Inflammatory fibroid polyp ( Vanek ’ s polyp ) : a case report and literature review

Inflammatory fibroid polyp (IFP) is a benign uncommon lesion (1%-4% of gastric benign lesions), originated from the submucosa of the gastrointestinal tract. Its origin is controversial and immunohistochemical studies of lesions have largely refuted the possible vascular, neural or smooth muscle origin. Recent studies suggest a neoplastic etiology due to a mutation, in some cases, in the alpha-type platelet-derived growth factor receptor gene (PDGFRa). Our objective is to report the case of a patient aged 70 years, with gastric IFP, comparing her immunohistochemical profile with those of other studies, and a brief review of the literature.


intRoDuCtion
The inflammatory fibroid polyp (IFP) is a benign lesion that arises from the submucosa of the gastrointestinal (GI) tract (1)(2)(3) , most commonly in the antrum (70%) and ileum (20%) and, only occasionally, in the duodenum and jejunum (4)(5)(6)(7) .Its frequency ranges from 1% to 4% of diagnoses among benign stomach lesions, and usually occurs between the fifth and the seventh decade of life (1,2) .Malignancy is a rare event (2) , however, up to 8% of IFPs have been described as concomitant lesions with adenoma or carcinoma (8) .
Several studies on structural and immunohistochemical analysis of lesion has been conducted in order to clarify the origin of the IFPs, which, however, remains controversial (4,(15)(16)(17) .Several immunohistochemical studies have refuted a potential to vascular or neural origin for the lesion, since IFPs resulted negative for factor VIII-Ra and S-100, respectively (18,19) , or a smooth muscle origin due to a negative reaction for alpha smooth muscle actin (SMA), desmin and myoglobin (18) .Some studies have promoted the idea that fibroblasts are the main cells, primitive mesenchymal cells (18)(19)(20)(21) or even dendritic cells (22) .Other, more recent, have shown a mutation in the alpha type receptor for the platelet derived growth factor (PDGFRa), suggesting a possible neoplastic factor in the etiology of this lesion (8,14,16) .
We report the case of a female patient aged 70 years with gastric IFP comparing her morphological and immunohistochemical features with the actual studies, and we reviewed the literature on this lesion.

CaSE REPoRt
Case A 70-year-old female patient with diabetes mellitus, undergoing well differentiated endometrioid endometrial adenocarcinoma follow-up, presented nausea, vomiting, and bloody stools lasting one week.Upper digestive endoscopy demonstrated expanded diaphragmatic hiatus and hiatal hernia with 3 cm slip, and pedunculated polyp in the antrum region, covered by preserved mucosa, similar to the adjacent, measuring 10.5935/1676-2444.20150021 3 cm in diameter.There were no other abnormalities, and the endoscopic polypectomy of the lesion was analyzed.

Histopathological analysis
Histopathological examination revealed a well-defined polypoid lesion, composed of proliferation of spindle cell elements, a prominent network of small capillaries and inflammatory cells located in the submucosa.The cells have ovoid nuclei, uniform chromatin, and abundant cytoplasm.The stroma is myxoid edematous, concentrically arranged around blood vessels with "onion skin" pattern.The inflammatory cells are predominantly composed of eosinophils (Figure 1).The overlying mucosa was preserved.Special staining for H. pylori caused negative result.
The differential diagnosis is challenging, even at the microscopic level, and immunohistochemical analysis is performed to differentiate from other tumors, such as gastrointestinal stromal tumor (GIST), inflammatory myofibroblastic tumor (IMT) and schwannoma (14,16) .IMT is very similar to IFP, with myofibroblast proliferation and mixed inflammatory component (9) .The Inflammatory fibroid polyp (Vanek's polyp): a case report and literature review
IFP may have variable reactivity for smooth muscle actin, CD34, CD117 (c-kit), and S-100 protein (5,7,10,12,22) .In this case, the immunohistochemical analysis excluded GIST (negative for CD117), inflammatory myofibroblastic tumor (negative for smooth muscle actin) and schwannoma (negative for S-100).Its etiology is still controversial (5, 10-12, 15-17, 22) , but several hypotheses have been proposed, the most accepted, until recently, the inflammatory theory (2) , according to which, IFP originates due to excessive tissue reaction to damage applied on the gastrointestinal mucosa, as chemical, mechanical or biological factors (2,5,6,(10)(11)(12)15) . It isbelieved that these factors act on mucosal fibroblasts and myofibroblasts, stimulating its growth (2) .An allergic etiology has also been proposed due to the presence of eosinophilic infiltration (9,6,11,17) , however, in most cases there is no medical history of allergies and eosinophilia, which is present in only 4% of patients (16,17) .The emergence of these polyps in gastric location has been associated to Helicobacter pylori infection, entailing the hypothesis of an immune response during a chronic infection by this bacterium (1,2,8,17,26) .Some studies suggest that gastric IFPs are more frequent in patients with atrophic gastritis and pernicious anemia (8) .Other autoimmune diseases have also been linked to IFP, such as sarcoidosis, rheumatoid arthritis and ankylosing spondylitis, which confirms the possibility of an immune reaction as a contributing factor (1,11,17) .
In this report, the spindle cells of the lesion were positive for CD34 and vimentin, and negative for SMA actin, factor VIII-Ra, CD117 (c-kit) and S-100 protein.However, the positivity for factor VIII-Ra and smooth muscle actin in the vessels walls showed the rich vascularity of the lesion, which may indicate a secondary involvement of vascular proliferation (18) .Our results corroborate the literature when indicating that the lesion presents a possible neural, vascular or smooth muscle origin (18,19) , encouraging the idea that the main cells are fibroblasts or primitive mesenchymal cells, primarily because it is strongly positive for vimentin and CD34 (18)(19)(20)(21) .In a study of 14 IFP cases, three cases were negative for CD-34, and all of positive cases for this marker had concentric stromal proliferation (18) .The authors concluded that IFP with concentric proliferation may have a different histogenesis from IFP without this type of stromal pattern, and that it may originate from a subpopulation of dendritic interstitial cells (18,22) .Our case presented stroma concentrically organized around the vessels and positive for marker CD34.
Recent studies have shown mutations in exons 12 (26,27) or 18 (26,28) and, less frequently, in exon 14 (26) of PDGFRa gene (chromosome 4q12), suggesting a possible neoplastic factor in the etiology of this lesion (26)(27)(28) .A total of 145 IFP cases, 55.2% had mutations in exons 12 or 18 of PDGFRa gene, and only two cases presented mutation in exon 14 (26) .Studies on mutation of this lesion have shown that a type of unidentified mesenchymal stem cells of the GI tract submucosa is mutated, developing a tumor (26,27) .Thus, IFPs present a possible major component of spindle cells, recognized as fibroblast and primitive mesenchymal cells, and studies on Mutation Research should be conducted to elucidate the mechanisms that lead to the origin of this lesion.