Pattern of growth of a gastric inflammatory fibroid polyp with PDGFRA overexpression

A 73-year-old man with esophageal varices due to hepatitis C virus-induced cirrhosis has been followed by endoscopy since 1994. When a smooth, flat elevation first appeared in the gastric antrum in 2004 ([Fig. 1 a]), our provisional diagnosis was gastric verrucosa.

Fig. 1 Pattern of growth of the gastric polyp. Endoscopic appearance in a 2004, b 2007, c March 2008, and d September 2008, which shows the findings representative for inflammatory fibroid polyp.

Follow-up endoscopy over the next 2 years showed no remarkable change, but in 2007 the lesion grew bigger ([Fig. 1 b]) and a small ulcer appeared on the apex in March 2008 ([Fig. 1 c]). Mesenchymal tumors such as gastrointestinal stromal tumor or malignant lymphoma were suspected but biopsy was inconclusive. After another 6 months the ulcer had extended downward ([Fig. 1 d]) and exhibited the characteristic gross appearance of an inflammatory fibroid polyp (IFP). The polyp, removed endoscopically, was composed of spindle cells arranged in an onionskin-like concentric formation in the submucosal layer, accompanied by inflammatory cell infiltration, which predominantly consisted of eosinophils ([Fig. 2]).

Fig. 2 Polypectomy specimen shows the onionskin-like concentric formation of the spindle cells and dense inflammatory cell infiltration, predominantly eosinophils (hematoxylin and eosin, × 100).

On immunohistochemistry, the spindle cells were diffusely positive for PDGFRA (platelet-derived growth factor receptor α) ([Fig. 3]), focally positive for CD34, and negative for KIT.

Fig. 3 Immunostaining exhibiting spindle cells diffusely positive for PDGFRA (× 100).

These findings were consistent with those of the classical IFP with concentric formation [1].

IFP is a rare mesenchymal tumor of the gastrointestinal tract and its natural history is unknown [2]. Our report demonstrates that it might take several years for gastric IFP to grow from an endoscopically discernible elevation into the characteristic submucosal tumor. Follow-up endoscopy enabled not only the establishment of the correct diagnosis before resection but also endoscopic treatment before surgical intervention became inevitable. Since the first description by Vanek [3] in 1949, IFP has been regarded as a reactive polyp rather than a neoplastic lesion. In 2008, however, a seminal study by Schildhaus et al. first demonstrated ubiquitous PDGFRA overexpression and frequent gain-of-functional PDGFRA mutation in IFPs [1]. These findings, supported by subsequent studies [4] [5], point to the neoplastic nature of IFP and the current case supports a crucial role for PDGFRA activation in gastric IFP.

Endoscopy_UCTN_Code_CCL_1AB_2AD_3AB

References

• 1 Schildhaus H U, Cavlar T, Binot E et al. Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene.  J Pathol. 2008;  216 176-182
• 2 Bhatti I, Melhado R, Leeder P et al. Clinical challenges and images in GI. Image 3: Inflammatory fibroid polyp.  Gastroenterol. 2008;  135 1465, 1808
• 3 Vanek J. Gastric submucosal granuloma with eosinophilic infiltration.  Am J Pathol. 1949;  25 397-411
• 4 Daum O, Hatlove J, Mandys V et al. Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek’s tumors).  Virchows Arch. 2010;  456 491-497
• 5 Lasota J, Wang Z F, Sobin L H et al. Gain-of-function PDGFRA mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases.  Mod Pathol. 2009;  22 1049-1056