Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek´s tumors)

Abstract

Vanek's tumor (inflammatory fibroid polyp) is a rare benign lesion occurring throughout the digestive tract. Histologically, two patterns can be recognized. Classical Vanek's tumor contains concentric formations of proliferating spindle cells which are CD34 positive. Atypical, inflammatory pseudotumor-like Vanek's tumor lacks concentric formations and is CD34 negative. Recently, mutations in platelet-derived growth factor receptor alpha (PDGFRA) were reported in gastric and small intestinal Vanek's tumors. In this study, KIT exons 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and a part of exon 15 BRAF for point mutation V600E were screened in 23 cases of Vanek's tumor, both classical (n = 16) and inflammatory pseudotumor-like (n = 7). No mutations in all analyzed exons of KIT and BRAF and in exon 14 of PDGFRA were detected. Six Vanek's tumors harbored activating mutations in PDGFRA exons 12 (n = 5) and 18 (n = 1) respectively: S566_E571delinsK (n = 1), S566_E571delinsR (n = 4), and D842 del (n = 1). The mutations were detected in the classical (n = 5), as well as inflammatory pseudotumor-like (n = 1) Vanek's tumors. The results of this study suggest that the two morphological patterns of Vanek's tumor more probably represent only variants of one type of tumor than two different lesions. Furthermore, BRAF mutations were not shown to drive growth of PDGFRA wild-type Vanek's tumors.

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

“…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.…”

PDGFRA-mutant syndrome

“…In fact, like fibrous tumors, inflammatory fibroid polyps may feature a prominent hyalinization, lack of a polypoid shape and, especially in intestinal cases, involvement of visceral layers deeper than submucosa, absence of eosinophils and lack of an onion-skin pattern, and CD34 staining. [31][32][33][34][35] In particular, fibrous tumors resemble the sclerotic stage of inflammatory fibroid polyps described by Kim and Kim. 33 These findings, together with the common PDGFRA-mutant status, in our opinion, well support the inclusion of fibrous tumors in the inflammatory fibroid polyp family.…”

Inflammatory Fibroid Polyp of the Gallbladder Bearing a Platelet-Derived Growth Factor Receptor Alpha Mutation

“…11 Accordingly, the reported gallbladder tumor would belong to the ''gastric'' type of IFPs; however, considering the specific PDGFRA mutation instead of the exon harboring it, it is noteworthy that the only IFP with a PDGFRA del D842 reported before the one described in this study was actually found in the small bowel, namely in the duodenum. 12 Thus, in a perspective of possible site-specific PDGFRA mutations of IFPs, it seems conceivable that the present gallbladder case is more akin to a comparatively unusual intestinal-type of IFP bearing the PDGFRA exon 18 mutation del D842 than to the ''gastric'' IFP family sharing a PDGFRA exon 18 mutation in a broad sense.…”

“…12 The low rate of mutated versus wild-type DNA likely depends on the large normal cell component present in IFP, 1 which ''dilutes'' the genotypically altered fibroblast-like cells. 6 With regard to the differential diagnosis of the investigated mass, the finding of a PDGFRA mutation by itself excludes all but one mesenchymal lesion, which can exceptionally occur in the gallbladder: gastrointestinal stromal tumor (GIST).…”