Managing locally advanced GIST complicated by perforation: A case report and comprehensive review

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, frequently characterized by mutations in the KIT or PDGFRA genes. This case report details the complex clinical course of a 71-year-old female with a history of HIV and metastatic GIST presenting with acute abdominal symptoms indicative of perforated viscus. Initial imaging revealed a massive pneumoperitoneum and a large abdominal mass, necessitating immediate surgical intervention. The patient underwent multiple surgeries, including bowel resections and colostomy creation, to address the extensive tumor burden and complications. Postoperatively, she required intensive care management, including mechanical ventilation, vasopressor support, and hemodialysis for acute kidney injury. Pathological examination confirmed metastatic GIST with extensive mesenteric and omental involvement. Immunohistochemical staining was positive for CD117 (c-KIT) and DOG-1. Despite aggressive surgical and supportive measures, the patient's condition highlighted the significant challenges in managing advanced GIST with perforation. This case highlights the importance of a multidisciplinary approach, integrating surgical, medical, and intensive care to optimize outcomes. The prognosis of GIST varies widely, with localized tumors having favorable outcomes following resection, while metastatic cases often face a poorer prognosis despite advances in targeted therapies. This case exemplifies the critical need for personalized treatment plans and ongoing research to improve the management and prognosis of GIST patients.

Introduction

Gastrointestinal stromal tumors (GISTs) represent the most common type of mesenchymal neoplasms found within the gastrointestinal tract, accounting for approximately 1%-2% of all gastrointestinal malignancies [1]. These tumors originate from the interstitial cells of Cajal, which function as pacemaker cells for gut motility [2]. Most GISTs harbor activating mutations in the KIT gene (75%-80%) or, less frequently, in the PDGFRA gene (5%-10%), leading to constitutive activation of receptor tyrosine kinases that drive tumor growth and proliferation [1].

GISTs can manifest anywhere along the gastrointestinal tract, with the stomach and small intestine being the most common sites of origin [3]. Clinical presentations vary widely and can include nonspecific symptoms such as abdominal pain, gastrointestinal bleeding, and obstructive phenomena. Some GISTs are discovered incidentally during imaging or endoscopic procedures conducted for other reasons [4].

The diagnosis of GIST involves a combination of imaging, endoscopy, and histopathological examination [5]. Contrast-enhanced computed tomography (CT) scans are typically the imaging modality of choice, providing detailed information about the tumor's size, location, and potential metastases [6]. Endoscopic ultrasound (EUS) with fine-needle aspiration can be used to obtain tissue samples for definitive diagnosis [7]. Histologically, GISTs are characterized by CD117 (c-KIT) and DOG-1 expression, which are key markers for confirming the diagnosis [8].

Management of GIST has been revolutionized by introducing tyrosine kinase inhibitors (TKIs) such as imatinib, which target the KIT and PDGFRA mutations [1]. For localized GISTs, surgical resection with negative margins remains the primary treatment approach [6,9]. Adjuvant therapy with imatinib is recommended for patients with a high risk of recurrence [10]. Imatinib is the first-line treatment in cases where the tumor is unresectable or metastatic, significantly improving progression-free and overall survival [7,10]. Other TKIs, such as sunitinib and regorafenib, are used for patients who develop resistance to imatinib [11,12].

Despite these advancements, the management of GIST, especially in advanced stages, poses significant challenges. Factors such as tumor size, location, and mutation type influence treatment outcomes [1,7]. Additionally, complications like tumor rupture or perforation require prompt and multidisciplinary interventions to manage acute symptoms and stabilize the patient [13,14]. Ongoing research aims to understand the molecular mechanisms of GIST better and develop more effective treatment strategies, including novel targeted therapies and combination approaches.

Case presentation

A 71-year-old female with a significant medical history, including HIV on antiretroviral therapy Bictegravir, Emtricitabine and Tenofovir Rlafenamide (Biktarvy), obesity, hypertension (HTN), hyperlipidemia (HLD), and a prior diagnosis of gastrointestinal stromal tumor (GIST) with liver metastases, presented to the emergency department with worsening abdominal distention, abdominal pain, fever, diarrhea, and shortness of breath. She had been recently hospitalized for perforated diverticulitis and had ongoing symptoms since her discharge. Upon arrival, her vital signs indicated a temperature of 97.5°F, heart rate of 120 beats per minute, respiratory rate of 36 breaths per minute, SpO2 of 89%, and blood pressure of 161/73 mmHg.

Initial diagnostic workup included a chest X-ray (CXR), which revealed a massive pneumoperitoneum consistent with a perforated hollow viscus (See Fig. 1). A subsequent CT scan of the chest, abdomen, and pelvis without IV contrast confirmed a large amount of free intraperitoneal air throughout the abdomen and pelvis, indicative of bowel perforation (See Fig. 2). Additionally, the CT scan identified a low-attenuation lesion between the superior aspect of the right kidney and the liver measuring 86 × 42 × 62 mm, suspicious for malignancy, and a large, calcified uterine mass measuring 10 × 8 × 8 cm. A smaller mass associated with the small bowel or mesentery and dilatation of the small bowel were also noted (See Fig. 3).

Fig. 1.

(CXR, frontal): The frontal chest X-ray reveals a massive pneumoperitoneum, as indicated by free air under the diaphragm (highlighted by the red arrow), consistent with a perforated hollow viscus. This finding is a critical indicator of gastrointestinal perforation and requires urgent medical intervention.

Fig. 2.

(CT chest, abdomen, and pelvis without IV contrast): The CT scan demonstrates a large amount of free intraperitoneal air distributed throughout the abdomen and pelvis (indicated by the red arrow), consistent with bowel perforation. Additionally, there is a low-attenuation lesion between the right kidney's superior aspect and the liver, measuring 86 × 42 × 62 mm, which is suspicious for malignancy (highlighted by the blue arrow).

Fig. 3.

(CT chest, abdomen, and pelvis without IV contrast): The CT scan reveals a small bowel or mesentery mass, accompanied by small bowel dilatation (outlined by the red box). This suggests the presence of a significant obstructive or infiltrative process involving the small intestine, which warrants further investigation and management.

Laboratory findings on presentation included a sodium level of 134 mEq/L, creatinine level of 4.23 mg/dL, lactate level of 2.9 mmol/L, white blood cell count of 10.5×10^9/L, hemoglobin level of 9.4 g/dL, procalcitonin level of 29.76 ng/mL, lipase level of 85 U/L, and arterial blood gas results showing a pH of 7.295 and HCO3 of 19 mEq/L.

The patient underwent an exploratory laparotomy, during which a small bowel resection and placement of an Abthera wound management system were performed. Intraoperative findings included a perforated small bowel, likely due to tumor involvement and a significant tumor burden in the mesentery and adjacent to the sigmoid colon. Postoperatively, the patient was transferred to the ICU for intensive monitoring and management.

The hospital course was complicated, necessitating multiple surgical interventions. She underwent further exploratory laparotomies with additional small bowel resections, sigmoid resection, abdominal washouts, ileo-colonic anastomosis revision, and colostomy creation. During this period, she required mechanical ventilation, pressor support for labile blood pressure, and extensive antibiotic therapy to manage ongoing infections. Her kidney function deteriorated, necessitating hemodialysis. Over several days, her condition gradually stabilized, and she was eventually extubated and transitioned to subacute rehabilitation.

Pathological examination confirmed the diagnosis of metastatic GIST with extensive involvement of the mesentery and omentum. The tumor exhibited strong immunohistochemical staining for CD117 (c-KIT) and DOG-1, which are characteristic markers for GIST. The resection margins were indeterminate due to the piecemeal nature of the tumor spread (See Fig. 4, Fig. 5, Fig. 6, Fig. 7).

Fig. 4.

(H&E stain, 400x magnification): The histology slide shows the tumor with characteristic spindled cells and a prominent mitotic figure (highlighted by the red circle). These features are typical of gastrointestinal stromal tumor (GIST), indicating an aggressive cellular proliferation pattern and confirming the diagnosis at the microscopic level.

Fig. 5.

(H&E stain, 400x magnification): The histology slide demonstrates areas of tumor necrosis (highlighted by the red square). This finding indicates cell death within the tumor, which is often associated with aggressive tumor behavior and can contribute to complications such as perforation.

Fig. 6.

(CD117 stain, 400x magnification): The histology slide shows positive CD117 staining of the tumor cells, confirming the gastrointestinal stromal tumor (GIST) diagnosis. The strong CD117 expression is a hallmark of GISTs, aiding in the definitive identification of this tumor type.

Fig. 7.

(DOG-1 stain, 400x magnification): The histology slide reveals strongly positive DOG-1 staining of the tumor cells, further confirming the gastrointestinal stromal tumor (GIST) diagnosis. The robust expression of DOG-1 is a key diagnostic marker, reinforcing the identification of this tumor type.

The patient's postoperative recovery was prolonged and complex, involving meticulous wound care, management of her colostomy, and ongoing dialysis. Her condition improved sufficiently to allow discharge home with follow-up in oncology for further management of her metastatic GIST. This case illustrates the intricate and multidisciplinary approach required to manage a patient with advanced GIST complicated by acute abdominal emergencies. It highlights the challenges in achieving optimal outcomes in such complex clinical scenarios.

Discussion and literature review

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, typically arising from the interstitial cells of Cajal [3]. These tumors are characterized by specific genetic mutations, primarily in the KIT gene (75%-80%) or PDGFRA gene (5%-10%), leading to constitutive activation of tyrosine kinase receptors and subsequent uncontrolled cell growth [15].

GISTs can present with various nonspecific symptoms, often challenging diagnoses. Common clinical manifestations include gastrointestinal bleeding, abdominal pain, and symptoms of bowel obstruction [5]. In some cases, like the one described, GISTs may be discovered incidentally during imaging for unrelated issues [7]. Our patient's presentation of acute abdomen with signs of perforation highlights the importance of considering GIST in the differential diagnosis of gastrointestinal emergencies, especially in patients with a known history of the disease [4].

Diagnostic evaluation typically includes imaging studies such as contrast-enhanced CT scans, which are crucial for assessing the tumor's size, location, and extent. Endoscopic ultrasound (EUS) with fine-needle aspiration may be used to obtain tissue samples for histological examination [2,16]. Immunohistochemical staining for markers such as CD117 (c-KIT) and DOG-1 is essential for confirming the diagnosis of GIST [17]. The presence of these markers was pivotal in diagnosing the metastatic GIST in our patient, highlighting the role of pathology in managing these tumors [15,17].

Surgery remains the primary treatment modality for localized GISTs, with the goal of achieving complete resection with negative margins [13]. Minimally invasive techniques, such as laparoscopic resection, are preferred when feasible due to their association with shorter recovery times and fewer complications [18,19]. However, managing metastatic or unresectable GISTs is more complex and requires a multimodal approach [20].

In our case, the patient underwent multiple surgical interventions, including exploratory laparotomies, bowel resections, and colostomy creation, to manage the acute complications of her metastatic disease. The extensive tumor burden and the perforation of the small bowel complicated her surgical management. Literature suggests that the presence of metastatic disease, particularly with complications like perforation, significantly impacts the surgical approach and prognosis.

Introducing tyrosine kinase inhibitors (TKIs) such as imatinib has revolutionized the treatment of GISTs, particularly for advanced and metastatic cases [21]. Imatinib targets the KIT and PDGFRA mutations, inhibiting tumor growth and improving survival rates. For patients with resectable tumors at high risk of recurrence, adjuvant therapy with imatinib for at least 3 years is recommended [22]. In cases where the tumor is unresectable or metastatic, imatinib serves as the first-line treatment, with other TKIs like sunitinib and regorafenib used for cases of resistance or intolerance [10,20].

Despite the efficacy of TKIs, resistance remains a significant challenge [23]. Secondary mutations in the KIT or PDGFRA genes can lead to treatment failure, necessitating alternative therapeutic strategies [24]. In our patient, the management of metastatic GIST would likely involve the initiation of TKI therapy postoperatively once her condition stabilized. The literature highlights the importance of molecular profiling in guiding treatment decisions and optimizing outcomes.

The complexity of GIST management, especially in cases involving extensive metastasis and complications like perforation, emphasizes the necessity of a multidisciplinary approach. This approach involves collaboration among surgeons, oncologists, radiologists, pathologists, and critical care specialists to provide comprehensive care. Our patient's course exemplifies the need for such a collaborative effort, as her management required multiple surgical procedures, intensive care, and plans for long-term oncological treatment.

Perforation is a rare but serious complication of GIST, often associated with a high risk of morbidity and mortality [25]. Perforated GISTs can present acutely with signs of an acute abdomen, including severe abdominal pain, distention, and signs of peritonitis [26]. This complication necessitates immediate surgical intervention to manage the perforation and prevent widespread infection and sepsis. The underlying mechanism typically involves tumor necrosis and subsequent weakening of the gastrointestinal wall, leading to rupture [27]. In the context of metastatic GIST, as seen in our patient, the surgical approach is further complicated by the extensive tumor burden and the presence of multiple metastatic sites [22]. Literature indicates that patients with perforated GISTs often have a worse prognosis due to the acute nature of the complication and the advanced stage of disease at presentation [22,26]. Effective management requires prompt surgical intervention, aggressive supportive care, and subsequent systemic therapy to address residual disease [19].

The prognosis of GIST varies significantly depending on factors such as tumor size, mitotic rate, location, and the presence of metastases [14]. Localized GISTs that are completely resected with negative margins generally have a favorable prognosis, with 5-year survival rates exceeding 80% when treated with surgery alone [6]. However, the presence of metastatic disease, as in our patient, markedly worsens the prognosis. The advent of TKIs, particularly imatinib, has improved survival outcomes for patients with advanced or metastatic GISTs, offering a median survival of approximately 5 years, which is significantly better than historical outcomes [5,24]. Factors such as mutation type (e.g., KIT vs. PDGFRA) also play a critical role in predicting response to therapy and overall survival. Patients with primary or secondary resistance to TKIs often have a poorer prognosis; this highlights the need for ongoing research into novel therapeutic strategies [10]. Overall, the prognosis of GIST patients requires a personalized approach, integrating surgical, medical, and supportive therapies to optimize outcomes [27].

Conclusion

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, presenting diagnostic and management challenges. These tumors, primarily found in the stomach and small intestine, can manifest as incidental findings or acute symptoms like bleeding, pain, and obstruction. Diagnosis involves imaging, endoscopy, and histopathological analysis, with CD117 and DOG-1 staining being crucial. Tyrosine kinase inhibitors (TKIs) like imatinib have revolutionized the treatment of advanced and metastatic GISTs, significantly improving outcomes, while surgical resection remains the cornerstone for localized GISTs. Despite these advances, perforation and metastatic disease are associated with poor prognosis and require a multidisciplinary approach for optimal management.

Patient consent

We confirm that we have obtained written, informed consent from the patient for the publication of this case report. The patient has been thoroughly informed about the details that will be published and understands the implications of the publication. The written consent is stored securely and is available for review by the editorial team upon request.