Gastrointestinal stromal tumors

Discussion

Gastrointestinal stromal tumors can arise at any age; however, more than 80% are reported in individuals older than 50 years, with the average age of 63 years. The reason for the younger age group in our study (median: 54 years) compared to the reported data was the fact that we have a younger population in general. The most frequent tumor location was the stomach in all reported studies. In a recent systematic review including all published population-based studies on GISTs, the most common primary tumor location was the stomach in 55.6% of 9747 reported GISTs, followed by, in descending frequency, the small bowel in 31.8%, the colorectal area in 6%, and the esophagus in 0.7% of cases.7 Other locations were reported in 5.5% of cases. Similarly, in our study, the frequency of the anatomical location of GISTs in descending order was the stomach (63.8%), small bowel (25%), colon (5.6%), esophagus (2.8%) and rectum (2.8%) (Table 1).

The reported data regarding specific symptoms in various studies were dependent on the categories and definitions used. Among the most common symptoms reported, abdominal pain, gastrointestinal bleeding and intestinal obstruction were the most common; however, several other nonspecific complaints were also observed. We observed similar findings in clinical presentations with abdominal pain (33.3%) and GI bleeding (30.5%) being the most common mode of presentation. However, abdominal mass was the reason for presentation in 25% of the cases. Lower GI bleeding presented in 4 patients due to colorectal GIST in three patients and small bowel GIST in one patient (Table 1).

According to the NCCN taskforce guidelines for GISTs, tumor biopsy for suspected GISTs should only be considered in the case of suspicion of alternative diagnoses or when neoadjuvant is contemplated. However, if the lesion is accessible through an endoscopic approach, then this mode of biopsy is preferred to the percutaneous approach.8 By contrast, if the lesion is small and surgically resectable, or if prior biopsy carries a serious risk for complication, then surgical resection without preceding biopsy is acceptable.

In general, gastric GISTs have more favorable prognosis at similar stages compared to that of other anatomical locations. Gastric GISTs equal to or less than five cm in size with five mitoses per 50 HPFs or less have a reported low risk for metastasis, whereas those originating from the small bowel (irrespective of size or mitoses) or gastric GISTs with more than five cm diameter more than 5 mitoses per 50 HPFs have moderate to high risk for metastasis.

Data from studies reporting NIH risk groups showed that very low-risk GIST groups were the least frequent (15%), while low-, intermediate- and high-risk groups accounted for 30%, 22%, and 33% of the cases.5,6 Similarly, in our study, 5 cases (13.9%) were in the low-risk group, 17 cases (47.2%) were in the intermediate-risk group and 14 cases (38.9%) were in the high-risk group. There were no very low-risk cases in our study (Table 2).

Most reported GISTs were local disease when first detected, and overt metastases were found in approximately 10%-20% of cases.6 Most reported metastatic GISTs were found in the abdominal cavity and the liver, while other rare sites such as bones have occurred. In our study, 10 cases (28%) were stage IV at the time of their presentation. This represented a higher incidence than the published data and reflected the need for a high index of suspicion and awareness among physicians and patients in our area (Table 3).

Hirota9 demonstrated mutations in the c-Kit proto-oncogene in GISTs associated with the expression of Kit protein (also known as CD117). Currently, the diagnosis of GISTs is usually established by demonstrating positive staining for both CD 117 and CD34. However, equally important is the demonstration of negative results for S-100, desmin, CK and LCA to rule out other differential diagnoses.10

A comparison of various studies to the present one is depicted in Table 4. Our study showed the prevalence of positive and negative receptors including c-kit and CD34 and other IHC expression compared to other populations.11-14

A cure is possible in patients with surgically margin-negative resection in resectable GISTs. Therefore, it is important to establish risk-stratification schemes to aid in estimating recurrence-free survival and to reduce the complications of unnecessary overtreatment with adjuvant systemic chemotherapy. Hence, low-risk patients have a favorable outcome by complete surgical resection with no need for adjuvant chemotherapy. Targeted therapy with tyrosine kinase inhibitors has revolutionized the outcome of completely resected tumors, resulting in prolonged responses in patients who had advanced disease.15-17 Due to the higher incidence of advanced stages in our cases, with only 13.9% of patients classified as low risk and the majority as either intermediate or high risk, surgery was achievable in 31 (86.1%) of the patients. However, in only 16 (44.5%) of our patients, surgery alone was curative, while 15 (41.6%) patients were treated surgically followed by adjuvant chemotherapy. Five (13.9%) patients were not candidates for surgical resection because of advanced disease. In those patients were the surgical intervention is not possible, the targeted therapy poses a survival-benefit therapeutic option were offered in four of our patients.17 All our cases did not pose any diagnostic dilemma hence DOG1 receptor detection was not done as the importance of this receptor in c-KIT negative specimens. Therefore, it was considered cost-ineffective.18-20 The only report in the literature regarding GISTs emanating from our region did not report the prevalence of all receptors, giving the present study a unique status as a reference for comparison.21

In conclusion, GISTs are a rare type of tumor in the Eastern Province of Saudi Arabia. Unfortunately, no accurate epidemiological data are available. Although there are no specific trends, nevertheless, GISTs are more commonly seen in middle-aged women and in younger populations compared to other countries. Furthermore, we observed more advanced tumor stage in our patients population. Finally, GIST characteristics in our community demonstrate similarities to the reported international data with respect to clinical and pathological characteristics, however, our study shows some unique findings that can serve as a reference for clinicians in our area.