Tumor-induced osteomalacia combined with increased bone resorption postoperatively: A case report.

RATIONALE: Rare tumor-induced osteomalacia (TIO) usually resulted in bone pain, fragility fractures and muscle weakness in clinical, which is caused by the reduced phosphate reabsorption, thus impaired mineralization of the bone matrix and free energy transfer. The specific problems in postsurgical patients are obscure although surgical removal of the tumor is the only definitive treatment. Here, we documented a female TIO patient who suffered more severe bone pain and muscle spasms post-operation. Further, we presented and discussed our explanation for the unexpected symptoms. PATIENT CONCERNS: The main symptoms were whole-body pain and muscle weakness. The patient also presented with osteoporosis and multiple fractures. DIAGNOSIS: Elevated serum fibroblast growth factor 23 (FGF23) level and hypophosphatemia indicated the diagnosis of TIO. Positron emission tomography (PET)/computed tomography (CT) with 68 Ga-DOTATATE located the tumor in the dorsolateral part of the left foot. Histopathological examinations confirmed the diagnosis. INTERVENTIONS: The tumor was surgically removed immediately after the diagnosis of TIO and localization of the tumor. Postoperatively, calcium carbonate supplement treatment was continued. OUTCOMES: Two days after surgery, the serum FGF23 level was decreased to the normal range. Five days after surgery, N-terminal propeptide of type I procollagen and ß-CrossLaps (ß-CTx) had a remarkable increase. A month after surgery, the patient N-terminal propeptide of type I procollagen and ß-CTx levels were decreased obviously, and serum FGF23, phosphate and 24h urinary phosphate were in the normal range. LESSONS: We report a female patient who presented with osteoporosis and fractures. She was found with an elevation of FGF23 and diagnosis with TIO after PET/CT scanning. After surgically removing the tumor, the patient experienced more severe bone pain and muscle spasms. Active bone remodeling might be the reason for the symptoms. Further study will reveal the specific mechanism for this abnormal bone metabolism.

[FGF23 tumor induced osteomalacia].

Tumor induced osteomalacia is a rare acquired disease. The cause is a mesenchymal tumor secreting fibroblast growth factor 23 (FGF23). An excessive amount of FGF 23 disrupts the metabolism of phosphorus and vitamin D, which leads to severe paraneoplastic syndrome, manifested in the form of multiple fractures, severe pain in the bones and generalized myopathy. With oncogenic osteomalacia, a complete cure is possible with radical resection of the tumor. Unfortunately, localization, small size of formations and rare frequency of occurrence lead to the fact that the disease remains unrecognized for a long time and leads to severe, disabling consequences. A step-by-step approach to diagnosis improves treatment outcomes. First, a thorough anamnesis is collected, then functional visualization is performed and the diagnosis is confirmed by anatomical visualization of the tumor. After that, the method of choice is a surgical treatment. If resection is not possible, then conservative therapy with active metabolites of vitamin D and phosphorus salts is indicated. New therapeutic approaches, such as the antibody to FGF23 or the pan-inhibitor of receptors to FGF, are actively developing. This article provides an overview of modern approaches to the diagnosis and treatment of this disease.

Comparison of surgical treatments of tumor-induced osteomalacia in different locations in the lower limbs: A retrospective study.

Tumor-induced osteomalacia (TIO) is a rare disease that behaves benignly. Very few reports about the features of the responsible tumors according to anatomical locations have been presented.In this retrospective study of 53 patients with TIO-associated tumors in the foot/ankle, tibia and femur, we compared preoperative, postoperative, and follow-up courses, including alkaline phosphatase, phosphorus, and fibroblast growth factor 23, to compare the characteristics of TIO-associated tumors in these 3 locations (level of evidence: therapeutic level III).Patients in the foot/ankle group had longer disease courses and therefore a significantly higher complication rate (P < .001). All TIO-associated tumors in the foot/ankle group involved soft tissue (P = .021), whereas most lesions in the tibia group involved bone, and therefore had much higher concentrations of alkaline phosphatase (P = .020). Additionally, serum phosphorus took much longer to normalize after surgery in the foot/ankle group than that in the other 2 groups (P = .004). Consequently, symptom remission was much better in the tibia and femur groups (P = .008). Moreover, the Ki 67 index in TIO-associated tumors was significantly higher in the foot/ankle group (P < .001) and the recurrence rate in this group was markedly higher (P = .002).The TIO-associated tumors in the foot/ankle are characteristically of occult onset, more soft-tissue involvement, and more readily recurrence. More knowledge and examinations are necessary to enable early diagnosis, radical treatments, and minimize recurrence. New therapies are welcomed and needed.

Sinonasal hemangiopericytoma caused hypophosphatemic osteomalacia: A case report.

RATIONALE: Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic syndrome featured with fibroblast growth factor 23 (FGF23) secretion primarily by benign mesenchymal tumors and sometimes by malignancies. TIO diagnosis and treatment is often delayed because TIO usually has nonspecific generalized bone pain and weakness, and location of TIO tumor is quite challenging. Very few TIO caused by sinonasal hemangiopericytoma have been reported in the literature. PATIENT CONCERNS: A 40-year-old Chinese woman presented with diffuse bone pain for more than 1 year. Laboratory examination showed hypophosphatemia, hyperphosphaturia, hypocalcemia, an elevated serum alkaline phosphatase (ALP) level and bone-specific ALP level. Imaging studies revealed low bone mineral density (BMD) and multiple pseudofractures at the ribs. F-18 fluorodeoxyglucose positron emission tomography was negative in searching for tumors. Because no tumor was located, the patient was treated with oral phosphate, calcium, and alfacalcidol, and achieved great relief in her symptoms and improvement in BMD. Six years later, the patient had breast cancer surgery and received chemotherapy, and still had hypophosphatemia. During this time, nasopharyngo-fiberscope showed nasal mass in her left nasal cavity. Then she had her nasal polyps removed and surprisingly the serum phosphate became normal. DIAGNOSES AND INTERVENTIONS: The patient had the nasal mass resected, and pathological diagnosis of the nasal mass was sinonasal hemangiopericytoma. Immunohistochemical analysis was positive for FGF23. Thus the final diagnosis was osteomalacia induced by sinonasal hemangiopericytoma. Phosphate supplementation and alfacalcidol were discontinued. OUTCOMES: The patient had normal serum phosphate after 6-month follow-up. LESSONS: By presenting this case, we hope to remind clinicians that in patients with osteomalacia with undetermined reason and intranasal polypoid mass, sinonasal hemangiopericytoma should be suspected.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Tumor-Induced Osteomalacia: an Up-to-Date Review.

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. TIO is usually induced by small, slowly growing tumors of mesenchymal origin (phosphaturic mesenchymal tumor mixed connective tissue variant [PMTMCT]). Nonspecific symptoms including fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and often lead to a delay in treatment. The prognosis of TIO is excellent following complete resection of the neoplasm, which leads to the rapid and complete reversal of all symptoms. If the tumor cannot be detected, treatment relies on supplementation with phosphate and active vitamin D compounds. Subsequent radiotherapy in case of incompletely resected tumors or definitive radiotherapy in unresectable tumors is an important treatment option to avoid recurrence or metastasis even though this occurs rarely. Due to the risk of recurrence or late metastases, long-term monitoring is required even in TIO patients diagnosed with a benign tumor.

Tumor-induced osteomalacia: an important cause of adult-onset hypophosphatemic osteomalacia in China: Report of 39 cases and review of the literature.

Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia. Tumor resection leads to cure. We investigated the clinical characteristics of TIO, diagnostic methods, and course after tumor resection in Beijing, China, and compared them with 269 previous published reports of TIO. A total of 94 patients with adult-onset hypophosphatemic osteomalacia were seen over a 6-year period (January, 2004 to May, 2010) in Peking Union Medical College Hospital. After physical examination (PE), all patients underwent technetium-99m octreotide scintigraphy ((99) Tc(m) -OCT). Tumors were removed after localization. The results demonstrated that 46 of 94 hypophosphatemic osteomalacia patients had high uptake in (99) Tc(m) -OCT imaging. Forty of them underwent tumor resection with the TIO diagnosis established in 37 patients. In 2 patients, the tumor was discovered on PE but not by (99) Tc(m) -OCT. The gender distribution was equal (M/F = 19/20). Average age was 42 ± 14 years. In 35 patients (90%), the serum phosphorus concentration returned to normal in 5.5 ± 3.0 days after tumor resection. Most of the tumors (85%) were classified as phosphaturic mesenchymal tumor (PMT) or mixed connective tissue variant (PMTMCT). Recurrence of disease was suggested in 3 patients (9%). When combined with the 269 cases reported in the literature, the mean age and sex distribution were similar. The tumors were of bone (40%) and soft tissue (55%) origins, with 42% of the tumors being found in the lower extremities. In summary, TIO is an important cause of adult-onset hypophosphatemia in China. (99) Tc(m) -OCT imaging successfully localized the tumor in the overwhelming majority of patients. Successful removal of tumors leads to cure in most cases, but recurrence should be sought by long-term follow-up.

Incidental prostatic stromal tumor of uncertain malignant potential (STUMP): histopathological and immunohistochemical findings.

Stromal prostate tumors are rare neoplastic proliferative lesions that have been classified into prostatic stromal tumor of uncertain malignant potential (STUMP) and prostatic stromal sarcoma (SS) based on these criteria: stromal cellularity, presence of mitotic figures, necrosis, and stromal overgrowth. A prostatic stromal tumor of uncertain malignant potential (STUMP) is a non-epithelial, mesenchymal spindle-cell tumor that can be classified as a specialized stromal tumor of the prostate. STUMPs have the capability to diffusely infiltrate the prostate gland and extend into adjacent tissues. Furthermore, they often recur and this is why they are considered as neoplastic entities. STUMPs usually tend to be not aggressive, but occasional cases have been reported with an extension into adjacent tissues. A few cases develop a sarcomatous dedifferentiation. A 67-year-old male referred to the Department of Urology, Sapienza Rome University, with acute urinary retention (AUR) and bladder overdistention. Digital rectal examination (DRE) showed the presence of a severe prostatic hyperplasia and a transvesical prostatic adenomectomy (TVPA) was performed. The pathological evaluation performed at the Department of Pathology, Sapienza Rome University, revealed an incidental diagnosis of prostatic STUMP. The patient's follow-up is made every year with transrectal ultrasonography and nuclear magnetic resonance with spectroscopy, and every two years with a transperineal prostate biopsy to exclude a progression to a stromal sarcoma. After 5 years of follow-up the STUMP is still detectable but there is no sign of sarcoma. As a result of its relative rarity and lack of long-term follow-up, the prognosis of STUMP is unclear. Therapy varies from a wait-and-see approach to a radical retropubic prostatectomy.