Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin.

Anke H Hautmann,Matthias G Hautmann,Martin Fleck,Elisabeth Huber,Patrick Hoffstetter,Josef Schroeder,Peter Wild,Christiane Girlich

doi:10.1155/2014/729387

Abstract

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.

Highlights

Tumor-induced osteomalacia (TIO) is a rare, acquired paraneoplastic disorder characterized by a renal phosphate leak leading to hypophosphatemia and deranged bone turnover
Additional radiographic investigations were not performed. This case report presents a patient with a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) leading to the rare disease tumor-induced osteomalacia (TIO)
The histopathology of tumors leading to TIO reveals in 70–80% of cases PMTMCTs [2] which are rare neoplasms occurring in approximately 53% of cases within bones, in 45% in soft tissue and in 3% of patients in the skin

Summary

Introduction

Tumor-induced osteomalacia (TIO) is a rare, acquired paraneoplastic disorder characterized by a renal phosphate leak leading to hypophosphatemia and deranged bone turnover. In TIO most tumors overexpress the protein fibroblast growth factor-23 (FGF-23) inhibiting renal phosphate reabsorption in the proximal tubules and acting as a phosphaturic factor [1, 3, 11]. In these cases, FGFR-23 levels are increased. Gallium Dotatate PET has emerged as a virtually ideal investigation to localize tumors causing TIO as well and performed better than F-FDG PET/CT in some studies and seems to be a promising diagnostic tool in patients in whom 111In-octreotide SPECT/CT prior failed to detect a tumor [15, 16]. If the responsible neoplasm is surgically removed, the abnormalities in phosphate wasting and in vitamin D metabolism typically dissolve in a few days

Materials and Methods

Case Report

Findings

Discussion