UNASSIGNED: Phosphaturic mesenchymal tumors (PMTs) are rare bone neoplasms with diverse clinical presentations, often posing diagnostic challenges.
UNASSIGNED: We describe the case of a 37-year-old female schoolteacher with a PMT localized in the distal femur. Diagnostic indicators included hypophosphatemia, hyperphosphaturia, elevated fibroblast growth factor-23 levels, and clinical symptoms of osteomalacia. Surgical management involved tumor resection and limb salvage surgery with a megaprosthesis. The post-operative period was uneventful, leading to a stable discharge. On follow-up, the patient showed no signs of recurrence, regained full ambulation, remained pain-free, and resumed teaching comfortably.
UNASSIGNED: This case highlights the importance of considering PMT in patients with unusual clinical symptoms, accompanied by hypophosphatemia, hyperphosphaturia, and osteomalacia, and demonstrates successful surgical management, leading to a favorable outcome.

Phosphaturic mesenchymal tumor (PMT) is a rare tumor causing bone complications and myopathy. Histologically, PMT displays a mix of spindled cells, osteoclast-like giant cells, basophilic matrix, and flocculent or \"grungy\" calcification. Here we describe a case of PMT in the right hip and proximal femur, initially suspected to be multiple myeloma, presenting with osteolytic lesions and elevated alkaline phosphatase. Tests for malignancy were negative, but a subsequent biopsy confirmed PMT. The patient underwent hip biopsy, femur resection, and hemiarthroplasty, with follow-up MRI recommended.

The present case report is aimed to highlight the difficulty and the reason for the delayed diagnosis of phosphaturic mesenchymal tumors, emphasizing the need of standardized protocols for diagnosis, surgery and follow-up in high-volume hospitals. The clinical signs and symptoms, diagnostic and therapeutic procedures, immunohistological features were analyzed. Delayed diagnosis of phosphaturic mesenchymal tumor was primarily due to non-specific clinical symptoms such as fatigue, muscular and bone pain, and multiple fractures. This cryptic clinical picture made the diagnosis tricky that led to treatment of patient for non-specific pain and stress fractures before to consider the tumor-induced osteomalacia syndrome. Some well-documented studies were found in the literature in which the history of trauma is a critical trigger of glomus tumors. Extra-subungual tumors most frequently occur in the knee and ankle regions, particularly among young adults, and the diagnosis is typically made approximately 7.2 years after initial symptom onset. The difficult tumor localization represented an additional obstacle to the prompt treatment, leading to delayed curative surgery.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors-PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy.

Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109/L), neutropenia (1.28 × 109/L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO.

OBJECTIVE: We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with tumor-induced osteomalacia (TIO), with a focus on patients with non-localizing and malignant TIO.
METHODS: This is a retrospective cohort of TIO patients in an academic medical center, diagnosed between January 1998 to May 2023. We described their demographics, biochemistries, tumor features, localization, treatment and complications.
RESULTS: Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. 20 (40%) had persistent disease due to wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus or baseline fibroblast growth factor-23 (FGF23) levels between localizing versus non-localizing groups, and malignant versus non-malignant groups. Lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. 60% of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R=0.566, p<0.001) but was not associated with malignancy risk (p=0.479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (p=0.025), and recurrence after initial cure (p=0.013) were factors significantly associated with malignancy. The non-localizing group had lower survival than localizing group (p=0.0097).
CONCLUSIONS: TIO is a condition with significant morbidity. Very high FGF23 level and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in non-localizing TIO should be further explored.

Phosphaturic mesenchymal tumors (PMTs) are rare tumors that can cause tumor-induced osteomalacia (TIO) through overproduction of FGF23, a peptide hormone that causes renal phosphate wasting and reduced osteoblastic activity. The diagnosis of PMTs can be difficult to make as the presenting symptoms are non-specific. Although PMT is a rare entity, most cases are benign in nature, not requiring further intervention after surgery, as resection is typically curative. Here, we present a unique case of malignant PMT with de novo liver metastasis in a female patient who presented with TIO and underwent surgical resection of her primary lesion with subsequent regression of her liver metastasis. Moreover, we analyze a review of literature and discuss the importance of a timely diagnosis of this rare phenomenon. It is encouraged that providers strongly consider a diagnosis of PMT in patients with otherwise unexplained bone pain, fatigue, weakness, especially if accompanied with hypophosphatemia. Further studies are also warranted to identify prognostic factors that predict a PMT\'s malignant potential as they may help identify possible therapeutic targets.
Phosphaturic mesenchymal tumor with spread to the liver: A case report and literature review Phosphaturic mesenchymal tumors (PMTs) are rare tumors that can cause bone loss through the excess production of a signal named FGF23. This hormone causes the kidneys to lose phosphate and reduces the body’s ability to build new bone. PMTs are incredibly rare and difficult to diagnose especially since the presenting symptoms can be seen in several different diseases. Although PMT is rare, most cases are benign, only requiring surgery. We are presenting a unique case of a patient who presented with PMT in her right thigh and had evidence that the disease spread to her liver. Our patient underwent surgical resection of her thigh lesion and subsequently had improvement of her liver lesion. In our study, we analyze a review of literature and discuss the importance of a timely diagnosis of this rare phenomenon. It is encouraged that providers strongly consider a diagnosis of PMT in patients with otherwise unexplained bone pain, fatigue, weakness, especially if accompanied by low phosphate levels. Further studies are also warranted to identify prognostic factors that predict a PMT’s malignant potential as they may help identify possible therapeutic targets.

UNASSIGNED: An uncommon medical disorder known as tumor-induced osteomalacia (TIO) is characterized by severe hypophosphatemia, renal phosphate wasting, and osteomalacia due to a tumor. TIO has recently been linked to a particular kind of tumor known as phosphaturic mesenchymal tumor (PMT). PMTs release phosphatonins, such as fibroblast growth factor-23 (FGF23), which elevates serum levels of FGF23, leading to phosphate wasting and osteomalacia. However, due to their infrequent occurrence and vague symptoms, such as bone pain, myopathies, arthralgias, fractures, and weakness, the diagnosis of PMTs is often delayed or misdiagnosed. In this case report, a rare case of PMT in the proximal femur resulted in TIO, and it highlights the long and difficult journey from symptom onset to correct diagnosis and successful surgical management.
UNASSIGNED: A 51-year-old woman endured persistent joint pain, muscle weakness, and fatigue for 2 years. Despite having no known health issues, she suffered from hip pain that spreads to her knees and ankles, and tingling and paresthesia in her legs, making it difficult to bear weight. She underwent surgery to remove a parathyroid adenoma, but unfortunately, her symptoms returned. Her magnetic resonance imaging revealed a lesion in her proximal femur, which was promptly removed. The tissue examination results verified the identity of the tumor as a PMT. The patient\'s phosphorus levels returned to normal and after a year of follow-up, she was able to resume normal daily activities, bear weight on the affected limb and showed no signs of the tumor recurrence.
UNASSIGNED: Adult patients experiencing bone pain, progressive weakness, and multiple fractures with no family history of similar conditions should consider TIO as a potential cause. It is rare and often misdiagnosed and complete surgical removal of the tumor is the optimal treatment for TIO, resulting in the resolution of long-standing symptoms and biochemical abnormalities. Timely recognition, localization, and surgical removal of the tumor are crucial for symptom resolution and the restoration of normal bone mineralization.

Phosphaturic mesenchymal tumor (PMT) is a rare disorder primarily affecting the extremities. It is notable for its correlation with hypophosphatemic osteomalacia and high FGF23 serum levels, which results in renal phosphate wasting and clinical symptoms associated with low serum phosphorus. We presented a patient with a 5-year history of progressive osteomalacia who recently experienced a major pathological bone fracture. Laboratory findings showed a persistent low serum phosphate, normal calcium, elevated alkaline phosphatase activity, high parathyroid hormone levels, and increased renal excretion of phosphate. According to ultrasonography and nuclear imaging, there was no evidence of parathyroid adenoma. During further diagnostic assessment, a sinonasal cavity tumor was found and resected. Histologically, the tumor was composed of bland spindle cell proliferation in the background of a calcified matrix with foci of osteoid formation, hemangiopericytoma-like (HPC-like) vasculature, and osteoclast-like giant cells. Tumor cells showed variable positivity for SMA, but CD34, S100, CD99, Melan-A, p63, and desmin were all nonreactive. Regarding the clinical context, histological and immunohistological findings, a final diagnosis of tumor-induced osteomalacia (TIO) secondary to a PMT was made. After surgery, laboratory results returned to normal, clinical symptoms disappeared, and the patient did not experience a recurrence during a six-month follow-up.

Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases.
A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were (\"PMT\" or \"TIO\" or \"Tumor-induced osteomalacia\" or \"phosphaturic mesenchymal tumor\") and (\"spine\" or \"spinal\"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented.
We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options.
Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect.