||Digestive organs: Inflammatory fibroid polyps
|Other names||Vanek's tumor|
|| Inflammatory fibroid polyps (IFP) are benign mesenchymal tumors which originate from the submucosa of the stomach or the small bowel. IFP occur rarely in the colon and in the esophagus.
In 1949 the Czech pathologist Josef Vanek reported on six cases of gastric lesion which he referred to as gastric submucosal granuloma with eosinophilic infiltration: "A peculiar lesion was observed consisting of more or less loose collagenous tissue with fibroblasts, lymphocytes, and eosinophilic polymorphonuclear leukocytes. The pathologic tissue thus composed appeared as a circumscribed focus in the submucosa, spreading toward the mucosa of the stomach. Macroscopically, it caused a bulging of the mucosa, and in some cases even a polypous formation." (Vanek, 1949).
At the same time the German pathologist Franz Bolck noticed these lesions, too, and referred to them as granuloblastoma of the stomach (for review see: Bolck and Katenkamp, 1982). The term inflammatory fibroid polyp was introduced four years after the initial description (Helwig and Ranier, 1953). Since then several hundred reports, mainly case series and reports on single cases, have been published which predominantly focussed on clinical and morphologic aspects. Notably, inflammatory fibroid polyps have been regarded as reactive lesions for decades. In 2008, however, the neoplastic nature of IFP became evident by the detection of activating PDGFRA mutations in these tumors (Schildhaus et al., 2008).
|Phenotype / cell stem origin|| A progenitor cell of inflammatory fibroid polyps has not yet been established. However, Lasota et al. have discussed whether specialized PDGF dependent mesenchymal progenitor cells in the so-called villus clusters might represent progenitors (Lasota et al., 2009).|
|Etiology|| Historically, IFP have been thought to represent a reactive inflammatory lesion. It was assumed that IFP might be associated for example with helicobacter infection or type A gastritis. After discovery of the activating PDGFRA mutations in these tumors it became apparent that IFP represent true neoplasms which are - so far as we know today - obviously driven by activating mutations in the PDGFRA gene.|
|Epidemiology|| Inflammatory fibroid polyps are rare lesions which affect predominantly adults. Notably, the mean age of patients with gastric tumors is significantly higher compared with IFP of the small bowel (72 years vs. 53 years) (Huss et al., 2012). IFP account for 0.1 - 3.0 % of all gastric polyps (Carmack et al., 2009).|
|Clinics|| Inflammatory fibroid polyps arise from the submucosa and tend to form polypoid lesions. They occur predominantly in the stomach (mainly in the antrum region). Most IFP remain undiagnosed for a long time or are incidental findings at endoscopy. Larger polyps tend to erode and ulcerate superficially with local bleeding representing the most common clinical symptom. Very rarely large tumors of several centimeters size have led to obstruction of the pylorus or the upper gastric sphincter. Most inflammatory fibroid polyps, however, are small measuring only few millimeters.|
IFP of the small bowel may also give rise to local bleeding. Major complications in this location, however, are intussusceptions and invaginations. At least in adolescents and adults, IFP are a frequent cause of this severe and acute disease.
Inflammatory fibroid polyps are benign and do not recur nor metastasize.
|Pathology|| Inflammatory fibroid polyps are mostly small lesions of only few millimeters size. We have, however, seen some tumors of up to 10 centimeters (Huss et al., 2012). IFP characteristically arise from the submucosa and grow through the lamina propria towards the surface of the mucosa where typically an ulceration is found. IFP consist of bland spindled cells which are characteristically arranged in whorls or in an onion skin like fashion around blood vessels or mucosal glands. The matrix consists of fine fibrillar collagen but might also be collagen-rich. |
The "classic" (or gastric) type which was originally described by Josef Vanek is characterized by a heavy inflammatory infiltrate which is rich in eosinophilic granulocytes. These lesions show a plenty of spindle cells but only little collagen.
We and others have shown that there is another morphological subtype ("intestinal type") which, in contrast, is paucicellular and collagen-rich. Both cellular elements, fibroblastic spindle cells and inflammatory infiltrate, are less numerous. These tumors tend to be larger than those of the gastric type (Huss et al., 2012).
Outside of ulcerations no necroses are found. There is no considerable proliferative activity as mitoses of the spindle cell are almost never seen and Ki67 is below 1%.
Immunohistochemically, the spindle cells are mostly positive for CD34 but this feature may be absent especially in the intestinal type. PDGFRA expression is frequently found. Immunostains for KIT, DOG-1 as well as S100 and EMA are consistently negative. This may be important in the differential diagnosis of gastrointestinal stromal tumors, perineuriomas and other spindle cell lesions of the gastrointestinal tract.
| Inflammatory fibroid polyp of the stomach. Histological appearance of the "classic" (gastric) type with heavy inflammatory infiltrate.|
|Treatment|| Most inflammatory fibroid polyps can be endoscopically removed. Only rarely surgery is necessary.|
|Prognosis|| Benign tumor, no risk for an aggressive clinical behavior. Patient may, however, suffer from severe disturbances due to mucosal bleeding, local obstruction or intussusception.|
| Granuloblastomas of the stomach (so-called eosinophilic granulomas)-- a variant of fibrous histiocytomas?|
| Bolck F, Katenkamp D.|
| Pathol Res Pract. 1981 May;171(3-4):336-44.|
| Management of gastric polyps: a pathology-based guide for gastroenterologists.|
| Carmack SW, Genta RM, Graham DY, Lauwers GY.|
| Nat Rev Gastroenterol Hepatol. 2009 Jun;6(6):331-41. doi: 10.1038/nrgastro.2009.70. (REVIEW)|
| Inflammatory fibroid polyps of the stomach.|
| Helwig EB, Ranier A.|
| Surg Gynecol Obstet. 1953 Mar;96(3):335-67.|
| Activating PDGFRA mutations in inflammatory fibroid polyps occur in exons 12, 14 and 18 and are associated with tumour localization.|
| Huss S, Wardelmann E, Goltz D, Binot E, Hartmann W, Merkelbach-Bruse S, Buttner R, Schildhaus HU.|
| Histopathology. 2012 Jul;61(1):59-68. doi: 10.1111/j.1365-2559.2012.04203.x. Epub 2012 Mar 6.|
| Gain-of-function PDGFRA mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases.|
| Lasota J, Wang ZF, Sobin LH, Miettinen M.|
| Mod Pathol. 2009 Aug;22(8):1049-56. doi: 10.1038/modpathol.2009.62. Epub 2009 May 15.|
| Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene.|
| Schildhaus HU, Cavlar T, Binot E, Buttner R, Wardelmann E, Merkelbach-Bruse S.|
| J Pathol. 2008 Oct;216(2):176-82. doi: 10.1002/path.2393.|
| Gastric submucosal granuloma with eosinophilic infiltration.|
| Vanek J.|
| Am J Pathol. 1949 May;25(3):397-411.|