Appendiceal GIST: report of an exceptional case and review of the literature

Gastro-intestinal stromal tumors (GISTs) of the appendix are a rare entity. To date, only eight cases has been described in the literature, most of which have been of the benign type. We report a new case of an appendiceal GIST in a 75-year-old man. The tumor was discovered when the patient presented with acute appendiceacal peritonitis. Preoperative diagnosis of appendiceal GIST was rarely done as tumors were usually associated with appendicitis-like symptoms.


Introduction
Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal neoplasms of the gastrointestinal (GI) tract.
GISTs occur most commonly in the stomach (60%) and the small bowel (30%). Appendiceal GISTs are extremely rare making up approximately 0.1% of all cases, with eight cases reported in the literature thus far, seven of these cases were benign. Only in one reported case, the malignant nature of the lesion was confirmed.

Discussion
Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA [1,2] They are located typically in the submucosa of the stomach and the small and large intestines, although cases arising in the esophagus, greater omentum, and mesenterial adipose tissue have been described [3].
Appendiceal GISTs are extremely rare making up approximately 0.1% of all cases [4], with eight cases reported in the literature thus far; seven of these cases were benign and measuring less that 3 cm in diameter [5]. Only in one reported case, the malignant nature of the lesion was confirmed [6].
Based on the previously reported 8 cases and our case, patients with appendiceal GISTs have a mean age of 67 years (range, 56-78 years) with a remarkable predilection for men (3.5:1).
Three tumors were associated with appendicitis-like symptoms in the absence of histologic evidence of acute appendicitis, suggesting that the symptoms were caused by the tumor [5,7,8]. Three other tumors were found incidentally during surgery for other diseases or at autopsy [5,7]. One other tumor was associated with acute appendicitis [7], and with a peri-appendiceal abscess for the last case [6]. For our case, the tumor was discovered when the patient presented with an acute peritonitis.
Consistent with the high incidence of associated other malignancies in GIST patients in general [4], 4 of 9 patients with appendiceal GISTs were affected by other cancers : 3 had carcinomas [5,7], and 1 had a synchronous malignant gastric GIST [7]. One patient had neurofibromatosis type 2 [8]. The locations were as follows: mid portion (n = 5), tip (n = 3), and proximal part (n = 1). Three tumors were extramural, and 1 was pedunculated. Their mean size was 33.5 mm (range, 2.5-200 mm). Seven of the eight previously reported appendiceal GISTs were spindled, mitotically inactive lesions corresponding to prognostic groups 1 (n = 6) and 2 (n = 1) according to Miettinen and Lasota [4] and were at very low risk (n = 6) and low risk (n = 1) according to the National Institutes of Health consensus criteria [9]. For one case, the size of the tumor, number Page number not for citation purposes 3 of mitosis and locally invasive surgical findings clearly confirm the malignant nature of the lesion [6].
In our case, six previous cases examined by immunohistochemistry showed a uniform coexpression of CD117 and CD34. None was positive for desmin, smooth muscle actin, or S-100. None of 3 patients with follow-up (mean, 49 months)had evidence of progressive disease.
The main problem with our patient was whether to consider the tumor as ruptured, as the patient was in general peritonitis, or not.
In patients with tumoral rupture, it would be acceptable to administer imatinib for more than 3 years. On the other hand, our patient had general peritonitis due to a perforation of the apex of the appendix and the tumor was located in the mid portion, so that, adjuvant therapy was not administrated.

Conclusion
Gastro-intestinal stromal tumors (GISTs) of the appendix are a rare entity. To date, only eight previous cases have been described in the literature, seven of which have been of the benign type.
Preoperative diagnosis was rarely done as tumors were usually associated with appendicitis-like symptoms.