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

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.

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Phosphaturic mesenchymal tumor of the occipitocervical region: Report of two rare cases and literature review

10.21203/rs.3.rs-68493/v1 ◽

2020 ◽

Author(s):

Linxiang Zhang ◽

Yiwei Hu ◽

Jijie Yan ◽

Jian Yang ◽

Guangjian Bai ◽

...

Keyword(s):

English Literature ◽

Postoperative Radiotherapy ◽

Bone Destruction ◽

Complete Resection ◽

Mesenchymal Tumor ◽

Phosphaturic Mesenchymal Tumor ◽

Tissue Mass ◽

Complex Anatomy ◽

Magnetic Resonance Imaging Mri ◽

The Right

Abstract BackgroundTumor-induced osteomalacia (TIO) is regarded as a rare paraneoplastic syndrome mainly caused by phosphaturic mesenchymal tumor (PMT). To our known, only 5 occipitocervical PMTs have been described in the world’s English literature. We reported two rare cases of occipitocervical PMT, and conducted a retrospective analysis of these 7 cases. The purpose of this study is to discuss the clinical characteristics and treatment of occipitocervical PMT.Case PresentationBoth patients were middle-aged females, and had a long-standing bone pain. In case 1, there were no abnormalities in biochemical indicators. The blood phosphorus was normal and alkaline phosphatase (ALP) was elevated in case 2. Magnetic resonance imaging (MRI) suggested that osteolytic bone destruction accompanied by a soft tissue mass in left C1-2 vertebra (case 1). In case 2, the bone destruction was located on the right C1-2 and the clivus. Then both patients underwent complete resection of tumor, and case 2 also received adjuvant radiotherapy, the histopathology revealed a PMT. Case 2 suffered recurrence during 5-year follow-up.ConclusionsOccipitocervical PMT is quite rare, and only 5 cases have been reported in the literature. Currently, complete resection of the tumor is the best option. The surgery is difficult, and requires delicate operation due to the complex anatomy of the occipitocervical region. Postoperative radiotherapy has little effect on local control. And further research is needed to confirm the effectiveness of the newly-emerged therapies.

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Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia

Medicina ◽

10.3390/medicina56010034 ◽

2020 ◽

Vol 56 (1) ◽

pp. 34

Author(s):

Cornelia Then ◽

Evelyn Asbach ◽

Harald Bartsch ◽

Niklas Thon ◽

Christian Betz ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Olfactory Neuroblastoma ◽

Mesenchymal Tumor ◽

Fibroblast Growth ◽

Phosphaturic Mesenchymal Tumor ◽

Oncogenic Osteomalacia ◽

Pet Ct ◽

Fgf 23

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

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Sternal Phosphaturic Mesenchymal Tumor-Induced Osteomalacia, Diagnosis and Management: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.456 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A224-A225

Author(s):

Mopelola Adetola Adeyemo ◽

Aili Guo

Keyword(s):

Ct Scan ◽

Functional Status ◽

Muscle Weakness ◽

Bone Pain ◽

Mesenchymal Tumor ◽

Phosphaturic Mesenchymal Tumor ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

History Of ◽

Fgf 23

Abstract Background: Tumor induced osteomalacia (TIO) is a rare paraneoplastic disorder in which overproduction of fibroblast growth factor-23 (FGF-23) by mesenchymal tumor results in decreased renal phosphorus reabsorption and low to inappropriately normal 1,25-dihydroxyvitamin D, leading to hypophosphatemia and osteomalacia. Patients often present with bone pain, fractures, muscle weakness, and progressive decline in mobility. Due to the nonspecific nature of presenting symptoms of TIO diagnosis is often delayed. Clinical Case: A 55-year-old male presented with complaints of chest pain, shortness of breath, and generalized weakness following a ground level fall. Patient also reported a 10-year history of osteoarthritis with chronic back pain and 1-year history of generalized weakness, resulting in significant decline in functional status. On work-up, the initial CT scan of chest revealed multiple fractures including ribs, manubrium, scapula, and pubic rami. Subsequent biochemical evaluation was remarkable for hypophosphatemia to low of 1.3 mg/dL (2.4 - 5.0 mg/dL), low of 1,25-dihydroxyvitamin D of 13.1 pg/ml (19.9 - 79.3 pg/mL), reduced tubular phosphate reabsorption rate of 28% (normal > 80%) ratifying for renal phosphate wasting, normal iPTH level, and elevated serum FGF-23 level of 460 (normal < 180). Then, localization imaging for TIO was performed. After PET/CT scan showing increased uptake at the sternal area suggestive of lytic metastasis, subsequent CT angiogram of the chest identified mottled, irregular, mildly expansile appearance of the sternal manubrium. Sternal biopsy revealed phosphaturic mesenchymal tumor with positive FGF 23 mRNA expression. Surgical resection was delayed due to poor functional status and concurrent discovery of an EBV-positive nasopharyngeal carcinoma. Prior to surgery patient was treated with phosphorus and calcitriol supplements. Post-operatively serum phosphorus and FGF-23 levels were normalized. Patient also improved clinically. Patients treatment course was complicated by secondary hyperparathyroidism; however, this improved following surgery. Conclusion: Diagnosis of TIO can be delayed due to its nonspecific symptoms. Thus, in patients with chronic bone pain, muscle weakness, and atraumatic fractures, TIO should be kept on the differential and these patients should undergo thorough biochemical and imaging evaluation. Tumor localization could be challenging. Patients should be managed with supplements of active vitamin D and phosphorus with goal to normalize phosphorus level to prevent further bone demineralization prior to surgery. However, surgical intervention remains the mainstay of management as this is curative of TIO.

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Malignant phosphaturic mesenchymal tumor-ossifying fibroma-like subtype: a case report and literature review

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04558-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hongyu Qin ◽

Hao Zeng ◽

Hao Li ◽

Shuangshuang Yuan ◽

Jinsong Yang

Keyword(s):

Malignant Transformation ◽

Serum Alkaline Phosphatase ◽

Histopathological Examination ◽

Tumor Resection ◽

Clinical Manifestations ◽

Iliac Bone ◽

Mesenchymal Tumor ◽

Ossifying Fibroma ◽

Phosphaturic Mesenchymal Tumor ◽

Postoperative Symptoms

Abstract Background A phosphaturic mesenchymal tumor (PMT) is classified into four histological subtypes: mixed connective tissue, osteoblast-like, non-ossifying fibroma-like, and ossifying fibroma-like. The ossifying fibroma-like subtype being extremely rare. Most PMTs are benign, with a minimal number becoming malignant after recurrence. In this study, we report a case of recurrence and malignant transformation of PMT-ossifying fibroma-like subtype in the left hip bone. Case presentation Here, we report the clinical manifestations, histology, pathological features, and treatment of a 57-year-old Chinese woman with a recurrent and malignant ossifying fibroma-like subtype PMT of the left iliac bone. The tumor was first discovered 3 years ago when the patient underwent surgery to remove the tumor. Precisely 2 years and 6 months after the operation, the pain in the left hip reappeared. After 6 months, the patient went to our hospital for treatment. After the tumor resection, the postoperative symptoms improved significantly, and the serum alkaline phosphatase level returned to normal. Based on clinical manifestations, evaluation of serum biochemical indicators, X-ray examination, computerized tomography scan of the pelvis, and histopathological examination of the two operations, the patient was finally diagnosed with a recurring and malignant transformation of the left iliac bone phosphaturic mesenchymal tumor-ossifying fibroma-like subtype. No tumor recurrence was found during the follow-up 15 months after the operation. Conclusions This case increases the awareness of a rare malignant subtype of PMT and provides a valuable reference for the diagnosis of this disease.

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Peptide Receptor Radionuclide Therapy for a Phosphaturic Mesenchymal Tumor

Case Reports in Oncology ◽

10.1159/000510334 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1373-1380

Author(s):

Simon Häfliger ◽

Ann-Katrin Seidel ◽

Eric Schoch ◽

Jan Reichmann ◽

Damian Wild ◽

...

Keyword(s):

Radionuclide Therapy ◽

Fibroblast Growth Factor 23 ◽

Somatostatin Receptors ◽

Peptide Receptor Radionuclide Therapy ◽

Mesenchymal Tumor ◽

Surgical Removal ◽

Phosphaturic Mesenchymal Tumor ◽

Peptide Receptor ◽

Wasting Syndrome ◽

Fgf 23

Tumor-induced osteomalacia is a very rare paraneoplastic syndrome. It can be caused by phosphaturic mesenchymal tumor (PMT), a generally benign tumor that produces fibroblast growth factor 23 (FGF-23), which can cause a severe renal phosphate wasting syndrome. Upon complete surgical removal of the tumor, FGF-23 normalizes and the osteomalacia is cured. In cases in which surgery is not feasible, radiofrequency ablation (RFA) is the treatment of choice. We describe a case with a PMT situated in the sacrum, in close proximity to the sacral plexus. Both surgery and RFA were considered potentially nerve damaging. Since the tumor showed expression of somatostatin receptors, we opted for a peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTATOC. However, the therapy did not show the expected success, since the FGF-23 level had even temporarily increased. The patient was then successfully treated with RFA. A partial remission of the tumor was achieved and FGF-23 levels nearly normalized. Despite some severe neurological side effects, the patient showed a remarkable clinical improvement, with no symptoms of osteomalacia within a few weeks.

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Phosphaturic mesenchymal tumor of spinal nerve in a patient with osteomalacia and multiple fractures

Acta Neuropathologica ◽

10.1007/s00401-010-0648-3 ◽

2010 ◽

Vol 119 (3) ◽

pp. 379-380 ◽

Cited By ~ 5

Author(s):

Wojciech Biernat ◽

Sonia Kaniuka ◽

Mirosław Stempniewicz ◽

Daniel Ręcławowicz ◽

Krzysztof Sworczak

Keyword(s):

Spinal Nerve ◽

Mesenchymal Tumor ◽

Phosphaturic Mesenchymal Tumor ◽

Multiple Fractures

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A Giant Sacrococcygeal Chordoma: Case Report and Literature Review

Advances in Bioscience and Clinical Medicine ◽

10.7575/aiac.abcmed.v.7n.2p.60 ◽

2019 ◽

Vol 7 (2) ◽

pp. 60

Author(s):

Xiang Yang ◽

Seidu A. Richard ◽

Wei Zhao ◽

Jiagang Liu ◽

Siqing Huang

Keyword(s):

Tumor Resection ◽

Immunohistochemical Analysis ◽

Low Grade ◽

Case Presentation ◽

Primary Bone Tumors ◽

Case Surgery ◽

Primary Bone ◽

Malignant Lesions ◽

Magnetic Resonance Imaging Mri ◽

Tomographic Angiography

Introduction: Chordomas are rare low-grade malignant lesions that are mostly seen in the spine. They constitute about 1% of intracranial tumors and 3-4% of all primary bone tumors. The principal spinal location is usually the sacrococcygeal and infrequently the sphenooccipital and cervical areas. Case Presentation: We present a 74-year-old man with a huge sacrococcygeal mass extending to both buttocks. Computerized tomography (CT-scan) and magnetic resonance imaging (MRI) as well as computerized tomographic angiography (CTA) evaluations were suggestive to chordoma. Immunohistochemical analysis confirmed the diagnosis after the patient was successfully operated on. All aggravating symptoms resolved after the operation. Conclusion: The management of giant sacrococcygeal chordomas can be very challenging but with all-inclusive treatment, complete cure is achievable although recurrence can occur. In our case, surgery alone was curative. Preoperative CTA aided us in achieving total tumor resection.

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MON-352 When Osteoporosis Does Not Make Sense: Tumor-Induced Osteomalacia

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1174 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Pawarid Techathaveewat ◽

Ghada Elshimy ◽

Kelvin Tran ◽

Karyne L Vinales ◽

Ricardo R Correa

Keyword(s):

The Body ◽

Mesenchymal Tumor ◽

Renal Tubules ◽

Mineral Density ◽

Multiple Fractures ◽

Post Surgery ◽

Surgery Patient ◽

Multiple Imaging ◽

History Of ◽

Fgf 23

Abstract Background: Tumor-induced Osteomalacia (TIO) is a rare paraneoplastic disorder that relates to excess FGF-23 secretion from mesenchymal tumors. Typical presentations include weakness, severe bone pain, but more importantly; multiple false or true fractures. Severe Hypophosphatemia with hyperphosphaturia is one of the pathognomonic findings due to FGF-23 action on renal tubules as phosphaturic agent. Multiple imaging modalities usually required as tumor can be in any size and anywhere in the body. Case: 58 yo male with past medical history of multiple fractures: bilateral rib cage, and metatarsal, dextroscoliosis who present to endocrine clinic due to low bone mineral density (BMD). On initial visit, screening bloodwork done was unremarkable except for mild elevation of Alkaline Phosphatase and extremely low phosphorus (1.2). 24 Urine phosphorus ordered which was elevated but it was thought to be nutrition related thus phosphorus replacement was prescribed (4 times per day). On follow up, repeat labs noted again with severe hypophosphatemia with elevated FePhos. DEXA was also performed which noted with T score -4.0 of lumbar spine. During that appointment, he informed also that currently in the process of evaluating right lung mass with biopsy resulted with benign mesenchymal tumor which he was happy to hear. TIO was then suspicious to be the cause of decrease BMD along with history of multiple fractures and height loss. Subsequently, FGF-23 staining was then made to the biopsy sample which was positive thus confirming the diagnosis. Patient then underwent surgical resection of the tumor which post-surgery, patient experienced overall symptoms improvement, resolution of phosphatemia, as well as significant improvement of BMD without additional therapy besides calcium and vitamin D. Discussion: Osteomalacia is a pathological bone disease involving poor mineralization of existing bone during remodeling phrase. It is commonly involved with chronic hypophosphatemia and/or hypocalcemia. Persistent decrease in calcium-phosphate product leads to reduction in bone mineralization activity and bone stiffness with Bowing deformities of the long bone being one of the common findings as well as false fracture.In TIO, FGF-23 is excessively secreted by mesenchymal tumor that is usually difficult to locate due to its small size. When FGF-Receptor is activated, NaPi-2a transcription is reduced in proximal tubule cells which leads to Phosphate excretion and wasting.TIO is a curable disease once tumor is located and surgically removed thus it is important for providers to be aware of it and pursue diagnostic work up when high suspicious. One of the most common reason for misdiagnosis is due to standard metabolic panel on its own does not include phosphorus level which is crucial. TIO has to be distinguish from osteoporosis as Bisphosphonates is not indicated as treatment which is first line for the latter.

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Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the thoracic spine

Journal of Neurosurgery Spine ◽

10.3171/2009.1.spine08351 ◽

2009 ◽

Vol 10 (4) ◽

pp. 329-333 ◽

Cited By ~ 19

Author(s):

Elena Pirola ◽

Francesco Vergani ◽

Paolo Casiraghi ◽

Eugenio Biagio Leone ◽

Paolo Guerra ◽

...

Keyword(s):

Thoracic Spine ◽

Paraneoplastic Syndrome ◽

Tumor Resection ◽

Mesenchymal Tumor ◽

Phosphaturic Mesenchymal Tumor ◽

Oncogenic Osteomalacia ◽

Mesenchymal Tumors ◽

History Of ◽

Complete Tumor

Phosphaturic mesenchymal tumors that cause the paraneoplastic syndrome known as oncogenic osteomalacia are rare. The authors report on the case of a 57-year-old man with a history of osteomalacia and in whom was diagnosed a thoracic spine tumor at the T-4 level. Complete tumor resection was accomplished. The histological diagnosis was phosphaturic mesenchymal tumor (mixed connective tissue variant). After lesion removal, the paraneoplastic syndrome resolved. At the 24-month follow-up, no recurrence of the disease was observed. The clinical presentation, surgical technique, and follow-up in this case were reviewed in detail.

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