title: From epistaxis to bone pain-report of two cases illustrating the clinicopathological spectrum of phosphaturic mesenchymal tumour with fibroblast growth factor receptor 1 immunohistochemical and cytogenetic analyses.
abstract: OBJECTIVE
  Phosphaturic mesenchymal tumour (PMT) is a rare, recently described neoplastic entity. It is characterized by distinct histological features, which often occur together with oncogenic osteomalacia. Recently, a novel FN1-FGFR1 gene fusion has been described in a subset of PMTs. The aim of this study is to characterise the clinicopathological features of two PMTs, with FGFR1 immunohistochemical and cytogenetic analyses.
  
  
  RESULTS
  We present two contrasting cases of PMT, one occurring in the sinonasal region, and the other occurring in bone (proximal femur). In the former, local effects, including epistaxis and anosmia, dominated the clinical presentation, whereas the latter case presented with refractory bone pain, muscle weakness, and occult osteomalacia, the cause of which was only identified after 2 years. Both tumours showed characteristic histological features of PMT, including a monomorphic proliferation of round to ovoid cells, osteoclast-like multinucleated giant cells, and areas of 'smudgy' basophilic calcifications. Chromogenic in-situ hybridization showed fibroblast growth factor FGF-23 expression by the sinonasal tumour. By using immunohistochemistry, we also demonstrated, for the first time, FGF receptor 1 (FGFR1) protein overexpression in this tumour, for which FN1-FGFR1 gene fusion was not detected by fluorescence in-situ hybridization.
  
  
  CONCLUSIONS
  Our findings indicate that up-regulation of FGFR1 in phosphaturic mesenchymal tumours can occur via mechanisms other than FN1-FGFR1 fusion, raising the possibility of FGFR1 overexpression being a potential common pathway with pathophysiological and therapeutic implications.
authors.affiliation: Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Mok
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Jeffrey Huey Yew
authors.initials: JH
authors.lastname: Lum
authors.affiliation: Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Petersson
mesh_terms: D001859:Bone Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*; D020732:Cytogenetic Analysis; D004844:Epistaxis / Q000209:etiology; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000473:pathology*; D009669:Nose Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*; D010146:Pain / Q000209:etiology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis*; D012983:Soft Tissue Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*
chemical_list: C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: hypophosphataemia; oncogenic osteomalacia; paraneoplasia; phosphaturia; phosphaturic mesenchymal tumour; tumour-induced rickets