Extragastrointestinal Stromal Tumor Mimicking Appendicitis: A Case Study

Introduction

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms primarily found in the gastrointestinal (GI) tract. GISTs originate from the interstitial cells of Cajal, which are specialized regulators of GI peristalsis. Proto-oncogene mutations, notably in KIT or PDGFRA, drive tumorigenesis via tyrosine-kinase pathways. Most GISTs occur in the stomach (60–70%) or small intestine (20–30%), with rare instances in the esophagus, colon, and rectum [1]. Men exhibit a higher GIST incidence (35.6%) than women (0.9%) [2]. The spindle cell variant of GIST presents cells arranged in compact fascicles and swirling patterns. These cells exhibit a characteristic pale eosinophilic fibrillary cytoplasm, along with oval-shaped nuclei and blurred cell boundaries [3]. Notably, gastric spindle cell GISTs frequently exhibit prominent perinuclear vacuolization, a distinctive diagnostic hallmark previously associated with smooth muscle tumors [4]. Prompt and accurate diagnosis is crucial for effective management, utilizing imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), biopsy, and histopathological assessment with immunohistochemical staining for CD117 and CD34.

In this case report, we present a 75-year-old man who experienced right lower quadrant pain and ultimately received a diagnosis of a colonic mesentery GIST. The association between GIST and appendicitis-like symptoms poses a diagnostic challenge; these symptoms can arise from secondary inflammation caused by luminal obstruction from the tumor [5].

Case Report

INVESTIGATIONS:

Blood test results showed microcytic hypochromic anemia and a normal leukocytic count. An abdominal CT scan showed a heterogeneous density mass in the right lower quadrant measuring up to 11.3×9.2 cm. The mass abutted the right aspect of the distended urinary bladder and was within proximity to the ileal loops (Figure 1A, 1B).

The appendix was visualized in the right lower quadrant and appeared dilated and fluid-filled, with wall thickening. The maximum diameter was 1.4 cm. The findings were concerning for acute appendicitis (Figure 1C).

SURGERY AND PATHOLOGY:

The patient was taken for exploratory laparotomy on an elective basis. During the surgical procedure, the abdomen was explored, and adhesions were carefully taken down using electrocautery. A palpable mass, located at the mesentery of distal ileum, was encasing part of the small bowel, which required resection and primary anastomosis using a linear stapler. Owing to the location of the mass, we elected to proceed with right hemicolectomy with primary anastomosis. The resected specimen, including the small bowel mass and hemicolectomy segment, is shown in Figure 2, highlighting its macroscopic dimensions (11.3×9.2 cm).

The pathological findings were positive for high-risk GIST spindle cell type, forming a 19-cm mass centered in the colonic mesentery, with at least 50 mitoses per 5 mm². There were uninvolved colonic and ileal margins; however, the small intestine mesenteric margin was positively involved, and there were 20 uninvolved lymph nodes (0/20). The stage was pT4N0.

Discussion

An E-GIST is a subtype of GIST that develops outside of the GI tract, with no connections to the intestinal walls or serosal surfaces of GI organs. GISTs are very rare, with an annual incidence of only 10 to 20 per million, and of this amount, only 10% occur as E-GISTs [6]. E-GISTs are most commonly present in the abdominal wall, lesser omentum, pancreas, scrotum, mesentery, and retroperitoneum [7]. In the present case, the mass was centered in the colonic mesentery, without involvement of the ileal and colonic margins.

The clinical presentation of E-GISTs can vary greatly, and symptoms rely heavily on the location and size of the mass [8]. Although patients often present asymptomatically, most patients present with abdominal pain or distension. In the present case, the patient presented with right iliac fossa abdominal pain, generalized fatigue, and dysuria. While abdominal pain is expected for a mesenteric E-GIST, fatigue and dysuria are not [8].

Non-contrast MRI and contrast-enhanced CT are both efficient techniques for detecting GISTs in a patient [9]. In a study by Zhou et al, the specificity and sensitivity of these imaging techniques for the detection and surveillance of GISTs were examined; for non-contrast MRI, these were 91% and 83%, respectively, and for contrast-enhanced CT, they were 84% and 76%. When a patient presents with symptoms typical of E-GIST, or a physical examination is positive for a significant abdominal mass, imaging tests are warranted [10]. Tumors can be discovered during investigation for another medical condition, with 20% of GISTs being asymptomatic and found incidentally [8]. This case was an example of incidental discovery. The patient’s initial symptom of right lower abdominal pain suggested an acute presentation of appendicitis. This prompted an abdominal and pelvic CT scan with contrast, revealing a dilated appendix with a maximum diameter of 1.4 cm, filled with fluid and exhibiting wall thickening, further supporting the appendicitis diagnosis. Incidentally, a large mass was seen in the right lower quadrant near the ileal loops, and a differential diagnosis of GIST was developed, leading to further investigation. The CT results also showed the mass abutting the bladder, providing a reason behind the patient’s unusual dysuria.

E-GIST and GIST originate from interstitial cells of Cajal, the pacemaker cells of the GI tract, which induce peristalsis [11]. Mutations of the c-KIT gene and, occasionally, platelet-derived growth factor receptor alpha (PDGFRA) can cause GIST and E-GIST [12]. The c-Kit gene is responsible for the KIT protein, a receptor tyrosine kinase present on interstitial cells of Cajal [13]. GIST and E-GIST can have similar mutations; however, in a study in which 18 tumors were tested, it was found that E-GIST had the KIT mutation in 27.8% of cases and the PDGFRA mutation in 38.9% of cases. In contrast, GIST was seen to have the KIT mutation in 75% of cases and the PDGFRA mutation in 8% to 10% of cases [8].

CT and MRI are essential ways to screen and detect E-GISTs, but biopsy is the method for definitive diagnosis [14]. E-GISTs are known to have specific markers, such as C-kit (CD117), DOG-1, and PKC-0 [15]. In a study in which immunohistochemical features of 48 E-GISTs were analyzed, other tumor markers were also expressed. These included the expression of CD117 (100%), CD34 (50%), neuron-specific enolase (44%), SMA (26%), desmin (4%), and S-100 protein (4%) [12]. In our case, the tumor was positive for markers CD117, DOG1, Bcl-2, D2-40, and WT1.

Treatment is usually based on staging. Mesenteric E-GIST has been seen to be more aggressive [16]. In most cases, surgical resection is the best option for localized masses [17]. Benefits from chemotherapy and radiotherapy have shown limited success [18]. Most GISTs are shown to have cKIT mutations. This gene is responsible for the KIT protein, a tyrosine kinase receptor.

Imatinib mesylate, a tyrosine kinase receptor inhibitor, is used as adjunct therapy after surgical resection of a GIST. In the case of our patient, the mesenteric E-GIST (pT4N0) was surgically resected, and imatinib, a tyrosine kinase receptor inhibitor, was recommended as adjunct therapy after surgical resection for the tumor that was estimated as high risk. Any GIST that is greater than 10.0 cm in size is considered high risk, regardless of mitotic count [19]. For this reason, a mitotic count was not conducted. The results indicated that our patient was at a high risk of reoccurrence. A risk stratification of gastrointestinal stromal tumors (GISTs) is critical to guide follow-up and management (Table 1). Furthermore, high-risk patients treated with adjuvant imatinib require careful monitoring, including imaging studies to detect recurrence (Table 2) [19].

Conclusions

This case highlights the significant challenges in diagnosing extramural GISTs, particularly when their clinical presentation closely mimics other abdominal conditions. Accurate diagnosis requires a multifaceted approach integrating advanced imaging, meticulous histopathological evaluation, and precise immunohistochemical analysis. The importance of a multidisciplinary strategy cannot be overstated, as it is essential for guiding effective postoperative care, minimizing the risk of recurrence, and ultimately improving patient outcomes.