# Tumor-Induced Osteomalacia as a Result of a Phosphaturic Mesenchymal Tumor: Detecting Rare Origin
## 3 Discussion  
The final diagnosis in the present case was a phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). Most PMTMCTs have been discovered in middle-aged adults with no gender predilection [2]. They are mostly found at appendicular sites, while only rare cases have been reported in the oral and maxillofacial region [3], including the paranasal sinuses, mandible, intracranial localization, maxilla, and oral cavity, in descending order of prevalence [4]. Figure 4: Microscopic findings of phosphaturic mesenchymal tumor. Woven bone elements and an incomplete rim of membranous ossification were observed. Figure 3: Cut surface of the resected specimen. Among phosphaturic mesenchymal tumors (PMTs) including PMTMCT, osteoblast-like PMT, non-ossifying fibroma-like PMT, and ossifying fibroma-like PMT [15; 16; 17], over 90% of tumor-induced osteomalacia (TIO)-associated mesenchymal tumors represent a single histopathological entity, PMTMCT [3]. Histological features of PMTMCT are highly variable, representing high proliferation of spindled-shaped to stellate tumor cells with a low nuclear grade, which are embedded in myxvoid to a chondromyxoid matrix that often contains \"grungy\" calcifications. Other features include osteoclast-like giant cells, chondroblast-like cells, mature adipocytes, microcystic changes, and fibrohistiocyystic reactions, which were well observed in our case. In rare malignant PMTMCTs, sarcomatous features can be seen [3; 16; 18]. In patients with TIO, clinical symptoms and abnormal laboratory indices are usually related to the elevation of FGF23 levels. Overexpression FGF23 is secreted by a benign mesenchymal tumor, such as a PMT, which is a key mechanism for abnormal phosphate metabolism. In phosphate homeostasis, FGF23 is responsible for the development of hypophosphatemia [19; 20]. FGF23, known as a humoral phosphaturic factor referred to as phosphatonin, is a molecule that regulates phosphate pathway metabolism and homeostasis. FGF23 plays a critical role in regulating proximal renal tubular phosphate reabsorption, of which overexpression leads to phosphaturia and hypophosphatemia [19]. Additionally, it regulates the production of vitamin D metabolites by inhibiting hydroxylation of 25-hydroxyvitamin D to 1,25-dyhydroxyvitamin D [21]. These alterations eventually cause hypophosphatemia-related disorders, including rickets in children and osteomalacia in adults [15]. TIO should be distinguished from other forms associated with hypophosphatemia. These disorders include inherited and acquired forms. Among the inherited disorders are X-linked hypophosphatemic rickets (XLHR), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR) [20; 22]. Although patients with these disorders display a clinical phenotype similar to that of TIO, these conditions are typically present in childhood and are associated with deformities in the lower extremities. In making a definitive diagnosis, obtaining family history is important; furthermore, genetic testing of the dentin matrix protein 1 (DMP1), phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) gene can be useful [23; 24]. Acquired disorders include nutritional vitamin D deficiency, nutritional phosphorus deficiency or Fanconi syndrome. In patients with these disorders, there are differences in biochemical features through the laboratory investigations from those of patients with TIO [25; 26; 27]. Identification and location of the associated tumors are difficult, resulting in a delayed final diagnosis. Some studies have shown that it takes an average of 5 years from symptom onset to the final diagnosis [28]. The reasons for the delay in diagnosis are as follows. First, the causative tumors are usually small, slow-growing benign tumors. Second, the location of the tumors are non-specific. As a result, a thorough examination of the head and neck would be delayed because TIO is extremely rare in the oral and maxillofacial regions.