Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant

AimsPhosphaturic mesenchymal tumour, mixed connective tissue variant (PMT‐MCT), is a tumour of uncertain differentiation, characterised by ‘smudgy/grungy’ calcification and vitamin D‐resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT‐MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour‐associated osteomalacia or histologically definitive PMT‐MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings.Methods and resultsA total of 19 tumours from 14 cases diagnosed previously as PMT‐MCT were retrieved, on which immunohistochemical staining, reverse transcription–polymerase chain reaction (RT–PCR) and fluorescence in‐situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft‐tissue PMT‐MCT, while PMT‐MCT of bone and multiple PMT‐MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin‐fixed paraffin‐embedded (FFPE) specimens and all five frozen specimens by RT–PCR. The level of FGF23 mRNA, which was determined by real‐time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement.ConclusionsIt was considered that PMT‐MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)–FGFR1 fusion gene. The authors propose that the histology of PMT‐MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis.