells. The clinician decides the type of treatment after careful evaluation.

What Are the Side Effects of GIST Treatment?

The side effects depend on the type of treatment performed. Surgery is usually well-tolerated with common complications like bleeding and infection that can be eliminated with efficient post-operative care.

Side effects of target medical therapy include anemia, edema, fatigue, nausea, pleuritic pain, diarrhea, granulocytopenia, and rash. This can be managed with adjuvant therapy prescribed by the clinician.

Conclusion:

Diagnosis and treatment of GISTs is a multidisciplinary approach. The primary care provider is important in the initial workup and treatment compliance. An endoscopist is essential to visualize the tumor; the histopathologist confirms the diagnosis, an oncologist conducts the therapy, and a radiologist monitors the prognosis. Performing all these steps with efficient coordination will improve treatment outcomes and enhance the patient's quality of life.