Gastrointestinal Stromal Tumors (GISTs) – The Unique and Mysterious Tumors of the Gut

As we observe Sarcoma Awareness Month, it’s time to explore a lesser-known group of tumors called gastrointestinal stromal tumors (GISTs) that affect the gut. While rare, these tumors can have a significant impact on patients’ lives. Dr Ajesh Raj Saksena, a cancer surgeon at Apollo Cancer Center, Hyderabad, sheds light on their occurrence, symptoms, early detection, evaluation, and the treatment strategies that give hope to those facing these unique challenges.

Dr. Saksena explains, “GISTs are a rare subset of tumors that develop from specialized cells in the gastrointestinal tract known as the interstitial cells of Cajal, which help regulate intestinal motility. Though rare, these tumors can arise anywhere in the gut, including the stomach, small intestine, colon, and esophagus. While they were once elusive, advancements in diagnostic techniques have allowed us to better identify and understand them in recent years.”

Who is at Risk?

While the majority of GISTs appear to arise without a known cause, there are specific elements that might increase the risk:

Age and Gender: GISTs usually affect adults, with most diagnoses occurring between the ages of 50 and 70 years. It is important to remember that these tumors can emerge at any age, and there appears to be a slight male predominance in their occurrence.

Genetic Mutations: Specific genetic mutations, such as those found in the c-kit gene (CD117) and PDGFRA genes, may play a pivotal role in the development of these tumors in about 85-90% of cases. These mutations trigger abnormal cell growth and division, leading to the development of these tumors. More recently, other uncommon contributory pathways have also been identified which are associated with deficiencies in the succinate dehydrogenase complex, alterations in the NF1-gene and BRAF gene.

Family History: In a small percentage of cases, individuals with a family history of GISTs or related conditions, such as Neurofibromatosis Type 1 (NF1) or familial GIST syndrome, may be at an increased risk.

Dr. Saksena emphasizes, “It is crucial to keep in mind that GISTs can develop at any age, and although very rare, we have observed cases even in children and younger individuals. These tumors are driven by mutations in various exons i.e. specific regions within a gene that contains the coding sequence of DNA, of the c-kit and/or PDGFR genes. These mutations not only influence the prognosis but also present an opportunity for targeted treatment approaches.”

Clinical Symptoms – The “warnings” not to be ignored

GISTs often remain silent in their early stages, making them difficult to detect. Dr. Saksena shares, “In the beginning, GISTs may not cause noticeable symptoms. This lack of specific warning signs poses a challenge in their early diagnosis. They may be slow-growing indolent tumors to aggressive malignant cancers that can invade neighboring organs, metastasize to the liver, and recur within the abdomen.”

As GISTs grow, they can lead to various symptoms based on their location and size. Common signs may include persistent abdominal pain, gastrointestinal bleeding resulting in black, tarry stools (melena), and palpable abdominal masses during physical examination. In some cases, patients may experience anemia, nausea, vomiting, or even obstruction of the gastrointestinal tract.

Moreover, the obstructive signs and symptoms of GISTs can be site-specific. For example, an esophageal GIST can cause dysphagia or difficulty swallowing, while a colorectal GIST may lead to constipation. In some cases, a duodenal GIST might result in vomiting or jaundice. Understanding these site-specific symptoms is crucial in the early identification and management of GISTs.

Early detection is vital in effectively managing GISTs. Timely evaluation and a high index of suspicion play a crucial role in identifying these abnormalities. Additionally, individuals with a family history of GISTs or other sarcomas should be vigilant and seek comprehensive screening. Among the main prognostic factors in GIST patients are the tumor’s size, location, and the mitotic rate.

How do we evaluate?

Various imaging studies like ultrasonography, contrast CT scans, and MRI can now help visualize GISTs and provide essential information about their location and size.

Endoscopy, both upper and lower, allows us to directly visualize and assess the tumor. Typically GISTs are suspected when there is a well-defined mass arising from under the mucosal lining of the gut.

An endoscopic ultrasound (EUS) can be useful to clearly define the layer of origin, define the extent of the lesion, differentiate from other lesions which may mimic these tumors and take guided biopsies when required, avoiding a potential spillage of the tumor. Sometimes, further evaluation with a PET scan may be required to evaluate the spread of the disease or assess response to therapy.

A Comprehensive Approach to GIST Treatment

In addressing GISTs, a multifaceted and coordinated approach to treatment is essential. Dr. Saksena emphasizes, “Surgery remains the primary treatment for localized GISTs. The specific location from where these tumors arise and size of the tumor determine the type and extent of surgery required, which may include wedge resection, partial gastrectomy, or small bowel resection. Utmost care is taken to ensure complete removal of the tumors without any spillage, as this significantly impacts the treatment outcome.”

In the realm of GIST treatment, a remarkable breakthrough has been achieved with targeted therapies known as tyrosine kinase inhibitors (TKIs). These therapies are designed to target specific molecular abnormalities within GIST cells. Imatinib, a tablet initially used for treating blood cancers, has demonstrated remarkable effectiveness in managing GISTs. TKIs may be administered as an adjuvant treatment after the complete removal of the tumor, or as a neoadjuvant therapy to downstage tumors before surgery. Moreover, these medications are employed to manage non-resectable tumors, metastatic disease, and even recurrent scenarios. Notably, significant progress has been made with the development of second-line and third-line therapies, offering promising outcomes for patients facing GIST challenges.

Regular follow-ups and imaging studies play a crucial role in monitoring treatment response and detecting any recurrence or metastasis. Dr. Saksena concludes, “By raising awareness about GISTs during this Sarcoma Awareness Month, we can promote early detection, better treatment, and improved outcomes for those facing these unique challenges. Together, we can conquer the these tumors and achieve the best results”

Dr Ajesh Raj Saksena

Consultant Surgical Oncologist

Apollo Cancer Center,

Apollo Hospital, Jubilee hills, Hyderabad drajeshraj@gmail.com | www.drajeshraj.com