Abstract
Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm that secretes fibroblast growth factor-23 (FGF-23) and causes oncogenic osteomalacia. It occurs in adults with equal gender distribution and the most common location is the lower extremities, followed by the head and neck. Besides osteomalacia, the clinical presentation includes bone pain and multiple bone fractures. Microscopic features consist of spindle cells, multinucleated giant cells, and calcifications embedded in a chondromyxoid matrix. Laboratory findings indicate normal calcium and parathyroid levels, hypophosphatemia, and increased levels of FGF-23 that usually revert to normal after surgical removal. Due to its rarity, the purpose of the study was to report 2 new oral cases of PMT and to review the literature in the head and neck. The first case occurred in the gingiva and had been present for 6 years. The second case was a recurrence of a previously diagnosed PMT in the right mandible that metastasized to the lung and soft tissue. The literature review included 53 cases in the head and neck. There was a predilection for extra-oral sites (76 %) compared to intra-oral sites (24 %) with paranasal sinuses considered the most common location (38 %) followed by the mandible (15 %). There were 9 recurrences that included 3 malignant cases indicating a potentially aggressive tumor. Due to the indeterminate biological behavior of PMT and its rarity, a comprehensive evaluation of medical, laboratory, radiographic, and histological findings are crucial for a definitive diagnosis and treatment.
Similar content being viewed by others
References
Koplas MC, Rubin BP, Sundaram M. Phosphaturic mesenchymal tumor: two contrasting cases. Skeletal Radiol. 2014;43(6):841–5. doi:10.1007/s00256-013-1798-x.
Ledford CK, Zelenski NA, Cardona DM, Brigman BE, Eward WC. The phosphaturic mesenchymal tumor: Why is definitive diagnosis and curative surgery often delayed? Clin Orthop Relat Res. 2013;471(11):3618–25. doi:10.1007/s11999-013-3178-1.
Woo VL, Landesberg R, Imel EA, Singer SR, Folpe AL, Econs MJ, et al. Phosphaturic mesenchymal tumor, mixed connective tissue variant, of the mandible: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(6):925–32. doi:10.1016/j.tripleo.2009.07.005.
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.
Gonzalez-Compta X, Manos-Pujol M, Foglia-Fernandez M, Peral E, Condom E, Claveguera T, et al. Oncogenic osteomalacia: case report and review of head and neck associated tumours. J Laryngol Otol. 1998;112(4):389–92.
Crouzet J, Mimoune H, Beraneck L, Juan LH. Hypophosphatemic osteomalacia with plantar neurilemoma. A review of the literature (100 cases). Revue du Rhumatisme (English ed). 1995;62(6):463–6.
Guglielmi G, Bisceglia M, Scillitani A, Folpe AL. Oncogenic osteomalacia due to phosphaturic mesenchymal tumor of the craniofacial sinuses. Clin Cases Miner Bone Metab. 2011;8(2):45–9.
Luo L, Low N, Vandervord J. Mandibular phosphaturic mesenchymal tumor-mixed connective tissue variant in a young girl. Cleft Palate Craniofac J. 2013;50(6):751–3. doi:10.1597/12-085.
Deep NL, Cain RB, McCullough AE, Hoxworth JM, Lal D. Sinonasal phosphaturic mesenchymal tumor: case report and systematic review. Allergy Rhinol. 2014;5(3):162–7. doi:10.2500/ar.2014.5.0100 (Providence, RI).
Gardner KH, Shon W, Folpe AL, Wieland CN, Tebben PJ, Baum CL. Tumor-induced osteomalacia resulting from primary cutaneous phosphaturic mesenchymal tumor: a case and review of the medical literature. J Cutan Pathol. 2013;40(9):780–4. doi:10.1111/cup.12209.
Honda R, Kawabata Y, Ito S, Kikuchi F. Phosphaturic mesenchymal tumor, mixed connective tissue type, non-phosphaturic variant: report of a case and review of 32 cases from the Japanese published work. J Dermatol. 2014;41(9):845–9. doi:10.1111/1346-8138.12602.
Salih KHSA, Montgomery EA. Selected lesions featuring giant cells. Surg Pathol. 2011;4:887–913.
Suryawanshi P, Agarwal M, Dhake R, Desai S, Rekhi B, Reddy KB, et al. Phosphaturic mesenchymal tumor with chondromyxoid fibroma-like feature: an unusual morphological appearance. Skeletal Radiol. 2011;40(11):1481–5. doi:10.1007/s00256-011-1159-6.
Kaylie DM, Jackson CG, Gardner EK. Oncogenic osteomalacia caused by phosphaturic mesenchymal tumor of the temporal bone. Otolaryngol Head Neck Surg. 2006;135(4):653–4. doi:10.1016/j.otohns.2005.03.086.
Puthenveetil PJ, Hattab EM, Peacock M, Horn EM. Thoracic phosphaturic mesenchymal tumors causing oncogenic osteomalacia. J Clin Neurosci. 2013;20(8):1057–61. doi:10.1016/j.jocn.2012.09.035.
Dupond JL, Mahammedi H, Prie D, Collin F, Gil H, Blagosklonov O, et al. Oncogenic osteomalacia: diagnostic importance of fibroblast growth factor 23 and F-18 fluorodeoxyglucose PET/CT scan for the diagnosis and follow-up in one case. Bone. 2005;36(3):375–8. doi:10.1016/j.bone.2005.01.001.
Kabtouri H, Karmali R, Spinato L, Khamaktchian M, Bisschop P. Oncogenic osteomalacia induced by a sinonasal tumour: case report and review. B-ENT. 2014;10(2):149–55.
Viscasillas G, Maiz J, Lao X, Zschaeck C, Sanz JJ. Oncogenic osteomalacia due to phosphaturic mesenchymal tumour in infratemporal fossa. Acta Otorrinolaringol Esp. 2010;61(5):392–4. doi:10.1016/j.otorri.2009.10.007.
Weidner N, Santa Cruz D. Phosphaturic mesenchymal tumors. A polymorphous group causing osteomalacia or rickets. Cancer. 1987;59(8):1442–54.
Mori Y, Ogasawara T, Motoi T, Shimizu Y, Chikazu D, Tamura K, et al. Tumor-induced osteomalacia associated with a maxillofacial tumor producing fibroblast growth factor 23: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):e57–63. doi:10.1016/j.tripleo.2009.10.052.
Hannan FM, Athanasou NA, Teh J, Gibbons CL, Shine B, Thakker RV. Oncogenic hypophosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1. Eur J Endocrinol. 2008;158(2):265–71. doi:10.1530/eje-07-0485.
Pedrazzoli M, Colletti G, Ferrari M, Rossetti G, Moneghini L, Autelitano L. Mesenchymal phosphaturic neoplasm in the maxillary sinus: a case report. Int J Oral Maxillofac Surg. 2010;39(10):1027–32. doi:10.1016/j.ijom.2010.04.039.
Okamiya T, Takahashi K, Kamada H, Hirato J, Motoi T, Fukumoto S, et al. Oncogenic osteomalacia caused by an occult paranasal sinus tumor. Auris Nasus Larynx. 2015;42(2):167–9. doi:10.1016/j.anl.2014.10.001.
Allevi F, Rabbiosi D, Mandala M, Colletti G. Mesenchymal phosphaturic tumour: early detection of recurrence. BMJ Case Rep. 2014. doi:10.1136/bcr-2013-202827.
Mathis DA, Stehel EJ Jr, Beshay JE, Mickey BE, Folpe AL, Raisanen J. Intracranial phosphaturic mesenchymal tumors: report of 2 cases. J Neurosurg. 2013;118(4):903–7. doi:10.3171/2012.12.jns12598.
Fatani HA, Sunbuli M, Lai SY, Bell D. Phosphaturic mesenchymal tumor: a report of 6 patients treated at a single institution and comparison with reported series. Ann Diagn Pathol. 2013;17(4):319–21. doi:10.1016/j.anndiagpath.2012.06.005.
Syed MI, Chatzimichalis M, Rossle M, Huber AM. Recurrent phosphaturic mesenchymal tumour of the temporal bone causing deafness and facial nerve palsy. J Laryngol Otol. 2012;126(7):721–4. doi:10.1017/s0022215112000989.
Xian-Ling W, Jian-Ming B, Wen-Wen Z, Zhao-Hui L, Jing-Tao D, Ju-Ming L, et al. Osteomalacia caused by tumors in facies cranii mimicking rheumatoid arthritis. Rheumatol Int. 2012;32(8):2573–6. doi:10.1007/s00296-011-2018-4.
Munoz J, Ortega RM, Celzo F, Donthireddy V. Tumour-induced osteomalacia. BMJ Case Rep. 2012. doi:10.1136/bcr.03.2012.5975.
Andreopoulou P, Dumitrescu CE, Kelly MH, Brillante BA, Cutler Peck CM, Wodajo FM, et al. Selective venous catheterization for the localization of phosphaturic mesenchymal tumors. J Bone Miner Res. 2011;26(6):1295–302. doi:10.1002/jbmr.316.
Uno T, Kawai K, Kunii N, Fukumoto S, Shibahara J, Motoi T, et al. Osteomalacia caused by skull base tumors: report of 2 cases. Neurosurgery. 2011;69(1):E239–44. doi:10.1227/NEU.0b013e31821867f7.
Kominek P, Starek I, Geierova M, Matousek P, Zelenik K. Phosphaturic mesenchymal tumour of the sinonasal area: case report and review of the literature. Head Neck Oncol. 2011;3:16. doi:10.1186/1758-3284-3-16.
Sidell D, Lai C, Bhuta S, Barnes L, Chhetri DK. Malignant phosphaturic mesenchymal tumor of the larynx. Laryngoscope. 2011;121(9):1860–3. doi:10.1002/lary.21916.
Peterson NR, Summerlin DJ, Cordes SR. Multiple phosphaturic mesenchymal tumors associated with oncogenic osteomalacia: case report and review of the literature. Ear Nose Throat J. 2010;89(6):E11–5.
Shelekhova KV, Kazakov DV, Michal M. Sinonasal phosphaturic mesenchymal tumor (mixed connective tissue variant): report of 2 cases. Am J Surg Pathol. 2010;34(4):596–7. doi:10.1097/PAS.0b013e3181d594fa.
Parshwanath HA, Kulkarni PR, Rao R, Joshi SK, Patil P. Phosphaturic mesenchymal tumor of ethmoid sinus. Indian J Pathol Microbiol. 2010;53(2):384. doi:10.4103/0377-4929.64317.
Winters R, Bihlmeyer S, McCahill L, Cooper K. Phosphaturic mesenchymal tumour-mixed connective tissue variant without oncogenic osteomalacia. J Clin Pathol. 2009;62(8):760–1. doi:10.1136/jcp.2008.055996.
Savage CR, Zimmer LA. Oncogenic osteomalacia from pterygopalatine fossa mass. J Laryngol Otol. 2009;123(9):1052–4. doi:10.1017/s0022215109004927.
Gupta R, Sharma A, Ksh A, Khadgawat R, Dinda AK. Phosphaturic mesenchymal tumor of the sinonasal tract. Acta Endocrinol Buchar. 2009;5(4):537–42. doi:10.4183/aeb.2009.537.
Kenealy H, Holdaway I, Grey A. Occult nasal sinus tumours causing oncogenic osteomalacia. Eur J Intern Med. 2008;19(7):516–9. doi:10.1016/j.ejim.2008.01.011.
Elston MS, Stewart IJ, Clifton-Bligh R, Conaglen JV. A case of oncogenic osteomalacia with preoperative secondary hyperparathyroidism: description of the biochemical response of FGF23 to octreotide therapy and surgery. Bone. 2007;40(1):236–41. doi:10.1016/j.bone.2006.07.027.
Koriyama N, Nishimoto K, Kodama T, Nakazaki M, Kurono Y, Yoshida H, et al. Oncogenic osteomalacia in a case with a maxillary sinus mesenchymal tumor. Am J Med Sci. 2006;332(3):142–7.
Inokuchi G, Tanimoto H, Ishida H, Sugimoto T, Yamauchi M, Miyauchi A, et al. A paranasal tumor associated with tumor-induced osteomalacia. Laryngoscope. 2006;116(10):1930–3. doi:10.1097/01.mlg.0000231295.67060.89.
Ungari C, Rocchi G, Rinna C, Agrillo A, Lattanzi A, Pagnoni M. Hypophosphaturic mesenchymal tumor of the ethmoid associated with oncogenic osteomalacia. J Craniofac Surg. 2004;15(3):523–7.
Reis-Filho JS, Paiva ME, Lopes JM. August 2003: 47-year-old female with a 7-year history of osteomalacia and hypophosphatemia. Brain pathol. 2004;14(1):111–2 (Zurich, Switzerland).
Clunie GP, Fox PE, Stamp TC. Four cases of acquired hypophosphataemic (‘oncogenic’) osteomalacia. Problems of diagnosis, treatment and long-term management. Rheumatology. 2000;39(12):1415–21 (Oxford, England).
Reyes-Mugica M, Arnsmeier SL, Backeljauw PF, Persing J, Ellis B, Carpenter TO. Phosphaturic mesenchymal tumor-induced rickets. Pediatr Dev Pathol. 2000;3(1):61–9.
David K, Revesz T, Kratimenos G, Krausz T, Crockard HA. Oncogenic osteomalacia associated with a meningeal phosphaturic mesenchymal tumor. J Neurosurg. 1996;84(2):288–92. doi:10.3171/jns.1996.84.2.0288.
Olefsky J, Kempson R, Jones H, Reaven G. “Tertiary” hyperparathyroidism and apparent “cure” of vitamin-D-resistant rickets after removal of an ossifying mesenchymal tumor of the pharynx. N Engl J Med. 1972;286(14):740–5. doi:10.1056/nejm197204062861402.
Monappa V, Naik AM, Mathew M, Rao L, Rao SK, Ramachandra L, et al. Phosphaturic mesenchymal tumour of the mandible–the useful criteria for a diagnosis on fine needle aspiration cytology. Cytopathology. 2014;25(1):54–6. doi:10.1111/cyt.12030.
Yun KI, Kim DH, Pyo SW. A phosphaturic mesenchymal tumor of the floor of the mouth with oncogenic osteomalacia: report of a case. J Oral Maxillofac Surg. 2009;67(2):402–5. doi:10.1016/j.joms.2008.01.007.
Uramoto N, Furukawa M, Yoshizaki T. Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue. Auris Nasus Larynx. 2009;36(1):104–5. doi:10.1016/j.anl.2008.01.003.
Yang IM, Park YK, Hyun YJ, Kim DY, Woo JT, Kim SW, et al. Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the oral cavity: a case report. Korean J Intern Med. 1997;12(1):89–95.
Mc CR. Osteomalacia with Looser’s nodes (Milkman’s syndrome) due to a raised resistance to vitamin D acquired about the age of 15 years. Q J Med. 1947;16(1):33–46.
Prader A, Illig R, Uehlinger E, Stalder G. Rickets following bone tumor. Helv Paediatr Acta. 1959;14:554–65.
Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004;19(3):429–35. doi:10.1359/jbmr.0301264.
Mangham DC, Kindblom LG. Rarely metastasizing soft tissue tumours. Histopathology. 2014;64(1):88–100. doi:10.1111/his.12310.
Lee JC, Jeng YM, Su SY, Wu CT, Tsai KS, Lee CH, et al. Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour. J Pathol. 2015;235(4):539–45. doi:10.1002/path.4465.
Paul S, Kurtz M, Mentzer SJ. Osteomalacia associated with a fibroblast growth factor-23 secreting chest wall tumor. J Thorac Cardiovasc Surg. 2007;134(3):803–5. doi:10.1016/j.jtcvs.2007.05.025.
Pithankuakul K, Ratanasuwan T, Thanakit V, Sukhantanak B, Kiatisevi P. Oncogenic osteomalacia caused by phosphaturic mesenchymal tumours in the proximal and shaft of the tibia: a case report. J Orthop Surg. 2014;22(2):257–62 (Hong Kong).
Bahrami A, Weiss SW, Montgomery E, Horvai AE, Jin L, Inwards CY, et al. RT-PCR analysis for FGF23 using paraffin sections in the diagnosis of phosphaturic mesenchymal tumors with and without known tumor induced osteomalacia. Am J Surg Pathol. 2009;33(9):1348–54. doi:10.1097/PAS.0b013e3181aa2311.
Uchihashi K, Nishijima-Matsunobu A, Matsuyama A, Yamasaki F, Tanabe T, Uemura T, et al. Phosphaturic mesenchymal tumor, nonphosphaturic variant, causing fatal pulmonary metastasis. Hum Pathol. 2013;44(11):2614–8. doi:10.1016/j.humpath.2013.04.027.
Sandhu FA, Martuza RL. Craniofacial hemangiopericytoma associated with oncogenic osteomalacia: case report. J Neurooncol. 2000;46(3):241–7.
Battoo AJ, Salih S, Unnikrishnan AG, Jojo A, Bahadur S, Iyer S, et al. Oncogenic osteomalacia from nasal cavity giant cell tumor. Head Neck. 2012;34(3):454–7. doi:10.1002/hed.21562.
Lamont EB, Cavaghan MK, Brockstein BE. Oncogenic osteomalacia as a harbinger of recurrent osteosarcoma. Sarcoma. 1999;3(2):95–9. doi:10.1080/13577149977712.
Giri GV, Sukumaran G, Ravindran C, Narasimman M. Giant cell tumor of the mandible. J Oral Maxillofac Pathol. 2015;19(1):108. doi:10.4103/0973-029x.157217.
Paparella ML, Olvi LG, Brandizzi D, Keszler A, Santini-Araujo E, Cabrini RL. Osteosarcoma of the jaw: an analysis of a series of 74 cases. Histopathology. 2013;63(4):551–7. doi:10.1111/his.12191.
Biernat W, Kaniuka S, Stempniewicz M, Reclawowicz D, Sworczak K. Phosphaturic mesenchymal tumor of spinal nerve in a patient with osteomalacia and multiple fractures. Acta Neuropathol. 2010;119(3):379–80. doi:10.1007/s00401-010-0648-3.
Ogose A, Hotta T, Emura I, Hatano H, Inoue Y, Umezu H, et al. Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia. Skeletal Radiol. 2001;30(2):99–103.
Houang M, Clarkson A, Sioson L, Elston MS, Clifton-Bligh RJ, Dray M, et al. Phosphaturic mesenchymal tumors show positive staining for somatostatin receptor 2A (SSTR2A). Hum Pathol. 2013;44(12):2711–8. doi:10.1016/j.humpath.2013.07.016.
Yamashita T, Konishi M, Miyake A, Inui K, Itoh N. Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. J Biol Chem. 2002;277(31):28265–70. doi:10.1074/jbc.M202527200.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None declared.
Rights and permissions
About this article
Cite this article
Qari, H., Hamao-Sakamoto, A., Fuselier, C. et al. Phosphaturic Mesenchymal Tumor: 2 New Oral Cases and Review of 53 Cases in the Head and Neck. Head and Neck Pathol 10, 192–200 (2016). https://doi.org/10.1007/s12105-015-0668-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12105-015-0668-3