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

Aims Phosphaturic 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. FGF23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation of it 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 A total of 19 tumours from 14 cases previously diagnosed as PMT-MCT were retrieved, on which immunohistochemical staining, RT-PCR and FISH analysis were performed. Results 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 (9/12, 75%), FGFR1 (11/11, 100%), CD56 (12/14, 85.7%), and ERG (5/13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in 7 of 14 FFPE specimens and all 5 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. Conclusions It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without 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. This article is protected by copyright. All rights reserved.