Case Of Tumor-induced Osteomalacia Research Articles

A Case of Tumor-Induced Osteomalacia (TIO) with Paradoxical Fibroblast Growth Factor 23 (FGF-23) Response After Surgical Excision

A Case of Tumor-Induced Osteomalacia (TIO) with Paradoxical Fibroblast Growth Factor 23 (FGF-23) Response After Surgical Excision

Abstract #1003989: A Rare Case of Tumor-Induced Osteomalacia Despite Resection of a Benign Glomangioma

Abstract #1003989: A Rare Case of Tumor-Induced Osteomalacia Despite Resection of a Benign Glomangioma

MON-500 A Case of Tumor-Induced Osteomalacia Caused by Metastatic Prostate Cancer

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia due to renal phosphate wasting. An overproduction of the phosphatonin fibroblast growth factor 23 (FGF-23) has been implicated in TIO pathogenesis. FGF-23 increases renal phosphate excretion by reducing the expression of sodium-dependent phosphate co-transporters NPT2a and NTP2c in the proximal tubules. TIO is most commonly associated with mesenchymal tumors. Epithelial tumors are estimated to account for only 5% of reported cases of TIO. Here we report a rare case of TIO associated with castration resistant metastatic prostate cancer. Clinical Case: A 59 year old male with high grade castration-resistant metastatic prostate adenocarcinoma presented with worsening fatigue and bone pain. Nine years before presentation, he was treated with prostatectomy, pelvic radiation, and taxotere followed by one year of luteinizing hormone-releasing hormone (LHRH) agonist. Bony metastases were identified 8 years later, and he was treated with a combination of LHRH agonist, RANK-ligand inhibitor denosumab, antiandrogenic therapy abiraterone and prednisone. Due to refractory disease, he received three cycles of sipuleucel-T, a cell-based cancer immunotherapy, and was enrolled in a phase 1B clinical trial involving enzalutamide. Laboratory evaluation included phosphorus 1.2 (2.5-4.5 mg/dL), urine phosphate excretion 1984 (400-1300 mg/24 hour), parathyroid hormone 110 (15-65pg/mL), calcium7.9 (8.7-10.2 mg/dL), vitamin D-25 85.3 (30-100mg/dL), inappropriately low vitamin D 1,25 40 (19.9-79.3 mg/dL) and FGF-23 387 (44-215 ref units/mL). Whole body scan showed widespread osteoblastic metastatic lesions. He was treated with high-dose calcitriol, vitamin D, calcium carbonate, and potassium phosphate with improvement in hypophosphatemia and bone pain. Clinical Lessons: Hypophosphatemic osteomalacia in the setting of advanced prostate cancer was first reported in 1975. The role of FGF-23 as a phosphatonin in such cases has since emerged, due to advancement of laboratory assays and improved understanding of the pathophysiology of TIO. Review of existing literature reveals five reported cases of prostate cancer-associated TIO with associated elevated FGF-23. This condition poses a diagnostic challenge, as TIO-related bone pain and weakness can be mistaken for that associated with bony metastases. Given the inability to resect widely metastatic disease, treatment of such cases consists of reducing tumor burden with chemotherapy and radiation and supplementation with calcitriol and phosphorus. While other FGF pathways have been implicated in prostate cancer-related angiogenesis, drug resistance, and metastases, the role FGF23 may play in an aggressive disease course warrants further investigation, particularly given it may represent a treatment target.

A case of tumor-induced osteomalacia caused by giant cell reparative granuloma in the maxilla

A case of tumor-induced osteomalacia caused by giant cell reparative granuloma in the maxilla

Is there any link between tumor-induced osteomalacia and psoriasis? A case report

BackgroundTumor-induced osteomalacia is an uncommon paraneoplastic syndrome caused by Fibroblast growth factor-23-secreting tumors. It is characterized by phosphaturia, hypophosphatemia, and a high plasma level of alkaline phosphatase.Case presentationWe report a young patient with psoriasis who had suffered from bone pain and muscle weakness for more than 6.5 years. He was finally diagnosed with tumor-induced osteomalacia. However, mistakenly attributing the patient’s signs and symptoms to psoriatic arthritis for a long time had resulted in multiple complications for the patient. Finally, the tumor was localized and surgically resected. This resulted in clinical improvements and the resolution of all biochemical abnormalities.ConclusionTo our knowledge, this is the second case of tumor-induced osteomalacia accompanied by psoriasis. There is growing evidence to suggest that Fibroblast growth factor-23 has a role in regulating immune function while an increased level of it may play a role in the pathogenesis of psoriasis. As a result, tumor-induced osteomalacia may affect the psoriasis clinical course by secreting a high amount of Fibroblast growth factor-23. On the other hand, several studies have showed an increased risk of malignancy among patients with psoriasis. Consequently, long-term psoriasis may predispose patients to Fibroblast growth factor-23-secreting tumors. Finally, as psoriasis is a common disease, this presentation may simply be a coincidence.

Abstract #513: Hypophosphatemia: A Case of Tumorinduced Osteomalacia

Abstract #513: Hypophosphatemia: A Case of Tumorinduced Osteomalacia

A case of tumor-induced osteomalacia in which recurrence and bilateral lung metastases occurred following tumor resection

A case of tumor-induced osteomalacia in which recurrence and bilateral lung metastases occurred following tumor resection

Surgical Treatments of Tumor-Induced Osteomalacia Lesions in Long Bones: Seventeen Cases with More Than One Year of Follow-up.

Tumor-induced osteomalacia is a rare and fascinating paraneoplastic syndrome usually caused by a small, benign phosphaturic mesenchymal tumor. Most tumors are treated surgically, but we are unaware of any reports that compare the results of curettage and segmental resection for lesions in long bones. Seventeen patients (ten male and seven female) with tumor-induced osteomalacia lesions in long bones, who underwent surgical treatment from December 2004 to August 2013 in our hospital, were included in this retrospective study. The mean follow-up (and standard deviation) was 35 ± 27 months (range, twelve to 116 months). The characteristics of the tumor and the effects of different surgical treatments (curettage compared with segmental resection) were evaluated. All patients showed typical clinical characteristics of tumor-induced osteomalacia, including elevated serum fibroblast growth factor-23 (FGF-23); 82% of tumors were in the epiphysis, and 82% grew eccentrically. The mean maximum diameter of the tumors was 2.4 ± 2.0 cm. The complete resection rates were similar for curettage (67%) and segmental resection (80%). However, the recurrence rate after curettage (50%) was higher than that after segmental resection (0%). The complete resection rate for secondary segmental resection (75%) was not different from that for primary segmental resection (83%). All of our cases of tumor-induced osteomalacia were caused by phosphaturic mesenchymal tumors. After successful removal of tumors, serum FGF-23 returned to normal within twenty-four hours and serum phosphorus levels returned to normal at a mean of 6.5 ± 3.5 days. Most lesions in long bones are located in the epiphysis, so curettage is first suggested to maintain joint function. If curettage is incomplete or there is a recurrence, secondary segmental resection should be considered curative. Changes of serum FGF-23 and phosphorus levels before and after the operation may be of prognostic help.

Concordance Between Whole-Body Scintigraphy 111In-Octreotide and 99mTc-Sestamibi Uptake in the Detection of Four Tumor-Induced Osteomalacia Cases

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumors secrete phosphaturic factors such as fibroblast growth factor-23, which increases renal phosphate excretion, causing hypophosphatemia and osteomalacia. These tumors have mesenchymal origin and are usually small and slow growing, and they can be located anywhere in the body. Because the cure for TIO includes its total resection, the challenge of the treatment is to locate it (1). Once TIOs express somatostatin receptor subtypes 2 and 5, In-octreotide (especially if combined with SPECT/CT [single photon emission computed tomography/computed tomography]) and more recently Ga-DOTANOC PET/CT (positron emission tomography/CT) and Ga-DOTATATE PET/CT have been shown to be excellent in their detection (2). Because TIOs are highly vascular, Tc-sestamibi scintigraphy (MIBI) has also been used for this purpose (3–5). We follow four patients (three women and one man; ages 12–46 y) whose clinical picture and laboratorial data suggested hypophosphatemic osteomalacia, which was confirmed by bone histomorphometry. They underwent whole-body scintigraphy In-Octreotide (Octreoscan) and Tcsestamibi to localize the tumor. Both methods revealed that the same body areas of focally increased tracer uptake in different anatomical sites in each patient (right leg, left foot, left leg, and left knee) were visualized in detail with magnetic resonance image (Figure 1). Histopathological findings after the tumor’s resection confirmed the existence of phosphaturic mesenchymal tumor, a mixed connective tissue variant. In these four patients, both methods (whole-body scintigraphy In-octreotide and MIBI) detected TIOs. For this reason, when Octreoscan is not available, we encourage TIO screening by MIBI.

Whole-body MR Imaging in Detecting Phosphaturic Mesenchymal Tumor (PMT) in Tumor-induced Hypophosphatemic Osteomalacia

We present 2 cases of tumor-induced osteomalacia (TIO). Both patients had histories of long-term bone and muscle pain. Laboratory data revealed hypophosphatemia. Whole-body magnetic resonance (MR) imaging (WB-MRI) clearly depicted a small subcutaneous mass in the left thigh of the first patient and a right acetabular mass in the second patient. These lesions were pathologically proven to be hemangiopericytoma-phosphaturic mesenchymal tumors (PMT).

A Case of Tumor-Induced Osteomalacia

A Case of Tumor-Induced Osteomalacia

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

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. (J Kor Endocrine Soc 22:142~148, 2007)