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Kim, Jung, Kim, Kim, Kim, Shin, Kim, and Kim: A Case of Tumor-induced Osteomalacia with Elevated Fibroblast Growth Factor-23
Case Report
Journal of Korean Endocrine Society

Journal of Korean Endocrine Society 2007; 22(2): 142-148.

Published online: 20 April 2007

DOI: https://doi.org/10.3803/jkes.2007.22.2.142

A Case of Tumor-induced Osteomalacia with Elevated Fibroblast Growth Factor-23

Hae Sung Kim1, Hyun Seung Jung1, Hee Jung Kim1, Sung Yeon Kim1, Sang Wan Kim1, 3, Chan Soo Shin1, 3, Chong Jai Kim2, Seong Yeon Kim1, 3

1Department of Internal Medicine, Seoul National University College of Medicine, Korea.

2Department of Pathology, Seoul National University College of Medicine, Korea.

3The Hormone Research Center, Seoul National University Hospital Clinical Research Institute, Korea.

Received 30 October 2006       Accepted 9 March 2007

Copyright © 2007 Korean Endocrine Society

Abstract

Tumor-induced osteomalacia (TIO), a paraneoplastic disease, is characterized by hypophosphatemia, and caused by renal phosphate wasting inappropriately, normal or decreased 1, 25(OH)2D3 production, and defective calcification of cartilage and bone. Because the removal of the responsible tumor normalizes phosphate metabolism, unidentified humoral phosphaturic factors (phosphatonin) are believed to be responsible for this syndrome. These factors include fibroblast growth factor (FGF)-23, secreted frizzled-related protein-4 and matrix extracellular phosphoglycoprotein. However, no case of TIO producing FGF-23 has been clearly reported in Korea. Herein, a case of TIO producing FGF-23 in a 45-year-old woman is reported. The patient presented with a large tumor on her buttock, with severe bone and muscle pain. A histological examination of the tumor revealed a mixed connective tissue tumor, consisting of deposition of calcified materials and surrounding primitive spindle cells, with prominent vascularity. Whether FGF-23 is a secreted factor, as well as its levels of expression in tumors were investigated. An immunohistochemical study showed the tumor cells to be FGF-23 positive. Furthermore, the levels of serum FGF-23 were extremely high and an RT-PCR analysis, using total RNA from the tumor, revealed the abundant expression of FGF-23 mRNA. After removal of the tumor, all the biochemical and hormonal abnormalities disappeared, with marked symptomatic improvement.

Keywords: Fibroblast growth factor-23, Tumor-induced osteomalacia

Figures and Tables

Fig. 1
Plain x-ray film of both lower legs at initial admission (1990). Radiography showing radiolucent line and loss of cortical continuity (pseudofracture) of the upper diaphysis of the left fibula.
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Fig. 2
Pelvic CT in patient who was presented with a large buttock mass shows large dumbbell shape soft tissue mass posterior to rectum and left side buttock.
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Fig. 3
H & E and immunohistochemical staining for FGF-23 in tumor. A, Tumor cells are composed of small bland spindle to ovoid cells that produce a distinctive eosinophillic smudge matrix with deposition of calcified materials (grungy pattern). H&E, × 400; B, The prominent branching vascular patterns mimic those seen in hemangiopericytoma/solitary fibrous tumor. H&E, × 400; C, Positive staining of FR tumor with antiFGF-23 antibody under high power. Staining was cytoplasmic and granular. Arrows indicate the presence of immunostained cells (brown staining), × 400.
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Fig. 4
RT-PCR analysis of FGF-23 mRNA in tumor. Agarose gels with separated PCR products are shown. Lanes: 1, molecular weight markers; 2, adrenal adenoma tissue from a patient with primary aldosteronism; 3, tumor tissue. The predicted sizes of the PCR products in base pairs are indicated to the right of the panel.
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Fig. 5
Serum FGF-23 levels in patients with TIO. Mean serum FGF-23 levels in patients with TIO or chronic renal failure were significantly higher than in normal controls. # case patient, * P < 0.05.
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