Tumor-induced osteomalacia due to a recurrent mesenchymal tumor overexpressing several growth factor receptors

[摘要] Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors.These tumors typically follow a benign clinical course and local recurrence occurs in !5% of cases. We investigated a49-year-old man with a recurrent mesenchymal phosphaturic tumor showing no signs of malignancy. The patient sufferedfrom chronic muscle weakness, myalgia and cramps. His medical record included the diagnosis of oncogenic osteomalacia,for which he was submitted to tumor resection in the left leg three times before. Laboratory examination showedhypophosphatemia, hyperphosphaturia and an elevated serum FGF23 level. A radical surgical approach (amputation) wasadvised, however, complete biochemical and clinical remission was not reached. Molecular analysis of the tumor cellsdemonstrated overexpression of growth factor receptors implicated in tumor angiogenesis and metastatic potential(platelet derived growth factor type A (PDGFRA), PDGFRB and vascular endothelial growth factor receptor) togetherwith increased expression of FGF23, x-linked-phosphate-regulating endopeptidase and KLOTHO. TIO is usually associatedwith benign phosphauturic tumors and, when identified, resection of the tumor leads to complete remission in the majorityof cases. The underlying pathophysiology of recurrences in these tumors is not known. This is the first report showingincreased expression of growth factor receptors in a locally aggressive but histopathologically benign phosphaturicmesenchymal tumor.

[学科分类] 血液学

[关键词] Adult;Male;White;Greece;Bone;Parathyroid;Tumours and neoplasia;Calcitriol;PTH;Osteomalacia;Paraneoplastic syndromes;Parathyroid adenoma;Tumour-induced osteomalacia;Myasthaenia;Myalgia;Cramps;Hypophosphataemia;Phosphate (urine);PTH;Alkaline phosphatase;Calcium (serum);Calcium (urine);Vitamin D;MRI;FGF23;Genetic analysis;Octreotide scan;Parathyroid scintigraphy;Amputation;Calcitriol;Calcimimetics;Cinacalcet;Phosphate supplements;Insight into disease pathogenesis or mechanism of therapy;July;2015