Skip to main content
SpringerLink
Log in

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

  • Case Reports
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  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 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Medical Disciplines, “Sapienza” University, Viale del Policlinico 155, 00161, Rome, Italy

    Luciano Colangelo, Cristiana Cipriani, Jessica Pepe, Chiara Sonato, Mirella Cilli, Walter Gianni, Federica Ferrone & Salvatore Minisola

  2. Department of Molecular Medicine, “Sapienza” University, Rome, Italy

    Alessandro Corsi

  3. Department of Radiology, Oncology and Human Pathology, “Sapienza” University, Rome, Italy

    Giulia Follacchio

  4. Department of Anatomical Sciences, Histological, Forensic Medicine and Locomotive System, “Sapienza” University, Rome, Italy

    Oreste Moreschini

  5. Radius Health, Inc., Waltham, MA, USA

    Lorraine A. Fitzpatrick

Authors
  1. Luciano Colangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristiana Cipriani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jessica Pepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandro Corsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara Sonato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giulia Follacchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mirella Cilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Walter Gianni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Federica Ferrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Oreste Moreschini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lorraine A. Fitzpatrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Salvatore Minisola
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Salvatore Minisola.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s00223-018-0429-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-018-0429-x

Keywords

Search

Navigation