Oncogenic hypophosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1

<jats:p>Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D<jats:sub>3</jats:sub> (1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffa's fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub> were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.</jats:p>