Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated with tumor-induced osteomalacia involving bone and soft tissue that produces paraneoplastic hypophosphatemic osteomalacia. The common physiologic defect in this con- ditions involves an impairment in renal tubular phosphate reabsorption with a downregulation of renal 1α-hydroxylase activity, while calcium metabolism remains essentially unaffected. Microscopic features consist of spindle cells, multinucleated giant cells and calciﬁcations embedded in a chondromyxoid matrix with variable cellularity and prominent vascularity. Approximately 95% of PMTs involve the extremities and appendicular skeleton, with only 5% occurring in the head and neck region. Localization in the head and neck is pretty uncommon, nose and paranasal sinuses are preferentially affected. Due to its rarity, the purpose of thestudy wasto reportanewcaseofPMT whoselocations in temporomandibular joint was never reported in literature. Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal produce a bony tissues loss. Patients typically present with grad- neoplasm associated with tumor-induced osteomalacia (TIO), a ual muscular weakness and diffuse bone pain from pathologic paraneoplastic syndrome that manifests as renal phosphate fractures. The diagnosis is often delayed due to the nonspeciﬁc wasting caused by elevated serum FGF23. Besides osteomalacia, nature of the symptoms and lack of clinical suspicion. the clinical presentation includes bone pain and multiple bone The diagnosis is established by the ﬁnding of acquired fractures. The tumor cells produce a peptide hormone-like sub- chronic hypophosphatemia due to isolated renal phosphate stance known as ﬁbroblast growth factor 23 (FGF23), a physiologic wasting with concomitant elevated or inappropriately normal regulator of phosphate levels. FGF23 decreases proximal tubule blood levels of FGF23 and decreased or inappropriately normal reabsorption of phosphates and inhibits 1-α-hydroxylase, which 1,25-OH2-vitamin D (1,25(OH)2D). reduceslevelsof1-α, 25-dihydroxyvitamin D3. Overexpression of Locating the tumor is critical, as complete removal is cura- FGF23 by the tumor cells causes an increased excretion of phos- tive. For this purpose, a step-wise approach is recommended, phate in the urine, mobilization of calcium and phosphate from starting with a thorough medical history and physical examin- bones, and the reduction of osteoblastic activity that can lastly ation, followed by functional imaging Received: March 15, 2018. Accepted: April 24, 2018 Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com Downloaded from https://academic.oup.com/jscr/article-abstract/2018/5/rjy091/5005846 by Ed 'DeepDyve' Gillespie user on 21 June 2018 2 S. Pelo et al. Microscopic features consist of spindle cells, multinucleated giant cells (MNGCs) and calciﬁcations embedded in a chondro- myxoid matrix with variable cellularity and prominent vascu- larity. It contains ‘grungy’ calciﬁcation and MNGCs. Nuclear chromatin is relatively well dispersed and cell morphology is bland with minimal mitosis. Scattered MNGCs and areas of erythrocyte extravasation are also seen. Typically PMT behave as a benign neoplasm and malignant PMTs are uncommon, rarely metastasize and only 10% recur . PMT typically occurs in adults but pediatric cases have been reported with no signiﬁcant gender predilection. Frequently it is discovered in the soft tissues surrounding the extremities; ~95% of PMTs involve the appendicular skeleton, with only 5% occurring in the head and neck region . Historically, it has been reported that, of the PMTs located in the craniofacial region, the majority (more than 80%) are found in the nose and paranasal sinuses , jaws localization is exceptionally rare. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diag- nosis in all patients with hypophosphatemic osteomalacia. Due to its rarity, the purpose of the study was to report a new case of PMT whose locations in temporomandibular joint (TMJ) was never reported in literature. Figure 1: CT scan before surgery shows an oval-shaped formation of 3.5 cm diameter located in the left temporomandibular joint. MATERIALS AND METHODS Physical examination revealed a painful swelling located right in front of tragus and difﬁculty in mouth movements. Patient presentation Given the benignant appearance of formation we decided to In june 2017 a 62-year-old female referred to our department perform a conservative surgical approach with resection of the complaining for a painful slowly growing swelling at her left tumor and sparing of the surrounding tissues. TMJ which onset was reported 1 year before. Intraoperatively the tumor appeared encapsulated, without She had a history of long-standing progressive back pain any erosive behavior and easily cleavable from the surrounding extended to lower joints, resulting in difﬁculty moving which structures. It was located right inside the articular capsule in had started in 2012 and was treated in 2012 with NSAIDs with its superior extent and it was easily detachable from the con- poor results. A height reduction from 168 to 163 cm was also dylar head and from the glenoid fossa (Figs 2 and 3). reported by the patient. After the operation patient has recovered fast and dramatic She had already referred to a rheumatological consultation improvement of pain and mouth movement limitations were and she underwent different blood test: reported. The ﬁrst histological report showed moderately atypical car- � Hu, Yo and Ri antibodies tilaginous tissue, cells were resulted positive for S100 proteins � Amphiphysin antibodies and AE1/AE3 negative, the sample was then suggestive of a low � Anti-CV2 antibodies grade neoplasia with atypic cells. However, no clear diagnosis � Antigen Ma2 autoantibodies was made. � Anti-glutamic acid decarboxylase (GAD) autoantibody For this reason our histology department asked for a second � Onconeural antibodies EB1 opinion from a specialized center for soft tissue cytodiagnostic They results were all negative. and cytogenetic in Treviso, Italy. It resulted that resected tumor In 2014 she was given a diagnosis of osteoporosis and was was characterized by spindle cells associated to calcifying parti- placed on therapy with Cholecalciferol (1 cps/die), further ques- cles FGF23 positive. Findings were compatible with PMT (Figs 4 tioning revealed a negative family history of the heritable and 5). forms of osteomalacia. After 6 months of follow-up, the patient shows no evidence At the beginning of 2017 she referred to an Otolaryngology of recurrence or development of TMJ pathology, vertigo, tachy- department complaining about onset of vertigo associated with cardia and dyspnoea have disappeared (Fig. 6). tachycardia and dyspnoea. Additional workups revealed high levels of serum calcium and the presence of high levels of thyroglobulin, with a thyroid DISCUSSION increased in volume. A CT scan showed degenerative alterations and deformation PMT is a rare neoplasm involvingboneand soft tissue that in the superior part of left condyle, close to external acoustic produces paraneoplastic hypophosphatemic osteomalacia. meatus.The main ﬁnding was a calciﬁc oval-shaped formation It is most likely caused by a deﬁcit in renal tubular phos- of 3.5 cm diameter located in the left TMJ. Macroscopic features phate resorption in which FGF23 seems to be the main were peculiar for non-malignancy behavior. Its radiological responsible . appearance was thereby suggestive of a benignant neoforma- The biochemical derangements that characterize oncogenic tion of the articular joint (Fig. 1). osteomalacia consist of depressed levels of serum phosphate Downloaded from https://academic.oup.com/jscr/article-abstract/2018/5/rjy091/5005846 by Ed 'DeepDyve' Gillespie user on 21 June 2018 Phosphaturic mesenchymal tumor 3 Figure 2–3: How tumor looks like intraoperatively. It was located right inside the articular capsule. and 1,25-dihydroxyvitamin D3, together with elevated levels of urine phosphate. The common physiologic defect in this conditions involves an impairment in renal tubular phosphate reabsorption with a downregulation of renal 1α-hydroxylase activity, while calcium metabolism remains essentially unaffected. Laboratory investi- gations usually show normal serum levels of vitamin D3 and calcium, distinguishing these conditions from more common forms of osteomalacia like primary vitamin D deﬁciency . Since FGF23 secreted by the tumor causes 1,25-dihydroxyvi- tamin D deﬁciency, the tumor may indirectly causes secondary hyperparathyroidism that ﬁnally leads to osteomalacia. Progressive weakness, bone and muscle pain and pathologic fractures constitute typical symptoms. The only possible treatment for TIO is the surgical removal of causative tumor from the body. While these tumors are often small and not locally aggres- Figure 4–5: Deﬁnitive histological report showing grungy calciﬁcation and mul- sive, they are not encapsulated and tend to be locally inﬁltrative. tinucleated giant cells positive for S100 proteins and AE1/AE3 negative. First case of PMT was described by Weidner and Santa Cruz in 1987 . Approximately 95% of PMTs involve the extremities and appendicular skeleton, with only 5% occurring in the head and neck region. Localization in the head and neck is pretty uncommon, nose and paranasal sinuses are preferentially affected . In 2012 Quoting Jiang et al. reviewed 308 tumor-induced osteomalacia cases reported in literature between 1987 and 2011, among them ~46% of reported cases of TIO have occurred in females and 56% in males, with a mean age of 45.3 years. Their symptoms included muscle weakness/fatigue (100%), bone pain (100%), trouble walking (100%), reduced height (25/39, 64.1%) and pathological fractures (33/39, 84.6%), primarily in the ribs, vertebral bodies and femoral neck . Within the reported cases, 56% of tumors were located in the lower extremities, 5% in the upper extremities, 3% in the hip, 31% in the head (eight in mandible and maxilla, four in nasal sinus) and 5% in the thorax region. We found out that between 1972 and 2016 a total of 73 articles were produced regarding PMT in head and neck and 56 of them Figure 6: CT scan after surgery. were case report. Involvement of lower jaw is extremely rare Downloaded from https://academic.oup.com/jscr/article-abstract/2018/5/rjy091/5005846 by Ed 'DeepDyve' Gillespie user on 21 June 2018 4 S. Pelo et al. with only four cases reported in literature to date [3, 5, 7–9]and 4. Woo VL, Landesberg R, Imel EA, Singer SR, Folpe AL, Econs no report of cases affecting the TMJ was found in literature. MJ, et al. Phosphaturic mesenchymal tumor, mixed con- nective tissue variant, of the mandible: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral CONCLUSION Radiol Endod 2009;108:925–32. PMT is a rare mesenchymal tumor whose localisation in the 5. Jan De Beur SM. Tumor-induced osteomalacia. J Am Med TMJ was never reported . This case shows that this rare Assoc 2005;294:1260 doi:10.1001/jama.294.10.1260. neoplasm can be included in the differential diagnosis when 6. Dadoniene J, Miglinas M, Miltiniene D, Vajauskas D, Seinin dealing with TMJ benignant neoformations. D, Butenas P, et al. Tumour-induced osteomalacia: a litera- ture review and a case report. World J Surg Oncol 2015;14: CONFLICT OF INTEREST STATEMENT doi:10.1186/s12957-015-0763-7. 7. Reyes-Múgica M, Arnsmeier SL, Backeljauw PF, Persing J, None declared. Ellis B, Carpenter TO. Phosphaturic mesenchymal tumor- induced rickets. Pediatric Dev Pathol 2000;3:61–9. doi:10.1007/ REFERENCES s100240050008. 8. Yun KI, Kim DH, Pyo SW. A phosphaturic mesenchymal 1. Fatani HA, Sunbuli M, Lai SY, Bell D. Phosphaturic mesen- tumor of the ﬂoor of the mouth with oncogenic osteomal- chymal tumor: a report of 6 patients treated at a single acia: report of a case. J Oral and Maxillofac Surg 2009;67: institution and comparison with reported series. Ann Diagn 402–5. doi:10.1016/j.joms.2008.01.007. Pathol 2013;17:319–21. doi:10.1016/j.anndiagpath.2012.06. 9. Nomura G, Koshino Y, Morimoto H, Kida H, Nomura S, Tamai K. Vitamin D resistant hypophosphatemic osteomal- 2. Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni acia associated with osteosarcoma of the mandible: report F, Cho JY, et al. Most osteomalacia-associated mesenchy- of a case. Jpn J Med 1982;21:35–9. www.ncbi.nlm.nih.gov/ mal tumors are a single histopathologic entity. Am J Surg pubmed/6279944. Pathol 2004;28:1–30. doi:10.1097/00000478-200401000-00001. 10. Boniello R, Gasparini G, D’Amato G, Petrillo AD, Pelo S. TMJ 3. Weidner N, Cruz DS. Phosphaturic mesenchymal tumors. A metastasis: a unusual case report. Head Face Med 2008;4: polymorphous group causing osteomalacia or rickets. Cancer doi:10.1186/1746-160×-4-8. 1987;59:1442–54. doi:10.1002/1097-0142(19870415)59:83.0.co;2-q. 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Journal of Surgical Case Reports – Oxford University Press
Published: May 22, 2018
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