PDGFRA-mutant syndrome

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

“…We herein report a detailed morphological and immunophenotypical analysis of the diffuse stromal proliferation described in the GI wall in PDGFRA ‐mutant syndrome7 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…”

“…However, a third type of GI lesion, consisting of an intramural diffuse stromal proliferation variably referred to as “submucosal fibrous thickening,” “intestinal fibrosis,” “increased submucosal connective tissue,” “thickened submucosa” or “expanded submucosa”, has often been described in this genetic setting, both in humans and in mice 8, 9, 10. It consists of a CD34+ stromal proliferation, that variously involves the entire thickness of the GI tract, often heavily affecting the submucosa (Figure 1A‐C).…”

“…With regard to IFPs, we have already described examples stemming from the “submucosal thickening” found in an individual affected by PDGFRA ‐mutant syndrome 9. Herein, we show also that there appears to be a gradual cytologic progression from TCs constituting the aforementioned thickening to stromal cells forming IFP, with a gradual loss of both slender cytoplasmic processes and relative cell elongation, accompanied by the acquisition of a relatively plumper morphology in the presence of a persisting, although overall less intense, positivity for PDGFRA (Figure 2C‐G).…”

“…However, to date, no ICCH has been detected either in human germline PDGFRA ‐mutants or in mice generated for the conditional expression of mutant PDGFRA , arguing against a relationship between ICCs and PDGFRA ‐driven GISTs. Conversely, GI stromal cell hyperplasia has been described in these conditions, especially at submucosal level 7, 8, 9, 10…”

“…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.…”