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Inflammatory fibroid polyp of the gastric antrum presenting as hypovolemic shock: Case report and literature review

Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the gastrointestinal tract, and represent less than 0.1% of all gastric polyps (1). These lesions most commonly affect older adults, especially those localizing to the gastric antrum. In children, IFPs more commonly occur in the small intestines and present as intussusception (2). IFPs arise from the submucosa and penetrate through the lamina propria leading to bulging of the mucosal layer. Rarely, they can ulcerate through the mucosa causing hemorrhage, leading to progressive blood loss and symptoms related to hypovolemic shock. Herein, we discuss a case of an adult woman who initially presented with a recent history of orthostatic hypotension and melena who was found to have an IFP of the gastric antrum evaluated by endoscopic visualization, biopsy and immunohistochemical analysis. A discussion involving the pathological characterization and management of IFP, followed by a brief review of the literature, is included in this article.


Introduction
Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the gastrointestinal tract, and represent less than 0.1% of all gastric polyps (1). These lesions most commonly affect older adults, especially those localizing to the gastric antrum. In children, IFPs more commonly occur in the small intestines and present as intussusception (2). IFPs arise from the submucosa and penetrate through the lamina propria leading to bulging of the mucosal layer. Rarely, they can ulcerate through the mucosa causing hemorrhage, leading to progressive blood loss and symptoms related to hypovolemic shock. Herein, we discuss a case of an adult woman who initially presented with a recent history of orthostatic hypotension and melena who was found to have an IFP of the gastric antrum evaluated by endoscopic visualization, biopsy and immunohistochemical analysis. A discussion involving the pathological characterization and management of IFP, followed by a brief review of the literature, is included in this article.

Case Report
A 65-year-old Puerto Rican woman with a past medical history of hypertension and asthma first presented to the emergency department with a one-day history of lightheadedness and a recent fall at home. The patient endorsed feeling generally unwell for several days, associated with two weeks of diarrhea, and was recovering with bed rest at home. On the day of presentation, while attempting to stand up from bed,

Summary
Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the submucosa of the gastrointestinal tract, and represent less than 0.1% of all gastric polyps. They are most commonly localized to the gastric antrum, small intestines and recto-sigmoid colon. IFPs are most commonly found incidentally upon endoscopic evaluation in the absence of symptoms. Presenting symptoms depend on the location of the tumor, although polyps located in the stomach most commonly present with epigastric pain and early satiety. Classic histologic features include perivascular onion skinning of spindle cells with an abundance of eosinophilic infiltration. The prompt diagnosis and management of IFP is essential due to its underlying risk for intussusception, outlet obstruction and acute hemorrhage. In addition, recent evidence has shown that IFP is driven by an activating mutation in the platelet derived growth factor receptor alpha (PDGFRA) gene, suggesting a neoplastic etiology. Herein, we discuss a case of a 65-year-old woman with an inflammatory fibroid polyp of the gastric antrum who initially presented with early hypovolemic shock and melena. Diagnosis was made by endoscopic visualization, biopsy and immunohistochemical analysis. The patient was initially found to be hypotensive and tachycardic. While taking a urine sample, the patient noticed black, tarry stools. She denied any abdominal pain, nausea, vomiting, dysphagia, early satiety or use of iron supplementation. The patient denied having an upper endoscopy or colonoscopy in the past and was not currently taking anticoagulation or antiplatelet therapy. Family history was significant for a maternal grandmother and niece with stomach cancer. Physical examination revealed dry mucous membranes, reduced skin turgor and guaiac positive stool. Initial laboratory studies revealed a hemoglobin of 8.3 mg/dL and mean corpuscular volume of 91.6 fL with normal electrolytes and kidney function.

Keywords
The patient was admitted to the hospital and given aggressive intravenous (IV) fluid resuscitation. A chest radiograph and computed tomography (CT) scan of the head were both negative for acute changes. CT abdomen/ pelvis revealed an antral mass, measuring 1.82 × 2.08 cm in greatest diameter, protruding within the gastric lumen with associated sub-centimeter perigastric lymph nodes ( Figure 1). No other sources of acute hemorrhage were identified. Upper endoscopy revealed a 3 cm ulcerated, semi-sessile mass in the gastric antrum with evidence of recent hemorrhage ( Figure 2). An endoscopic ultrasound of the antral mass showed it to be derived from the submucosa and extending through the mucosa, with no evidence of invasion to surrounding organs. A repeat upper endoscopy was completed for tumor resection using a snare technique.
Pathological evaluation showed a nodular proliferation of bland spindle cells, small vessels, and an eosinophil-rich inflammatory infiltrate localized primarily to the submucosa with extension into the mucosa of the gastric antrum ( Figure 3A-D). Immunohistochemistry analysis revealed positive staining for CD34 and negative staining for CD117, supporting the diagnosis of an inflammatory fibroid polyp. The patient tolerated the procedure and recovered without complications. Upon two-week followup evaluation, the patient's symptoms had resolved completely. An outpatient colonoscopy revealed no abnormalities.

Discussion
The inflammatory fibroid polyp, also known as a Vanek tumor/polyp, was first reported in 1949 by Vanek (3). The term inflammatory fibroid polyp was first proposed in 1953 by Helwig and Ranier (4). As a result, IFP has now been defined as a benign lesion of the GI tract derived from the submucosa. It is characterized pathologically by the presence of CD34 staining spindle cells, a prominent network of blood vessels, fibromyxoid stroma and an inflammatory infiltrate, typically dominated by eosinophils. Perivascular spindle cell "onion skinning" is present in about half of the lesions (5,6).
IFP must be differentiated from other benign and malignant spindle cell lesions including gastrointestinal stromal tumor (GIST), leiomyoma, leiomyosarcoma, schwannoma, and inflammatory myofibroblastic tumors (6,7). Definite diagnosis is made by immunohistochemical analysis. IFPs are most commonly positive for vimentin and CD34, and negative for S100, CD117 and desmin (5,7,8). The most common site of IFP was first reported at the gastric antrum (70%) followed by the small intestines (20%) in 1986 (9). However, the largest series of IFP to date (83 specimens) found the most commonly involved site to be the large intestines (37%), followed by the gastric antrum (23%) and small intestines (20%) (5).
The true pathogenesis of IFP is currently unknown. Historically, the etiology was thought to be the result of  polyp type (13).
Once the diagnosis of IFP is made, the decision to resect the polyp should be based on both the clinical presentation of the patient and the expertise of the gastroenterologist. Patients presenting with early satiety, chronic epigastric pain, or obstruction should undergo resection. Those who present with an acutely bleeding polyp should be treated swiftly by localizing the lesion and achieving adequate hemostasis. Once the patient is stabilized, eventual polyp resection is suggested to avoid similar adverse events in the future. Following IFP resection, pathological analysis should be initiated to confirm the diagnosis and rule out any potential for malignancy. Finally, because IFPs have no documented malignant potential, routine endoscopic follow-up is not recommended for both post-operative and asymptomatic patients (13).  (Table 1), with ages ranging from 19-93 year-old, averaging 64.3, including 19 women (51.4%) and 18 men (48.6%) (8,. The gastric antrum was the most commonly involved site, n = 22 (59.5%), followed by the pyloric and pre-pyloric area, n = 5 (13.5%), gastric cardia, n = 2 (5.4%), gastric body, an inflammatory response to an underlying granuloma. The development of a submucosal granuloma is often associated with an irritating stimulus (e.g. trauma, tuberculosis, helicobacter pylori, Crohn disease, sarcoidosis) (10). However, IFP has been showed to occur more frequently in patients with a family history of gastrointestinal polyps (11). More recently, in the first genetic study involving IFP, activating mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene were present in 70% of cases (12). This evidence suggests instead that IFP may represent a true neoplastic lesion driven by activating mutations in PDGFRA. However, no evidence of invasive growth or aggressive metastatic spread has been reported to our knowledge.
The therapeutic strategy of IFP can be viewed similar to that of other benign gastrointestinal polyps. More than 90% of gastrointestinal polyps discovered by routine endoscopic evaluation are present in asymptomatic patients and have no malignant potential (13). However, these polyps cannot be distinguished from those that require further intervention by gross examination alone. Therefore, histological analysis is always indicated in determining the polyp type and presence of underlying dysplasia (14). Additional diagnostic modalities including immunohistochemistry staining, tandem biopsies, and endoscopic ultrasound (EUS) may also be necessary to correctly identify the   9%). The most common presenting symptom was epigastric pain, n = 7 (18.9%) followed by anemia, n = 6 (16.2%). The most common treatment modality was endoscopic polypectomy, n = 10 (47.6%), followed by surgical gastrectomy, n = 9 (42.9%), and endoscopic submucosal dissection (ESD) (4.8%). One case regressed after helicobacter pylori eradication. Complications were rarely reported, with three cases (8.1%) developing gastric adenocarcinoma in close proximity to the IFP and two cases resulting in gastric outlet obstruction (5.4%). Only one polyp (2.7%) was described as having recurred after treatment.

Conclusion
The case herein represents a rare entity leading to the common presentation of an acute upper gastrointestinal hemorrhage. IFP remains one of the rarest benign tumors of the gastrointestinal tract, and appears most commonly in the gastric antrum and the rectosigmoid colon. Its pathogenesis is not completely understood. However, it is now widely viewed as a PDGFRAdriven benign neoplasm. Patients rarely present with symptoms, but may endorse epigastric pain, early satiety or symptoms related to obstruction. Diagnosis is made primarily with endoscopic biopsy, however additional studies including immunohistochemistry analysis may be required. Therapeutic management is based on the patient's clinical presentation and the expertise of the procedural team. Resection is generally recommended for symptomatic patients and for bleeding IFP lesions. Routine endoscopic evaluation is not indicated due to the lack of evidence for malignant transformation and recurrence.