Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA-mutant GISTs

Riccardo Ricci, Maria Cristina Giustiniani, Marco Gessi, Paola Lanza, Federica Castri, Alberto Biondi, Roberto Persiani, Fabio M. Vecchio, Mauro Risio

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Cellular and Molecular Medicine
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • gastrointestinal stromal tumour
  • inflammatory fibroid polyp
  • interstitial cell of Cajal
  • PDGFRA-mutant syndrome
  • syndromic gastrointestinal stromal tumour
  • syndromic inflammatory fibroid polyp
  • telocyte
  • telocyte hyperplasia
  • telocytoma
  • tumour precursor

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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