How are GISTs diagnosed?

Dr Daleen Geldenhuys explains the diagnosis process of gastrointestinal stromal tumours (GISTs) and how targeted therapy has made it a treatable cancer.

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Gastrointestinal stromal tumours likely originate from the interstitial cells of Cajal. These cells are the pacemaker cells of the muscle cells in the intestine. They regulate peristalsis (involuntary muscle movement that moves food through gastrointestinal tract) by forming the interface between the (autonomic) nerve connection from the brain to the bowel wall and the smooth muscle itself. GISTs are rare tumours and present 1 – 2% of gastrointestinal tract tumours.

Muscle cells in the intestine differs from skeletal muscle and its named smooth muscle and is located below the lining cells of the gastrointestinal tract and regulate peristalsis of the gut. Tumours of these cells arise below the lining of the GI tract.

History and examination of patient

To make a diagnosis, the history and examination of the patient is paramount.

Adult patients with GISTs commonly present with some of the following signs and symptoms:

• Occult bleeding from the stomach, the small or the large intestine; these are most patients. Occasionally these tumours are diagnosed as incidental findings during gastroscopy or colonoscopy for screening purposes.
• Abdominal pain or discomfort. They rarely present with an acute abdomen which implies possible perforation of the bowel or tumour rupture. The mass can cause bowel obstruction, mimicking colon cancer.
• An asymptomatic mass is rare but can be a presenting symptom. Early satiety and bloating may be the only symptoms.
• Hypothyroidism, secondary to normal thyroid hormone degradation by the tumour have been reported in large tumours and may be a rare presenting symptom.

The physical examination may reveal a mass if the tumour is large enough. Peritonitis (redness and swelling of the lining of abdomen) and bowel obstruction may be found but most of these tumours present without symptoms and spread outside the abdomen is rare.

There are familial syndromes in which more than one family member may have the disease. They may have other symptoms which may help identifying these patients earlier.

Special investigations

Imaging

Investigations include endoscopy, endoscopic ultrasound, CT scanning, and MRI especially when the tumour is in the rectum. The tumours have smooth contours and enhances brightly with intravenous contrast. Very large tumours may appear more complex due to necrosis or even bleeding into the tumour. The scan may also allow assessment of local invasion into adjacent structures. PET-CT may be useful for monitoring, rather than diagnosing, specifically if lymph node involvement is suspected.

Histology

A biopsy or excision biopsy is paramount to make the diagnosis and to determine the type of GIST and to exclude other diagnoses. The pathologist will confirm the diagnosis and will also give other genetic markers to predict response to the different oral therapies that are available for this tumour. The number of mitoses per high power field (in simple terms how many tumour cells are actively dividing) is important to determine the duration of therapy after the tumour is excised. The most prominent diagnostic marker is the universal overexpression of CD117 which is easily identified.

Treatment

These tumours are not responsive to chemotherapy and radiation and before the advent of targeted therapy, GISTs had a dismal prognosis.

Surgery

Excision of the tumour is vital for treatment and control of this tumour type. The tumour may be removed endoscopically if small enough or with open or laparoscopic robotic surgery.

Oral therapy

If the tumour is big, surgery may cause morbidity. It’s acceptable to first treat the tumour with oral therapy (neo-adjuvant treatment) to facilitate surgery with less morbidity.

After the tumour is removed, depending on the size of the tumour, its location, and the number of mitoses per high power field (as seen under a microscope), a decision is made regarding the risk of recurrence and to treat with oral medication to prevent the recurrence of the tumour.

If the tumour is multifocal (more than one) or there are intra-abdominal metastases, and surgery may not improve the outcome, oral therapy is acceptable. Patients can be treated successfully for many years with the available medication. The medication is directed to the specific mutations and have manageable side effects.

GISTs are no longer the untreatable threat it used to be. Treatment is successful in terms of quality and quantity of life.

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