Phosphaturic mesenchymal tumor of nose: a case report

Phosphaturic mesenchymal tumor of nose: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Phosphaturic mesenchymal tumor of nose: a case report Surinder K Singhal, Nitin Gupta This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2603602/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: To report a case of phosphaturic mesenchymal tumour of nose highlighting the diagnostic challenges involved. Case presentation : A 50 years old male who had history of multiple lower limb fractures presented with epistaxis and a vascular mass in left nasal cavity that enhanced on contrast-enhanced computed tomography (CECT), and MRI. The patient had raised serum phosphate and PTH levels. The tumour was excised endoscopically and the patient recovered completely. Conclusion :Malignant Phosphaturic mesenchymal tumors (PMTs), although rare, may behave aggressively, recur and metastasize. They are difficult to diagnose and should be kept in differential diagnosis of nasal tumours who present with osteomalacia. Phosphaturic mesenchymal tumour Malignant nasal tumour Tumour induced osteomalacia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Primary tumours may cause metastasis to the bones causing osteomalacia. Perhaps the rarest cause of osteomalacia is paraneoplastic osteomalacia, known as Tumor induced osteomalacia (TIO) or Oncogenic osteomalacia. TIO has exceptionally been reported in association with various carcinomas, but a great majority of these cases have been related to mesenchymal tumors of soft tissue or bone. Contrary to the earlier belief that any mesenchymal tumor may occasionally cause TIO, it has become clear now, that almost all cases are caused by a single morphologically and genetically distinct neoplasm, known as Phosphaturic mesenchymal tumor (PMT). 1 Evidence in favour of this was presented by a Chinese study of 144 patients all to whom had PMT. 2 Folpe et al in 2004 reviewed 29 cases of previously reported mesenchymal tumors of soft tissue and bone with associated TIO and recategorized 83% as PMT variants 3 . Ignored as a distinctive entity, it was only in 2013, that PMTs were included in the WHO Classification of Tumors of Soft Tissue and Bone 1 . PMT-associated TIO is mediated via an overproduction of FGF23, a phosphaturic hormone normally secreted by osteocytes and osteoblasts. FGF23 acts on proximal renal tubular epithelial cells by binding to the FGF receptors, leading to activation of effector proteins. An excess of FGF23 causes internalization of sodium-phosphate cotransporters, reducing renal phosphate reabsorption in the renal proximal tubules. 4 , 5 It also inhibits 1-𝜶-hydroxylase thereby reducing levels of 1-𝜶,25-hydroxy vitamin D3. 6 The resultant increase in excretion of phosphate in the urine causes mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, finally resulting in widespread osteomalacia. These neoplasms are difficult to detect, diagnosis is often delayed, and are mostly present in extremities, while in only 5% cases they occur in craniofacial region. We present a case of a 50-year-old male patient with a protracted history of limb fractures, now presenting with a bleeding nasal mass, who was diagnosed to have a PMT in the nasal cavity. Case Presentation A 50-year-old male presented to emergency department with nasal bleeding. Examination revealed a bulge on lateral nasal wall and a mass occupying the left nasal cavity. The bleed was controlled by nasal packing. The patient had a history of multiple episodes of nasal bleeding for the last 3 months. Previous medical history revealed multiple orthopedic procedures to fix fractures in his lower limbs. The patient had been bed ridden for the last 5 years due to locomotor dysfunction. He had no other sino-nasal complaints. There was no history abdominal pains or renal stones and no family history of similar complaints. Biochemical analysis revealed reduced serum phosphate levels (1.2 mg/dl), elevated parathormone(623 pg/ml) and mildly raised prostate specific antigen (PSA) of 6.9ng/ml. Serum calcium, sodium, potassium levels were normal. Prostate hypertrophy was detected on ultrasonography. There were no other significant findings on abdomen and neck sonography. Contrast enhanced- Computed Tomography (CT) showed a heterogeneously enhancing soft tissue mass measuring 6.42 cm x 3.78 cm x 4.17 cm in the left nasal cavity reaching up to the nostril anteriorly, and posteriorly up to nasopharyngeal wall, abutting hard and soft palate. (Fig. 1 ) Medial wall of left maxillary sinus and the turbinates were eroded. The mass appeared to infiltrate into the left maxillary sinus, the ethmoids and the frontal sinuses bilaterally, and was pushing into the left orbit. There was invasion into the sphenoid sinus, but posterior skull base and pituitary were preserved. Additionally, there were lytic areas in C1-C4 and C7 vertebral bodies, and spinous processes of C7, T1-T3 vertebrae, and bony skull vault, along with diffuse osteopenia. Contrast enhanced- Magnetic Resonance Imaging (MRI) revealed an expansile mass cantered in the left nasal cavity, partially extending into the left maxillary sinus.(Fig. 2 ) There was no intracranial or skull base involvement. Diffuse degenerative changes were noted in vertebral bodies. Positron Emission Tomography showed a hypermetabolic mass arising in the left sinonasal region with maximum Standardized Uptake Value of 9.01.(Fig. 3 ) Non hyper metabolic areas of sclerosis were noted at multiple sites in the axial skeleton. A provisional clinical diagnosis of sinonasal malignant tumour with distant metastasis was made. The patient was taken up for endonasal excision under general anesthesia. The tumor was found to arise from posterior septum. It had pushed the septum to right and had caused compression of the ethmoids. It was reaching the floor of the left nasal cavity, abutting the turbinate. Total excision was achieved. Maxillary and sphenoid sinuses were filled with secretions. Post-operative period was uneventful. Histopathological examination revealed haphazard, oval to spindle tumor cells arranged in sheets, with elongated nuclei, bland chromatin, inconspicuous nucleoli and ill defined eosinophilic cytoplasm, with cells embedded in collagenised to flocculant matrix. Intervening areas showed multinucleate osteoclast like giant cells. Focal vascularity with perivascular arrangement of tumour cells was seen.(Fig. 5 ) Cells showed focal nuclear positivity for vimentin.(Fig. 6 ) The features were consistent with phosphaturic mesenchymal tumour. The serum levels of phosphate gradually returned to normal range in serial measurements and the patient was discharged with calcium and phosphate supplements, with near complete fracture healing and recovery of locomotor activities. The patient has been kept under follow up for assessment of biochemical and clinical remission. The last follow-up was at 15 months of surgery and the patient had maintained normalized biochemical parameters. The nasal cavity was healed and showed no signs of recurrence, crusts, synechiae or bleeding. Follow-up CT scan didn’t show any recurrence. (Fig. 4 ) Discussion TIO was earlier believed to be potentially caused by a wide variety of mesenchymal tumours, but current consensus favors them to be a single entity now called as PMT. Roughly 450 cases of PMT have been reported in literature 7 , although the overall incidence remains unknown due to the difficulty in diagnosis. Most PMTs occur in middle-aged adults and may originate in any soft tissue or osseous location. In the soft tissues, PMT most often involves the extremities with almost half of the cases presenting in the lower extremities 8 , whereas bone tumors commonly involve the appendicular skeleton, cranial bones and paranasal sinuses 7 , 9 . PMT usually presents with symptoms related to chronic hypophosphatemia, rather than tumor related ones. Osteomalacia leads to bone pain and fractures ensue as the disease progresses. The diagnosis of TIO is often delayed by months to years with prolonged symptoms of muscle pain, progressive weakness and multiple fractures which account for most of the tumor-related morbidity 7 , 10 . The average time from symptom onset to the diagnosis of TIO was 3 years and average time to resection was 5 years in a study by Feng et al 2 . While most PMTs are benign and clinically behave in a benign fashion, recurrence may occur locally if they are incompletely excised. Complete excision results in resolution of phosphate wasting and osteomalacia. Histologically malignant PMTs are potentially aggressive leading to recurrences, distant metastasis, and unfavorable patient outcomes 7 , 9 . The imaging features of PMTs have only very recently been described in detail. On CT scans, bone lesions are typically osteolytic, show a narrow zone of transition, and commonly contain internal matrix. On MRI, they are typically T1 isointense, T2 hyperintense, and solidly enhancing, often with areas of dark T2 signal. Radionuclide scans are often particularly valuable in the detection of occult PMT of the soft tissues; as metabolically active neoplasms, they may be identified with 99mTc-Sestamibi scintigraphy, 111In-pentetreotide scintigraphy, 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT 11 . 68Ga-DOTATATE imaging has been shown to be particularly sensitive in the identification of occult tumors 12 . PMTs usually present as soft tissue or bony masses. Some of them may be calcified, others may contain hemorrhagic nodules. Microscopically, they tend to infiltrate into surrounding soft tissues and are difficult to remove with negative margins, which accounts for the high rate of local recurrence. They show hypocellular to moderately cellular proliferation of bland, spindled to stellate cells, within a vascularized stroma. The tumor cells produce a basophilic matrix, which may calcify to form crystals, and areas that look like primitive cartilage or osteoid 7 . They show positivity for vimentin, CD56, ERG, SATB2 and somatostatin receptor 2A 9 . They sometimes show limited expression of CD34, smooth muscle actin, S- 100 protein, synaptophysin and dentin matrix protein-1 7 . There is no phenotypic overlap with solitary fibrous tumor or other histologically similar tumors. This suggests it is specific disease entity and not different neoplasms that can be classified under the umbrella term of TIO. In the nasal cavities, these tumors often comprise of thick-walled blood vessels and mature adipose tissue, simulating a vascular malformation. Sinonasal PMTs require additional sampling for identification since they produce a smaller amount of calcified matrix 3 . Malignant PMTs show high nuclear grade, high cellularity, necrosis and elevated mitotic activity and typically missing matrix production 7 . Since the morphology of PMT lacks specificity and diversity, they may be easily misdiagnosed. Most PMTs are identified and resected as part of the treatment for TIO. For benign PMTs the prognosis is excellent after complete surgical resection. Radiotherapy is a supplementary option for unresectable or incompletely resected tumors. Correction of phosphate and Vit D levels is also required 13 . Our patient had a long-protracted history of multiple fractures, disability and orthopaedic interventions and remained undiagnosed till he revealed history of nasal bleeding and underwent nasal examination and biopsy from the mass. Histopathology, Immunohistochemistry and biochemical studies revealed the metabolic abnormality, and imaging was performed to access the extent of the nasal mass. We achieved complete resection in our patient, and subsequently biochemical remission, and near complete locomotor recovery. The patient has been kept on regular follow up. Conclusion TIO is the rarest cause of osteomalacia and almost all cases are caused by PMTs. These neoplasms are difficult to detect and diagnosis is often delayed. By the time the tumor is isolated, the patient may have suffered multiple fractures and severe deformities caused by weakened bones. Complete resection is the treatment of choice. Biochemical recovery after the tumor resection serves to monitor the completeness of the resection and early detection of recurrences. Malignant PMTs, although rare, may behave aggressively, recur and metastasize. Most of them, however, are benign and a complete recovery is expected after a thorough tumor removal. Declarations Ethics approval: Not applicable for case reports Consent to participate: Taken Consent for publication: Written informed consent was obtained from the patient for publication of this case and accompanying images Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Conflicts/Competing interest: Nil Funding: Nil Authors contribution: CODE: None Dr. Surinder K Singhal: Operating surgeon, revising and editing manuscript CODE: None Dr. Nitin Gupta: Manuscript writing and editing Acknowledgements: Dept of Radiodiagnosis and Pathology References Fletcher CD, Bridge JA, Hogendoorn PC, Mertens F. WHO classification of tumours of soft tissue and bone. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours. 4th ed. Lyon: IARC Press; 2013:468. Feng J, Jiang Y, Wang O, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64:675–83. Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 2004;28(1):1-30 Cai Q, Hodgson SF, Kao PC, et al. Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia. N Engl J Med. 1994;330:1645–9. Bowe AE, Finnegan R, Jan de Beur SM, et al. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001;284:977–81. Ghorbani-Aghbolaghi A, Darrow MA, Wang T. Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss. Autops Case Rep. 2017;7:32–7 Folpe AL. Phosphaturic mesenchymal tumors: A review and update. Semin Diagn Pathol. 2019;36(4):260-8 Kalil R.K. (2015) Phosphaturic Mesenchymal Tumor. In: Santini-Araujo E., Kalil R., Bertoni F., Park YK. (eds) Tumors and Tumor-Like Lesions of Bone. Springer, London. https://doi.org/10.1007/978-1-4471-6578-1_45 Agaimy A, Michal M, Chiosea S, Petersson F, Hadravsky L, Kristiansen G, et al. Phosphaturic Mesenchymal Tumors: Clinicopathologic, Immunohistochemical and Molecular Analysis of 22 Cases Expanding their Morphologic and Immunophenotypic Spectrum. Am J Surg Pathol. 2017;41(10):1371-80 Zuo QY, Wang H, Li W, Niu XH, Huang YH, Chen J, et al. Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients. BMC Musculoskelet Disord. 2017;18(1):403 Broski SM, Folpe AL, Wenger DE. Imaging features of phosphaturic mesenchymal tumors. Skeletal Radiol. 2019;48(1):119–27. Kawai S, Ariyasu H, Furukawa Y, Yamamoto R, Uraki S, Takeshima K, et al. Effective localization in tumor-induced osteomalacia using 68Ga-DOTATOC-PET/CT, venous sampling and 3T-MRI. Endocrinol Diabetes Metab Case Rep. 2017;2017:16-0005 Yoshioka K, Nagata R, Ueda M, Yamaguchi T, Konishi Y, Hosoi M,et al. Phosphaturic mesenchymal tumor with symptoms related to osteomalacia that appeared one year after tumorectomy. Intern Med. 2006;45(20):1157-60 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2603602","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":191275303,"identity":"51ed2826-318c-47ca-bf4e-180eea28fab0","order_by":0,"name":"Surinder K Singhal","email":"","orcid":"","institution":"GMCH: Government Medical College and Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Surinder","middleName":"K","lastName":"Singhal","suffix":""},{"id":191275304,"identity":"b1441e9f-6862-47bc-934b-b127f8cda096","order_by":1,"name":"Nitin Gupta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYDACZgaGAyCajb394AMgzcNHWAszWIsEH8+ZZAOQFjairAFpkZNIMJMAW0dIgzk7/8HDBRV36tgYEtIqv+bYybAxMD98dAOPFstmZobDM848k2BjOHjstuy2ZKDD2IyNc/BoMTgM1MLbdliCjbEh7bbkNmagFh42acJa/gG1MDOYFUtuqydWSwNQCxuDGePHbYeJ0mJwmOfYYck2Hp5kacZtx3nYmAn55fzBx595ag7zy89/fvDjz23V9vzszQ8f49OCAph5wCSxykGA8QcpqkfBKBgFo2DEAABBMEF1AJ0MlgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-0706-7171","institution":"Government Medical College and Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nitin","middleName":"","lastName":"Gupta","suffix":""}],"badges":[],"createdAt":"2023-02-19 06:32:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2603602/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2603602/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":35788174,"identity":"bfde648c-bb9d-4b24-a1c6-77c7254f851a","added_by":"auto","created_at":"2023-04-14 21:56:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1173869,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal CT showed a sinonasal mass occupying nasal cavity, ethmoids, frontal, maxillary and sphenoid sinus\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/abe76878545a3be2131c6532.png"},{"id":35788169,"identity":"411750f6-4ba6-41c1-bf92-3906e90b468c","added_by":"auto","created_at":"2023-04-14 21:56:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1244165,"visible":true,"origin":"","legend":"\u003cp\u003eT2-MRI pictures showing a heterogenous mass occupying the nasal cavity, ethmoids, frontal and sphenoid sinus. Secretions in the maxillary sinus bilaterally\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/e8ef80387251d2841df99096.png"},{"id":35788170,"identity":"74093266-461f-41d3-93b3-aca4306b7654","added_by":"auto","created_at":"2023-04-14 21:56:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":910236,"visible":true,"origin":"","legend":"\u003cp\u003ePET-Scan showing uptake in the sinonasal region. No distant metastatic uptakes were identified\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/325e77c749eab1c48defadc8.png"},{"id":35789093,"identity":"c5853326-4300-4364-a3e8-c3180229dece","added_by":"auto","created_at":"2023-04-14 22:04:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1132114,"visible":true,"origin":"","legend":"\u003cp\u003eAxial CT scan sections showing pre- and post-operative status of the nasal cavity\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/7e5f5a8969d0eac0a7eca391.png"},{"id":35788173,"identity":"de95b196-3623-46b1-b8f3-f0e8ee87b20a","added_by":"auto","created_at":"2023-04-14 21:56:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1542177,"visible":true,"origin":"","legend":"\u003cp\u003eHigh magnification micrograph showing spindle cells and occasional giant multinucleate cells\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/24c3a7236e69e597ab6c3f22.png"},{"id":35789920,"identity":"cd158dd9-33e0-4956-b0e4-01d5f1f27351","added_by":"auto","created_at":"2023-04-14 22:12:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1438223,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemistry showing focal positivity for vimentin\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/c64fc3fa1ddb5a6282bc8a9a.png"},{"id":41060425,"identity":"81b2c889-62bb-4b1d-9e8f-0f344c6a5be3","added_by":"auto","created_at":"2023-08-04 08:32:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6691822,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2603602/v1/3f1dc500-6aea-40aa-ae9e-c852c39294bb.pdf"}],"financialInterests":"","formattedTitle":"Phosphaturic mesenchymal tumor of nose: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary tumours may cause metastasis to the bones causing osteomalacia. Perhaps the rarest cause of osteomalacia is paraneoplastic osteomalacia, known as Tumor induced osteomalacia (TIO) or Oncogenic osteomalacia. TIO has exceptionally been reported in association with various carcinomas, but a great majority of these cases have been related to mesenchymal tumors of soft tissue or bone. Contrary to the earlier belief that any mesenchymal tumor may occasionally cause TIO, it has become clear now, that almost all cases are caused by a single morphologically and genetically distinct neoplasm, known as Phosphaturic mesenchymal tumor (PMT).\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Evidence in favour of this was presented by a Chinese study of 144 patients all to whom had PMT.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Folpe et al in 2004 reviewed 29 cases of previously reported mesenchymal tumors of soft tissue and bone with associated TIO and recategorized 83% as PMT variants\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Ignored as a distinctive entity, it was only in 2013, that PMTs were included in the WHO Classification of Tumors of Soft Tissue and Bone\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePMT-associated TIO is mediated via an overproduction of FGF23, a phosphaturic hormone normally secreted by osteocytes and osteoblasts. FGF23 acts on proximal renal tubular epithelial cells by binding to the FGF receptors, leading to activation of effector proteins. An excess of FGF23 causes internalization of sodium-phosphate cotransporters, reducing renal phosphate reabsorption in the renal proximal tubules.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e It also inhibits 1-\u0026#120630;-hydroxylase thereby reducing levels of 1-\u0026#120630;,25-hydroxy vitamin D3.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The resultant increase in excretion of phosphate in the urine causes mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, finally resulting in widespread osteomalacia.\u003c/p\u003e \u003cp\u003eThese neoplasms are difficult to detect, diagnosis is often delayed, and are mostly present in extremities, while in only 5% cases they occur in craniofacial region.\u003c/p\u003e \u003cp\u003eWe present a case of a 50-year-old male patient with a protracted history of limb fractures, now presenting with a bleeding nasal mass, who was diagnosed to have a PMT in the nasal cavity.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 50-year-old male presented to emergency department with nasal bleeding. Examination revealed a bulge on lateral nasal wall and a mass occupying the left nasal cavity. The bleed was controlled by nasal packing. The patient had a history of multiple episodes of nasal bleeding for the last 3 months. Previous medical history revealed multiple orthopedic procedures to fix fractures in his lower limbs. The patient had been bed ridden for the last 5 years due to locomotor dysfunction. He had no other sino-nasal complaints. There was no history abdominal pains or renal stones and no family history of similar complaints.\u003c/p\u003e\n\u003cp\u003eBiochemical analysis revealed reduced serum phosphate levels (1.2 mg/dl), elevated parathormone(623 pg/ml) and mildly raised prostate specific antigen (PSA) of 6.9ng/ml. Serum calcium, sodium, potassium levels were normal. Prostate hypertrophy was detected on ultrasonography. There were no other significant findings on abdomen and neck sonography.\u003c/p\u003e\n\u003cp\u003eContrast enhanced- Computed Tomography (CT) showed a heterogeneously enhancing soft tissue mass measuring 6.42 cm x 3.78 cm x 4.17 cm in the left nasal cavity reaching up to the nostril anteriorly, and posteriorly up to nasopharyngeal wall, abutting hard and soft palate. (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) Medial wall of left maxillary sinus and the turbinates were eroded. The mass appeared to infiltrate into the left maxillary sinus, the ethmoids and the frontal sinuses bilaterally, and was pushing into the left orbit. There was invasion into the sphenoid sinus, but posterior skull base and pituitary were preserved. Additionally, there were lytic areas in C1-C4 and C7 vertebral bodies, and spinous processes of C7, T1-T3 vertebrae, and bony skull vault, along with diffuse osteopenia.\u003c/p\u003e\n\u003cp\u003eContrast enhanced- Magnetic Resonance Imaging (MRI) revealed an expansile mass cantered in the left nasal cavity, partially extending into the left maxillary sinus.(Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) There was no intracranial or skull base involvement. Diffuse degenerative changes were noted in vertebral bodies.\u003c/p\u003e\n\u003cp\u003ePositron Emission Tomography showed a hypermetabolic mass arising in the left sinonasal region with maximum Standardized Uptake Value of 9.01.(Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) Non hyper metabolic areas of sclerosis were noted at multiple sites in the axial skeleton. A provisional clinical diagnosis of sinonasal malignant tumour with distant metastasis was made.\u003c/p\u003e\n\u003cp\u003eThe patient was taken up for endonasal excision under general anesthesia. The tumor was found to arise from posterior septum. It had pushed the septum to right and had caused compression of the ethmoids. It was reaching the floor of the left nasal cavity, abutting the turbinate. Total excision was achieved. Maxillary and sphenoid sinuses were filled with secretions. Post-operative period was uneventful.\u003c/p\u003e\n\u003cp\u003eHistopathological examination revealed haphazard, oval to spindle tumor cells arranged in sheets, with elongated nuclei, bland chromatin, inconspicuous nucleoli and ill defined eosinophilic cytoplasm, with cells embedded in collagenised to flocculant matrix. Intervening areas showed multinucleate osteoclast like giant cells. Focal vascularity with perivascular arrangement of tumour cells was seen.(Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e) Cells showed focal nuclear positivity for vimentin.(Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e) The features were consistent with phosphaturic mesenchymal tumour.\u003c/p\u003e\n\u003cp\u003eThe serum levels of phosphate gradually returned to normal range in serial measurements and the patient was discharged with calcium and phosphate supplements, with near complete fracture healing and recovery of locomotor activities. The patient has been kept under follow up for assessment of biochemical and clinical remission. The last follow-up was at 15 months of surgery and the patient had maintained normalized biochemical parameters. The nasal cavity was healed and showed no signs of recurrence, crusts, synechiae or bleeding. Follow-up CT scan didn\u0026rsquo;t show any recurrence. (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTIO was earlier believed to be potentially caused by a wide variety of mesenchymal tumours, but current consensus favors them to be a single entity now called as PMT. Roughly 450 cases of PMT have been reported in literature\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, although the overall incidence remains unknown due to the difficulty in diagnosis. Most PMTs occur in middle-aged adults and may originate in any soft tissue or osseous location. In the soft tissues, PMT most often involves the extremities with almost half of the cases presenting in the lower extremities\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, whereas bone tumors commonly involve the appendicular skeleton, cranial bones and paranasal sinuses \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePMT usually presents with symptoms related to chronic hypophosphatemia, rather than tumor related ones. Osteomalacia leads to bone pain and fractures ensue as the disease progresses. The diagnosis of TIO is often delayed by months to years with prolonged symptoms of muscle pain, progressive weakness and multiple fractures which account for most of the tumor-related morbidity \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. The average time from symptom onset to the diagnosis of TIO was 3 years and average time to resection was 5 years in a study by Feng et al \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile most PMTs are benign and clinically behave in a benign fashion, recurrence may occur locally if they are incompletely excised. Complete excision results in resolution of phosphate wasting and osteomalacia. Histologically malignant PMTs are potentially aggressive leading to recurrences, distant metastasis, and unfavorable patient outcomes \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe imaging features of PMTs have only very recently been described in detail. On CT scans, bone lesions are typically osteolytic, show a narrow zone of transition, and commonly contain internal matrix. On MRI, they are typically T1 isointense, T2 hyperintense, and solidly enhancing, often with areas of dark T2 signal. Radionuclide scans are often particularly valuable in the detection of occult PMT of the soft tissues; as metabolically active neoplasms, they may be identified with 99mTc-Sestamibi scintigraphy, 111In-pentetreotide scintigraphy, 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. 68Ga-DOTATATE imaging has been shown to be particularly sensitive in the identification of occult tumors \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePMTs usually present as soft tissue or bony masses. Some of them may be calcified, others may contain hemorrhagic nodules. Microscopically, they tend to infiltrate into surrounding soft tissues and are difficult to remove with negative margins, which accounts for the high rate of local recurrence. They show hypocellular to moderately cellular proliferation of bland, spindled to stellate cells, within a vascularized stroma. The tumor cells produce a basophilic matrix, which may calcify to form crystals, and areas that look like primitive cartilage or osteoid \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThey show positivity for vimentin, CD56, ERG, SATB2 and somatostatin receptor 2A \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. They sometimes show limited expression of CD34, smooth muscle actin, S- 100 protein, synaptophysin and dentin matrix protein-1 \u003csup\u003e7\u003c/sup\u003e. There is no phenotypic overlap with solitary fibrous tumor or other histologically similar tumors. This suggests it is specific disease entity and not different neoplasms that can be classified under the umbrella term of TIO.\u003c/p\u003e \u003cp\u003eIn the nasal cavities, these tumors often comprise of thick-walled blood vessels and mature adipose tissue, simulating a vascular malformation. Sinonasal PMTs require additional sampling for identification since they produce a smaller amount of calcified matrix\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMalignant PMTs show high nuclear grade, high cellularity, necrosis and elevated mitotic activity and typically missing matrix production \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Since the morphology of PMT lacks specificity and diversity, they may be easily misdiagnosed. Most PMTs are identified and resected as part of the treatment for TIO. For benign PMTs the prognosis is excellent after complete surgical resection. Radiotherapy is a supplementary option for unresectable or incompletely resected tumors. Correction of phosphate and Vit D levels is also required \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur patient had a long-protracted history of multiple fractures, disability and orthopaedic interventions and remained undiagnosed till he revealed history of nasal bleeding and underwent nasal examination and biopsy from the mass. Histopathology, Immunohistochemistry and biochemical studies revealed the metabolic abnormality, and imaging was performed to access the extent of the nasal mass. We achieved complete resection in our patient, and subsequently biochemical remission, and near complete locomotor recovery. The patient has been kept on regular follow up.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTIO is the rarest cause of osteomalacia and almost all cases are caused by PMTs. These neoplasms are difficult to detect and diagnosis is often delayed. By the time the tumor is isolated, the patient may have suffered multiple fractures and severe deformities caused by weakened bones. Complete resection is the treatment of choice. Biochemical recovery after the tumor resection serves to monitor the completeness of the resection and early detection of recurrences. Malignant PMTs, although rare, may behave aggressively, recur and metastasize. Most of them, however, are benign and a complete recovery is expected after a thorough tumor removal.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval: Not applicable for case reports\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent to participate: Taken\u003c/p\u003e\n\u003cp\u003eConsent for publication: Written informed consent was obtained from the patient for publication of this case and accompanying images\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003eConflicts/Competing interest: Nil\u003c/p\u003e\n\u003cp\u003eFunding: Nil\u003c/p\u003e\n\u003cp\u003eAuthors contribution:\u003c/p\u003e\n\u003cp\u003eCODE: None Dr. Surinder K Singhal: Operating surgeon, revising and editing manuscript\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCODE: None Dr. Nitin Gupta: \u0026nbsp;Manuscript writing and editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements: Dept of Radiodiagnosis and Pathology\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFletcher CD, Bridge JA, Hogendoorn PC, Mertens F. WHO classification of tumours of soft tissue and bone. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours. 4th ed. Lyon: IARC Press; 2013:468.\u003c/li\u003e\n \u003cli\u003eFeng J, Jiang Y, Wang O, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64:675\u0026ndash;83.\u003c/li\u003e\n \u003cli\u003eFolpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 2004;28(1):1-30\u003c/li\u003e\n \u003cli\u003eCai Q, Hodgson SF, Kao PC, et al. Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia. N Engl J Med. 1994;330:1645\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eBowe AE, Finnegan R, Jan de Beur SM, et al. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001;284:977\u0026ndash;81.\u003c/li\u003e\n \u003cli\u003eGhorbani-Aghbolaghi A, Darrow MA, Wang T. Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss. Autops Case Rep. 2017;7:32\u0026ndash;7\u003c/li\u003e\n \u003cli\u003eFolpe AL. Phosphaturic mesenchymal tumors: A review and update. Semin Diagn Pathol. 2019;36(4):260-8\u003c/li\u003e\n \u003cli\u003eKalil R.K. (2015) Phosphaturic Mesenchymal Tumor. In: Santini-Araujo E., Kalil R., Bertoni F., Park YK. (eds) Tumors and Tumor-Like Lesions of Bone. Springer, London. https://doi.org/10.1007/978-1-4471-6578-1_45\u003c/li\u003e\n \u003cli\u003eAgaimy A, Michal M, Chiosea S, Petersson F, Hadravsky L, Kristiansen G, et al. Phosphaturic Mesenchymal Tumors: Clinicopathologic, Immunohistochemical and Molecular Analysis of 22 Cases Expanding their Morphologic and Immunophenotypic Spectrum. Am J Surg Pathol. 2017;41(10):1371-80\u003c/li\u003e\n \u003cli\u003eZuo QY, Wang H, Li W, Niu XH, Huang YH, Chen J, et al. Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients. BMC Musculoskelet Disord. 2017;18(1):403\u003c/li\u003e\n \u003cli\u003eBroski SM, Folpe AL, Wenger DE. Imaging features of phosphaturic mesenchymal tumors. Skeletal Radiol. 2019;48(1):119\u0026ndash;27.\u003c/li\u003e\n \u003cli\u003eKawai S, Ariyasu H, Furukawa Y, Yamamoto R, Uraki S, Takeshima K, et al. Effective localization in tumor-induced osteomalacia using 68Ga-DOTATOC-PET/CT, venous sampling and 3T-MRI. Endocrinol Diabetes Metab Case Rep. 2017;2017:16-0005\u003c/li\u003e\n \u003cli\u003eYoshioka K, Nagata R, Ueda M, Yamaguchi T, Konishi Y, Hosoi M,et al. Phosphaturic mesenchymal tumor with symptoms related to osteomalacia that appeared one year after tumorectomy. Intern Med. 2006;45(20):1157-60\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Phosphaturic mesenchymal tumour, Malignant nasal tumour, Tumour induced osteomalacia","lastPublishedDoi":"10.21203/rs.3.rs-2603602/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2603602/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTo report a case of phosphaturic mesenchymal tumour of nose highlighting the diagnostic challenges involved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eA 50 years old male who had history of multiple lower limb fractures presented with epistaxis and a vascular mass in left nasal cavity that enhanced on contrast-enhanced computed tomography (CECT), and MRI. The patient had raised serum phosphate and PTH levels. The tumour was excised endoscopically and the patient recovered completely.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:Malignant Phosphaturic mesenchymal tumors (PMTs), although rare, may behave aggressively, recur and metastasize. They are difficult to diagnose and should be kept in differential diagnosis of nasal tumours who present with osteomalacia.\u003c/p\u003e","manuscriptTitle":"Phosphaturic mesenchymal tumor of nose: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-14 21:55:58","doi":"10.21203/rs.3.rs-2603602/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e3468632-3180-4e48-8f7d-66301d8a10b3","owner":[],"postedDate":"April 14th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-08-04T08:24:33+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-14 21:55:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2603602","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2603602","identity":"rs-2603602","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}