Jejunal gastrointestinal stromal tumors mimicking arteriovenous malformation: A review of the literature

INTRODUCTION

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of mesenchymal origin and represent the most common non-epithelial tumors of the gastrointestinal tract.¹ The reported age-adjusted incidence ranges from 0.55-0.78 per 100,000 population, with notable geographical variation.^2,3 GISTs are most frequently diagnosed between the 50s and 70s of a person’s life and show no significant sex predilection.⁴

Clinical outcomes depend on tumor size, mitotic activity, anatomical location, and disease stage at diagnosis. Patients with localized disease demonstrate excellent long-term survival, whereas prognosis worsens in locally advanced and metastatic settings.⁵

Most GISTs are incidentally detected, as they often remain asymptomatic. Chronic gastrointestinal bleeding is a common presentation, if symptomatic. Acute, massive hemorrhage is rare and may lead to diagnostic confusion, particularly when radiological features resemble vascular anomalies such as arteriovenous malformations (AVMs).^6-11 We report a case of jejunal GIST presenting with severe gastrointestinal bleeding and imaging findings mimicking an AVM, highlighting the diagnostic challenges and management considerations.

CASE REPORT

A 45-year-old male, a non-smoker and a vegetable vendor by occupation, presented to the emergency department with bleeding per rectum for seven days. The initial presentation involved melena for two days, followed by passage of fresh and altered blood with clots. A similar self-limiting episode had occurred one year earlier. There was no history of abdominal pain, vomiting, or weight loss.

On examination, the patient was hypotensive with marked pallor and generalized edema. Symptoms of dyspnea, palpitations, and extreme fatigue were suggestive of congestive cardiac failure secondary to severe anemia. Digital rectal examination revealed altered blood and clots without an identifiable source.

Laboratory evaluation confirmed profound anemia with a hemoglobin level of 2.9 g/dL. Other parameters were within normal limits. Following resuscitation and blood transfusion, upper gastrointestinal endoscopy and colonoscopy failed to identify the bleeding source.

Contrast-enhanced computed tomography angiography demonstrated a 3.9×3.1×3.3 cm hyperenhancing lesion in the mid-jejunum with tortuous arterial feeders and early venous drainage, raising suspicion of a jejunal AVM [Figure 1]. Given the diagnostic uncertainty and potential risks of embolization, surgical intervention was planned.

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Figure 1: Reconstructed angiographic contrast-enhanced computed tomography image showing a hyper-enhancing mass in the jejunum with features consistent with those of an arteriovenous malformations (AVM) (arrow).

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Diagnostic laparoscopy revealed a 4×3×2.5 cm submucosal, firm mass was seen on the antimesenteric border of the jejunum with prominent feeder vessels draining it [Figure 2]. A firm jejunal mass with a prominent vascular supply was found intraoperatively. A mucosal ulcer overlying the lesion was identified as the bleeding site [Figure 3]. However, no active bleeding was present. Resection of the affected bowel segment and anastomosis of the bowel was performed using intestinal staplers.

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Figure 2: A firm jejunal mass with prominent vascular supply was found intraoperatively.

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Figure 3: The mucosal surface of the resected specimen revealed a mucosal ulcer, which was evidently the bleeding site.

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The postoperative period was uneventful, and the patient was discharged on postoperative Day 5.

The histopathological examination showed a 4×3×2.5 cm firm, exophytic mass lesion with attached jejunal segment. The cut section of the tumor had a gray-white appearance with focal areas of hemorrhage. No areas of necrosis or cystic changes were noted. Resected ends of the jejunum were free of the tumor. Microscopy showed the presence of spindle-shaped cells in fascicles with focal areas of calcification [Figures 4a-c].

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Figure 4a: Microscopic sections revealed spindle-shaped cells arranged in fascicles. Hematoxylin and eosin staining (40x).

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Figure 4b: With focal areas of calcification. Hematoxylin and eosin staining (40x).

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Figure 4c: With focal areas of calcification. Hematoxylin and eosin staining (40x).

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Areas of focally dilated vessels were seen, which were representative of the hypervascularity present on CT imaging. Mitotic rate of >3-4/5 hpf was observed. discovered on gastrointestinal stromal tumors (DOG 1) and smooth muscle actin were positive [Figures 5a and b].

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Figure 5a: Immunohistochemical staining revealed positivity for discovered on gastrointestinal stromal tumors (DOG 1),100x magnification.

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Figure 5b: Immunohistochemical staining revealed positivity for smooth muscle actin, 100x magnification.

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A diagnosis of low-risk GIST according to the CAP protocol was made. No histological evidence of arteriovenous malformation could be found.

Patient is still following up in the outpatient department every three months and was found to be doing well. The patient was not considered for chemotherapy, being a low-grade tumor.

DISCUSSION

GISts may arise anywhere along the gastrointestinal tract, most commonly in the stomach, followed by the small intestine.¹² These tumors originate from the interstitial cells of Cajal, which play a critical role in regulating gastrointestinal motility.^13,14 Molecularly, most GISTs harbor activating mutations in the c-KIT pathway.¹⁵ c-KIT, DOG 1 (Discovered on GIST-1), CD 117 (Cluster of Differentiation 117), and CD 34 (Cluster of Differentiation 34) are used as important immunohistochemical markers for making the diagnosis of GIST.¹⁶

The identification of CD117 (c-KIT) expression represents a pivotal diagnostic feature of gastrointestinal stromal tumors, allowing reliable distinction from other spindle-cell neoplasms of the gastrointestinal tract, including leiomyomas and leiomyosarcomas, which are typically CD117-negative.¹⁵ GISTs are believed to arise from the interstitial cells of Cajal, which physiologically express c-KIT, a type III receptor tyrosine kinase. These cells function as pacemakers of the gastrointestinal tract by generating slow electrical waves that regulate peristalsis.^13,14

On immunohistochemistry, approximately 95% of GISTs demonstrate positivity for KIT (CD117), while CD34 expression is observed in nearly 70% of cases.^13,17,18 In addition to KIT alterations, GISTs may harbor mutations involving platelet-derived growth factor receptor alpha (PDGFRA), components of the succinate dehydrogenase (SDH) complex, or the BRAF gene; mutations in the RAS family are uncommon.^17,18 Anatomically, GISTs most frequently involve the stomach (approximately 60%) and small intestine (20–30%), but may arise at any site along the gastrointestinal tract and, rarely, in extra-gastrointestinal locations such as the omentum, mesentery, or peritoneum.^17-19 These extra-gastrointestinal tumors are thought to originate from ectopic interstitial cells of Cajal displaced during embryogenesis.

From a molecular perspective, approximately 75% of GISTs harbor KIT mutations, most commonly involving exon 11, followed by exon 9, with less frequent involvement of exons 13, 14, 17, and 18.^20,21 PDGFRA mutations account for about 10% of cases, predominantly affecting exon 18; the D842V substitution is associated with resistance to imatinib, whereas non-D842V variants generally retain sensitivity.^22,23 Approximately 10–15% of GISTs are wild-type for both KIT and PDGFRA.^24,25 Among these, SDH-deficient tumors constitute a significant subset, resulting from SDHx mutations or epigenetic silencing of the SDHC promoter.^24,25 Less frequently, alterations involving BRAF (V600E), NF1, or rare gene fusions such as ETV6-NTRK3, FGFR1 rearrangements, and FGF4 amplification have been reported.^24-26

The following table summarizing the two major differential diagnosis, that is Jejunal AVM and GIST [Table 1]. To date, only a limited number of cases have been reported worldwide describing jejunal GISTs radiologically mimicking arteriovenous malformations. These cases are summarized in Table 2.^6–11 Most patients presented with overt gastrointestinal bleeding, and the lesions were relatively small at diagnosis, likely contributing to early clinical detection.

In several reports, angiographic findings fulfilled established imaging criteria for AVM; however, histopathological examination failed to demonstrate true vascular malformations. Although, the imaging findings were suggestive of an intrinsic hypervascular nature of the tumor. Surgical resection was the definitive treatment in all reported cases, with favorable outcomes and no documented recurrences during follow-up.

Complete surgical resection with negative margins remains the cornerstone of management for localized GISTs. Minimally invasive approaches are increasingly favored in appropriately selected patients. Tyrosine kinase inhibitors, particularly imatinib, are reserved for unresectable, recurrent, or metastatic disease and as adjuvant therapy in high-risk tumors.^27-29

The first TKI approved by the Food and Drug Administration was imatinib mesylate, a first-line treatment for unresectable or metastatic GISTs and used as an adjuvant or neoadjuvant therapy. This was followed by sunitinib, a second-line TKI and finally regorafenib, a third-line TKI [28]. Adjuvant imatinib therapy should be considered a standard treatment in all patients who underwent resection of a primary GIST and have a significant risk of recurrence.²⁹

All the above reported cases were managed by surgical resection. Only one of these, used laparoscopic methods and the rest proceeded with exploratory laparotomies. No recurrences were reported in any of the cases. Most of the lesions were less than 5cm at presentation causing early detection and management as compared to the median size of detection (5-8cm).

Despite advances in targeted therapy, recurrence occurs in a significant proportion of patients, underscoring the importance of risk-adapted surveillance strategies.^30-33 In low-risk tumors, such as in the present case, surgery alone is usually sufficient and long-term outcomes are favorable.

Postoperative surveillance strategies in GIST patients depend on the estimated risk of recurrence. Individuals with very low-risk tumors may not require intensive follow-up, although the risk of recurrence is not entirely absent. In patients classified as low risk, contrast-enhanced computed tomography is generally recommended at six-month intervals for up to five years.

Patients with intermediate- or high-risk disease require closer monitoring, particularly during the first three years following treatment, when the likelihood of recurrence is greatest. Functional imaging modalities such as PET-CT are especially useful in patients receiving tyrosine kinase inhibitors, as they provide early assessment of treatment response and detection of resistant or recurrent disease.^31-34

Although gastrointestinal stromal tumors are relatively uncommon, they should be considered an important differential diagnosis in patients presenting with acute, massive gastrointestinal bleeding. The potential for hypervascular GISTs to mimic arteriovenous malformations on cross-sectional imaging represents a significant diagnostic challenge and underscores the importance of correlating radiological findings with clinical and pathological features. This case adds to the limited existing literature on this rare presentation and emphasizes the need for heightened diagnostic awareness.

CONCLUSION

In conclusion, GISTs, although uncommon, should be recognized as an important differential diagnosis in patients presenting with acute gastrointestinal bleeding, particularly when imaging suggests vascular abnormalities such as arteriovenous malformations. Their hyper vascular nature can closely mimic AVMs, creating significant diagnostic challenges and highlighting the need for careful correlation of clinical, radiological, histopathological, and immunohistochemical findings. Definitive diagnosis relies on surgical exploration and pathological confirmation, with complete surgical resection remaining the cornerstone of treatment for localized disease. Early recognition and timely intervention are essential for achieving favourable outcomes, while risk-adapted surveillance remains crucial to monitor recurrence and guide long-term management.