Abstract
PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT‐mutant settings but not in PDGFRA‐mutant ones, challenging the precursor role of ICC for PDGFRA‐driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall “fibrosis” has been reported in germline PDGFRA‐mutants. Taking the opportunity offered by its presence in a germline PDGFRA‐mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA‐mutant counterpart of germline KIT mutation‐associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA‐mutant GISTs. We propose the term “telocytoma” for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic (“telocytary”) essence of this tumour, unlike IFP, which rather evokes an inflammatory‐hyperplastic lesion.
Highlights
Inflammatory fibroid polyps (IFPs) are benign, polypoid lesions usually centred in the submucosa of the gastrointestinal (GI) tract, with a predilection for gastric antrum
The gastric tissues investigated were from the only member of a previously published germline platelet-derived growth factor receptor alpha (PDGFRA)-mutant kindred who featured a remarkably marked stromal proliferation of the gastroduodenal wall together with IFPs and GI stromal tumour (GIST).[9]
We report a detailed morphological and immunophenotypical analysis of the diffuse stromal proliferation described in the GI wall in PDGFRA-mutant syndrome[7] and of its relationship with IFP and GIST, by exploiting the exceptional opportunity offered by its remarkable manifestation, together with the presence of these tumours, in an individual from a kindred previously published by the authors.[9]
Summary
Inflammatory fibroid polyps (IFPs) are benign, polypoid lesions usually centred in the submucosa of the gastrointestinal (GI) tract, with a predilection for gastric antrum. They consist of a proliferation of spindle, stellate or epithelioid mesenchymal cells harboured in a vascularized stroma, infiltrated by inflammatory cells (often with numerous eosinophils). We previously published a kindred bearing a germline mutation (CC?TT at 1957-58) that led to a Leu for Pro substitution at 653 (P653L) in PDGFRA gene.[9] The proband featured GI tumours encompassing GISTs, IFPs (including tumours previously described as “fibrous tumours”26) and a lipoma, and an intramural diffuse stromal cell proliferation, heavily affecting the submucosa, in the stomach and proximal duodenum. We carried out a morphological and immunophenotypical investigation of the histotype of these stromal cells in order to establish their possible morphogenetic and/or pathogenetic relationship with synchronous IFPs and GISTs
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