Gain-of-Function PDGFRA Mutations, Previously Reported in Gastrointestinal Stromal Tumors, Are Common in Small Intestinal Inflammatory Fibroid Polyps. A Study on 60 Cases
J Lasota, Z-F Wang, LH Sobin, M Miettinen. AFIP, Washington, DC
Background: Inflammatory fibroid polyp (IFP) is a rare benign lesion occurring throughout the digestive tract. Usually it is solitary tumor, characterized by a proliferation of highly vascular fibrous tissue infiltrated by inflammatory cells. IFP etiology and histogenesis is not known. Recently, mutations in platelet-derived growth factor receptor alfa (PDGFRA) and PDGFRA expression have been reported in gastric IFPs. Similar PDGFRA mutations were reported in a subset of GISTs.
Design: Sixty well characterized small intestinal IFPs were retrieved from the AFIP files. Expression of PDGFRA, KIT, CD34, smooth muscle actin (SMA), desmin and S100 was evaluated immunohistochemically. DNA samples obtained from FFPE tumors were screened for mutations in PDGFRA exons 12, 14 and 18 by PCR amplification and direct sequencing of PCR products.
Results: The patient age varied from 13 to 83 years (median 53.5). The male to female ratio was 1:1. Of 32 IFPs 27 were found in the ileum and only 5 in the jejunum. The follow-up data were available in 16 cases; 7 patients were alive (135 to 345 months) with no evidence of the disease, while 9 died of unrelated or unknown causes after 36 to 205 months. Histologically the polyps consisted of an admixture of dendritic-shaped or epithelioid-polygonal mesenchymal cells and inflammatory cells, especially eosinophilic granulocytes. There was a variable collagenous or myxoid extracellular matrix. Strong PDGFRA expression was seen in 97 % of IFPs. CD34 was expressed in 11 tumors. Two IFPs showed SMA expression and one tumor was S100 positive. All IFPs were KIT and desmin negative. PDGFRA mutations were identified in 52% of IFPs. There were 25 deletions, 3 deletion-insertions, duplication and single nucleotide substitution in exon 12 and deletion in exon 18.
Conclusions: PDGFRA expression and mutational activation is common in the small intestinal IFPs as it is in their gastric counterparts. However, in small intestinal tumors, 97% of mutations were found in exon 12 and only one in exon 18. In contrast, gastric IFPs were previously reported to have predominantly exon 18 mutations. Similar PDGFRA mutations were reported in GISTs and are considered a driving force in their pathogenesis. Thus, IFPs should be considered PDGFRA driven benign neoplasms.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 23, Monday Afternoon