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A Challenging Case of Tumor-Induced Osteomalacia: Pathophysiological and Clinical Implications

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We investigated the usefulness of fibroblast growth factor 23 (FGF23) intraoperative assay to monitor tumor resection in patients with oncogenic osteomalacia. A 33-year-old man with 5 years’ history of lumbar and pelvis pain together with multiple vertebral fractures was admitted to our hospital. He was diagnosed with ankylosing spondylitis 1 year before. Laboratory investigation showed low tubular reabsorption of phosphate (0.41 mmol/L) despite chronic hypophosphatemia (0.39/L). Increased plasma values of FGF23 (673 pg/mL; n.v. < 95 pg/mL) were also observed. A full-body CT scan showed two suspicious areas in the head of the right femur and in the right tibia; however, the Octreoscan™ showed an increased uptake of the tracer only in the femur. We decided to remove first the head femur lesion and perform intraoperative FGF23 assay to confirm tumor resection; if this had been unsuccessful, we would have extended the operation to excise the second bone lesion. FGF23 basal values and 10, 60, and 225 min after excision of the femoral head were 423, 127, 56, and 30 pg/mL, respectively. The brisk fall of FGF23 values suggested that the head femur lesion was responsible for the syndrome. Histological examination revealed a mesenchymal highly vascular tumor. This is the first report showing the possibility of intraoperative FGF23 assay to monitor tumor resection in patients with tumor-induced osteomalacia.

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  1. Minisola S, Peacock M, Fukumoto S, Cipriani C, Pepe J, Tella SH, Collins MT (2017) Tumour-induced osteomalacia. Nat Rev Dis Primers 3:17044

    Article  PubMed  Google Scholar 

  2. Kumar R, Folpe AL, Mullan BP (2015) Tumor-induced osteomalacia. Transl Endocrinol Metab 7:1871

    PubMed  PubMed Central  Google Scholar 

  3. Feng J, Jiang Y, Wang O, Li M, Xing X, Huo L, Li F, Yu W, Zhong DR, Jin J, Liu Y, Qi F, Lv W, Zhou L, Meng XW, Xia WB (2017) The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J 64:675–683

    Article  PubMed  Google Scholar 

  4. Walton RJ, Bijvoet OL (1975) Nomogram for derivation of renal threshold phosphate concentration. Lancet 2:309–310

    Article  PubMed  CAS  Google Scholar 

  5. Cipriani C, Biamonte F, Costa AG, Zhang C, Biondi P, Diacinti D, Pepe J, Piemonte S, Scillitani A, Minisola S, Bilezikian JP (2015) Prevalence of kidney stones and vertebral fractures in primary hyperparathyroidism using imaging technology. J Clin Endocrinol Metab 100:1309–1315

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Pedrazzoni M, Girasole G, Bertoldo F, Bianchi G, Cepollaro C, Del Puente A, Giannini S, Gonnelli S, Maggio D, Marcocci C, Minisola S, Palummeri E, Rossini M, Sartori L, Sinigaglia L (2003) Definition of a population-specific DXA reference standard in Italian women: the Densitometric Italian Normative Study (DINS). Osteoporos Int 14:978–982

    Article  PubMed  CAS  Google Scholar 

  7. Corsi A, Ippolito E, Robey PG, Riminucci M, Boyde A (2017) Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome. Skelet Radiol 46:1435–1439

    Article  Google Scholar 

  8. Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, Econs MJ, Inwards CY, Jan de Beur SM, Mentzel T, Montgomery E, Michal M, Miettinen M, Mills SE, Reith JD, O’Connell JX, Rosenberg AE, Rubin BP, Sweet DE, Vinh TN, Wold LE, Wehrli BM, White KE, Zaino RJ, Weiss SW (2004) 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 28:1–30

    Article  PubMed  Google Scholar 

  9. Agaimy A, Michal M, Chiosea S, Petersson F, Hadravsky L, Kristiansen G, Horch RE, Schmolders J, Hartmann A, Haller F, Michal M (2017) Phosphaturic mesenchymal tumors: clinicopathologic, immunohistochemical and molecular analysis of 22 cases expanding their morphologic and immunophenotypic spectrum. Am J Surg Pathol 41:1371–1380

    Article  PubMed  Google Scholar 

  10. Tajima S, Takashi Y, Ito N, Fukumoto S, Fukuyama M (2016) ERG and FLI1 are useful immunohistochemical markers in phosphaturic mesenchymal tumors. Med Mol Morphol 49:203–209

    Article  PubMed  CAS  Google Scholar 

  11. Sahoo J, Balachandran K, Kamalanathan S, Das AK, Patro DK, Halanaik D, Badhe B (2014) Tumor(s) induced osteomalacia: a curious case of double trouble. J Clin Endocrinol Metab 99:395–398

    Article  PubMed  Google Scholar 

  12. Annamalai AK, Sampathkumar K, Kane S, Shetty NS, Kulkarni S, Rangarajan V, Purandare N, Pai PS, Mahuvakar AD, Shanthi R, Suriyakumar G, Puri V, Aram S, Gopalakrishnan C, Chelian M, Srinivasan KG, Gill AJ, Gurnell M, Clifton-Bligh R (2016) Needle(s) in the haystack-synchronous multifocal tumor-induced osteomalacia. J Clin Endocrinol Metab 101:390–393

    Article  PubMed  CAS  Google Scholar 

  13. Houang M, Clarkson A, Sioson L, Elston MS, Clifton-Bligh RJ, Dray M, Ranchere-Vince D, Decouvelaere AV, de la Fouchardiere A, Gill AJ (2013) Phosphaturic mesenchymal tumors show positive staining for somatostatin receptor 2A (SSTR2A). Hum Pathol 44:2711–2718

    Article  PubMed  CAS  Google Scholar 

  14. Ishii A, Imanishi Y, Kobayashi K, Hashimoto J, Ueda T, Miyauchi A, Koyano HM, Kaji H, Saito T, Oba K, Komatsu Y, Kurajoh M, Nagata Y, Goto H, Wakasa K, Sugimoto T, Miki T, Inaba M, Nishizawa Y (2010) The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels. Calcif Tissue Int 86:455–462

    Article  PubMed  CAS  Google Scholar 

  15. Khosravi A, Cutler CM, Kelly MH, Chang R, Royal RE, Sherry RM, Wodajo FM, Fedarko NS, Collins MT (2007) Determination of the elimination half-life of fibroblast growth factor-23. J Clin Endocrinol Metab 92:2374–2377

    Article  PubMed  CAS  Google Scholar 

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The research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Authors and Affiliations



LC, CC, JP, AC, CS, GF, MC, WG, FF, OM, and SM were involved in the diagnosis and clinical management of the patient. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work.

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Correspondence to Salvatore Minisola.

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Conflict of interest

Luciano Colangelo, Cristiana Cipriani, Jessica Pepe, Alessandro Corsi, Chiara Sonato, Giulia Follacchio, Mirella Cilli, Walter Gianni, Federica Ferrone, Oreste Moreschini, Lorraine A. Fitzpatrick and Salvatore Minisola declares that they have no conflict of interest.

Human and Animal Rights

The study was approved by our institutional review board and conducted according to the declaration of Helsinki.

Informed Consent

Informed consent was obtained from the patient included in our report.

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Colangelo, L., Cipriani, C., Pepe, J. et al. A Challenging Case of Tumor-Induced Osteomalacia: Pathophysiological and Clinical Implications. Calcif Tissue Int 103, 465–468 (2018).

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