A female in her 50s developed a headache, collapsed and was noted to have an acute atraumatic subdural haemorrhage (SDH) requiring surgical evacuation and intracranial pressure-directed therapy. Her background included recurrent epistaxis, severe generalised bone pain and multiple insufficiency fractures and an undifferentiated autoimmune connective tissue disease. Chronic hypophosphataemia, elevated alkaline phosphatase and raised fibroblast growth factor 23 (FGF23) were also noted. An MRI head and subsequent 68Ga CT/positron emission tomography scan demonstrated an intensely avid tumour in the right ethmoid sinus, extending intracranially. Phosphate was aggressively replaced, and alfacalcidol was initiated to circumvent the effects of FGF23 on her kidneys and bone minerals. The tumour was biopsied and then definitively resected via combined endonasal and craniotomy approaches, resulting in good clinical improvement. FGF23 titre and serum phosphate both normalised leaving the diagnosis of a phosphaturic mesenchymal tumour-secreting FGF23, leading to tumour-induced osteomalacia.

UNASSIGNED: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT).
UNASSIGNED: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed.
UNASSIGNED: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3).
UNASSIGNED: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.

OBJECTIVE: The orthopedic surgical treatment strategies for patients with tumor-induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in-depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor-induced osteomalacia (TIO), whose causative tumors are located in the hip bones.
METHODS: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub-professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery-related data, perioperative changes in blood phosphorus levels, and postoperative follow-up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are shown as the means and 25th and 75th interquartile ranges.
RESULTS: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course.
CONCLUSIONS: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

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.

Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia, phosphaturia, and low serum levels of 1,25(OH)2 Vitamin D3 are secondary to a neoplasm. A 33-year-old woman presented with musculoskeletal pain and proximal myopathy with a duration of 2.5 years which was treated with Vitamin D supplements. On the basis of the biochemical tests and histopathology, she was reevaluated and found to have TIO secondary to a phosphaturic mesenchymal tumor. The tumor was resected (limb salvage with endoprosthesis), and she had no pain or weakness at followup. The case reminds the readers to consider the possibility of TIO when evaluating patients with isolated hypophosphatemia, which may lead to long-term disability and prolonged morbidity if untreated. Early recognition and diagnosis of TIO is crucial since resection of the tumor usually reverses its manifestations.

Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.

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: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders.
RESULTS: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region.
CONCLUSIONS: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.

We present a rare case of myeloid sarcoma in the stomach of an elderly woman initially diagnosed with anaemia. Myeloid sarcoma, an unusual extramedullary manifestation of acute myeloid leukaemia (AML), primarily affects lymph nodes, bones, spine and skin, with gastrointestinal involvement being infrequent. Despite normal results from the initial endoscopy, a follow-up examination after 4 months revealed multiple submucosal gastric tumours. These developments coincided with worsening of anaemia and an increase in peripheral myeloblasts. Pathological evaluation and immunohistochemical staining confirmed gastric extramedullary infiltration associated with AML. This case highlights the importance of comprehensive diagnostic processes when suspecting leukaemic transformations, especially in myelodysplastic syndrome (MDS). Due to financial constraints, additional critical studies such as cytogenetics and next-generation sequencing were not performed. Nonetheless, this rare case demonstrates the visual observation of rapid progression from MDS to AML and concurrent early myeloid sarcoma development in an elderly patient.

BACKGROUND: Phosphaturic Mesenchymal Tumors (PMTs) are rare mesenchymal neoplasms known for producing Tumor-induced Osteomalacia (TIO). TIO is an uncommon paraneoplastic syndrome characterized by radiographic evidence of inadequate bone mineralization and analytical abnormalites.
METHODS: We sought to present a case of TIO caused by skull base PMT with intracranial extension, manifesting with pain, progressive weakness, and multiple bone fractures. Furthermore, a systematic review was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A search was conducted in PubMed database with title/abstract keywords \"Phosphaturic mesenchymal tumor\" and \"Osteomalacia.\" Search results were reviewed looking for intracranial or skull base tumors.
RESULTS: Our systematic review included 29 reported cases of intracranial PMT. In the reviewed cases there was a significative female predominance with 22 cases (75,86%). Osteomalacia was presented in 25 cases (86,20%). Bone fractures were present in 10 cases (34,48%). The most common site of involvement was the anterior cranial fossa in 14 cases (48,27%). Surgery was performed in 27 cases (93,10%) with previous tumor embolization in 4 cases (13,79%). Total recovery of the presenting symptoms in the first year was achieved in 21 cases (72,41%). Recurrence of the disease was described in 6 cases (25%).
CONCLUSIONS: Skull base PMTs with intracranial extension are extremely rare tumors. Most patients are middle-aged adults with a PMT predominantly located in anterior cranial fossa. Surgery is the current treatment of choice with optimal outcome at 1-year follow-up, although recurrence could be present in almost 25% of the cases.