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European Spine Journal

, Volume 27, Supplement 3, pp 555–560 | Cite as

Solitary juvenile xanthogranuloma in the spine pretreated with neoadjuvant denosumab therapy followed by surgical resection in a 5-year-old child: case report and literature review

  • Tero Irmola
  • Minna K. Laitinen
  • Jyrki Parkkinen
  • Jacob Engellau
  • Marko H. Neva
Case Report

Abstract

Purpose

We present a case report that describes neoadjuvant denosumab therapy initiated in a child with a solitary giant cell-rich juvenile xanthogranuloma tumor involving the spine, and review the current literature.

Methods

A giant cell-rich histiocytic lesion involving the 11th thoracic vertebral body was identified in a healthy 5-year-old girl with persistent back and pelvic pain for several months. Imaging examinations and an open biopsy were performed to obtain a definite pathologic diagnosis. As the tumor appeared to be aggressive in nature, we administered adjuvant therapy with denosumab preoperatively and then performed a total spondylectomy.

Results

Histopathology confirmed that the tumor was juvenile xanthogranuloma. No tumor metastases or recurrence were detected at the 3-year follow-up, and the patient was asymptomatic.

Conclusions

In giant cell-rich tumors, denosumab is occasionally used as neoadjuvant or adjuvant therapy, especially for tumors in difficult locations or with substantial soft tissue extensions. Rare adverse events in children include skin infections and disruption of calcium homeostasis. Surgical treatment is aimed at removing the tumor and relieving the symptomatic spinal cord compression. Use of denosumab as neoadjuvant therapy for juvenile xanthogranuloma involving the spine has not been reported previously.

Keywords

Spine Tumor Xanthogranuloma Denosumab Hypercalcemia 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Wilne S, Walker D (2010) Spine and spinal cord tumours in children: a diagnostic and therapeutic challenge to healthcare systems. Arch Dis Child Educ Pract Ed 95:47–54.  https://doi.org/10.1136/adc.2008.143214 CrossRefPubMedGoogle Scholar
  2. 2.
    Metkar U, Wardak Z, Katz DA, Lavelle WF (2012) Giant cell tumor of a lumbar vertebra in a 7-year-old child: a case report. J Pediatr Orthop 32:e76–e80.  https://doi.org/10.1097/BPO.0b013e31826193e7 CrossRefPubMedGoogle Scholar
  3. 3.
    Cao D, Ma J, Yang X, Xiao J (2008) Solitary juvenile xanthogranuloma in the upper cervical spine: case report and review of the literatures. Eur Spine J 17:318–323.  https://doi.org/10.1007/s00586-008-0606-0 CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Werner M (2006) Giant cell tumour of bone: morphological, biological and histogenetical aspects. Int Orthrop 30:484–489.  https://doi.org/10.1007/s00264-006-0215-7 CrossRefGoogle Scholar
  5. 5.
    Khalatbari MR, Moharamzad Y (2014) Brown tumor of the spine in patients with primary hyperparathyroidism. Spine 39:1073–1079.  https://doi.org/10.1097/BRS.0000000000000455 CrossRefGoogle Scholar
  6. 6.
    Schwab JH, Springfield DS, Raskin KA, Mankin HJ, Hornicek FJ (2012) What’s new in primary bone tumors. J Bone Joint Surg (Am) 94:1913.  https://doi.org/10.2106/JBJS.L.00955 CrossRefGoogle Scholar
  7. 7.
    Brosjö O, Pechon P, Hesla A, Tsagozis P, Bauer H (2013) Sclerotherapy with polidocanol for treatment of aneurysmal bone cysts. Acta Orthop 84:502–505.  https://doi.org/10.3109/17453674.2013.850013 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Konar S, Pandey P, Yasha TC (2014) Solitary juvenile xanthogranuloma in cervical spine: case report and review of the literature. Turk Neurosurg 24:102–107.  https://doi.org/10.5137/1019-5149.JTN.7712-13.0 PubMedCrossRefGoogle Scholar
  9. 9.
    Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E (2013) Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol 31:e200–e202.  https://doi.org/10.1200/JCO.2012.46.4255 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Silva-Fernández L, Rosario MP, Martínez-López JA, Carmona L, Loza E (2013) Denosumab for the treatment of osteoporosis: a systematic literature review. Reumatol Clin 9:42–52.  https://doi.org/10.1016/j.reumae.2012.06.020 CrossRefPubMedGoogle Scholar
  11. 11.
    Ford JA, Jones R, Elders A, Mulatero C, Royle P, Sharma P, Stewart F, Todd R, Mowatt G (2013) Denosumab for treatment of bone metastases secondary to solid tumours: systematic review and network meta-analysis. Eur J Cancer 49:416–430.  https://doi.org/10.1016/j.ejca.2012.07.016 CrossRefPubMedGoogle Scholar
  12. 12.
    Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S (2010) Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 11:275–280.  https://doi.org/10.1016/S1470-2045(10)70010-3 CrossRefPubMedGoogle Scholar
  13. 13.
    Gaston CL, Grimer RJ, Parry M, Stacchiotti S, Dei Tos AP, Gelderblom H, Ferrari S, Baldi GG, Jones RL, Chawla S, Casali P, LeCesne A, Blay JY, Dijkstra SP, Thomas DM, Rutkowski P (2016) Current status and unanswered questions on the use of denosumab in giant cell tumor of bone. Clin Sarcoma Res 6:15.  https://doi.org/10.1186/s13569-016-0056-0 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I (2012) Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 18:4415–4424.  https://doi.org/10.1158/1078-0432.CCR-12-0578 CrossRefPubMedGoogle Scholar
  15. 15.
    Mattei TA, Ramos E, Rehman AA, Shaw A, Patel SR, Mendel E (2014) Sustained long-term complete regression of a giant cell tumor of the spine after treatment with denosumab. Spine J 14:e15–e21.  https://doi.org/10.1016/j.spinee.2014.02.019 CrossRefPubMedGoogle Scholar
  16. 16.
    Dubory A, Missenard G, Domont J, Court C (2016) Interest of denosumab for the treatment of giant-cells tumors and aneurysmal bone cysts of the spine. About Nine Cases. Spine 41:E654–E660.  https://doi.org/10.1097/BRS.0000000000001350 CrossRefPubMedGoogle Scholar
  17. 17.
    Goldschlager T, Dea N, Boyd M, Reynolds J, Patel S, Rhines LD, Mendel E, Pacheco M, Ramos E, Mattei TA, Fisher CG (2015) Giant cell tumors of the spine: Has denosumab changed the treatment paradigm? J Neurosurg Spine 22:526–533.  https://doi.org/10.3171/2014.10.SPINE13937 CrossRefPubMedGoogle Scholar
  18. 18.
    Wang HD, Boyce AM, Tsai JY, Gafni RI, Farley FA, Kasa-Vubu JZ, Molinolo AA, Collins MT (2014) Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab 99:891–897.  https://doi.org/10.1210/jc.2013-3081 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Federman N, Brien EW, Narasimhan V, Dry SM, Sodhi M, Chawla SP (2014) Giant cell tumor of bone in childhood: clinical aspects and novel therapeutic targets. Pediatr Drugs 16:21–28.  https://doi.org/10.1007/s40272-013-0051-3 CrossRefGoogle Scholar
  20. 20.
    Lange T, Stehling C, Fröhlich B, Klingenhöfer M, Kunkel P, Schneppenheim R, Escherich G, Gosheger G, Hardes J, Jürgens H, Schulte TL (2013) Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J 22:1417–1422.  https://doi.org/10.1007/s00586-013-2715-7 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E (2012) First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact 12:183–188PubMedGoogle Scholar
  22. 22.
    Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, Bassim C, Cherman N, Ellsworth M, Kasa-Vubu JZ, Farley FA, Molinolo AA, Bhattacharyya N, Collins MT (2012) Denosumab treatment for fibrous dysplasia. J Bone Miner Res 27:1462–1470.  https://doi.org/10.1002/jbmr.1603 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Grasemann C, Schündeln MM, Hövel M, Schweiger B, Bergmann C, Herrmann R, Wieczorek D, Zabel B, Wieland R, Hauffa BP (2013) Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease. J Clin Endocrinol Metab 98:3121–3126.  https://doi.org/10.1210/jc.2013-1143 CrossRefPubMedGoogle Scholar
  24. 24.
    Shroff R, Beringer O, Rao K, Hofbauer LC, Schulz A (2012) Denosumab for post-transplantation hypercalcemia in osteopetrosis. N Engl J Med 367:1766–1767.  https://doi.org/10.1056/NEJMc1206193 CrossRefPubMedGoogle Scholar
  25. 25.
    Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze S, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I (2013) Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 14:901–908.  https://doi.org/10.1016/S1470-2045(13)70277-8 CrossRefPubMedGoogle Scholar
  26. 26.
    Miller PD (2011) A review of the efficacy and safety of denosumab in postmenopausal women with osteoporosis. Ther Adv Musculoskel Dis 3:271–282.  https://doi.org/10.1177/1759720X11424220 CrossRefGoogle Scholar
  27. 27.
    Setsu N, Kobayashi E, Asano N, Yasui N, Kawamoto H, Kawai A, Horiuchi K (2015) Severe hypercalcemia following denosumab treatment in a juvenile patient. J Bone Miner Metab 34:118–122.  https://doi.org/10.1007/s00774-015-0677-z CrossRefPubMedGoogle Scholar
  28. 28.
    Arceci RJ (1999) The histiocytoses: the fall of the Tower of Babel. Eur J Cancer 35:747–767CrossRefPubMedGoogle Scholar
  29. 29.
    Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, Bucsky P, Eqeler RM, Elinger G, Gadner H, Gresik M, Henter JI, Ilmashuku S, Janka-Schaud G, Jaffe R, Ladisch S, Nezelof C, Pritchard J (1997) Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol 29:157–166CrossRefPubMedGoogle Scholar
  30. 30.
    Freyer DR, Kennedy R, Bostrom BC, Kohut G, Dehner LP (1996) Juvenile xanthogranuloma: forms of systemic disease and their clinical implications. J Pediatr 129:227–237CrossRefPubMedGoogle Scholar
  31. 31.
    Dehner LP (2003) Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 27:579–593CrossRefPubMedGoogle Scholar
  32. 32.
    Janssen D, Harms D (2005) Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the kiel pediatric tumor registry. Am J Surg Pathol 29:21–28CrossRefPubMedGoogle Scholar
  33. 33.
    Wille D-A, Bozinov O, Scheer I, Grotzer MA, Boltshauser E (2013) Isolated intraspinal juvenile xanthogranuloma in an infant presenting as acute paraplegia. Neuropediatrics 44:171–173.  https://doi.org/10.1055/s-0032-1329908 CrossRefPubMedGoogle Scholar
  34. 34.
    Shimosawa S, Tohyama K, Shibayama M, Takeuchi H, Hirota T (1993) Spinal xanthogranuloma in a child: case report. Surg Neurol 39:138–142CrossRefPubMedGoogle Scholar
  35. 35.
    Bhaisora K, Jaiswal A, Mehrotra A, Sahu RN, Srivastava A, Jaiswal S, Behari S (2015) Solitary juvenile xanthogranuloma of the cervical spine in a child: a case report and review of literature. Asian J Neurosurg 10:57.  https://doi.org/10.4103/1793-5482.151525 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Rampini PM, Alimehmeti RH, Egidi MG, Zavanone ML, Bauer D, Fossali E, Villani RM (2001) Isolated cervical juvenile xanthogranuloma in childhood. Spine 26:1392–1395CrossRefPubMedGoogle Scholar
  37. 37.
    Kim DS, Kim TS, Choi JU (1996) Intradural extramedullary xanthoma of the spine: a rare lesion arising from the dura mater of the spine: case report. Neurosurgery 39:182–185CrossRefPubMedGoogle Scholar
  38. 38.
    Castro-Gago M, Gómez-Lado C, Alvez F, Alonso A, Vieites B (2009) Juvenile xanthogranuloma of the cauda equina. Pediatr Neurol 40:123–125.  https://doi.org/10.1016/j.pediatrneurol.2008.10.014 CrossRefPubMedGoogle Scholar
  39. 39.
    Kitchen ND, Davies MS, Taylor W (1995) Juvenile xanthogranuloma of nerve root origin. Br J Neurosurg 9:233–237.  https://doi.org/10.1080/02688699550041629 CrossRefPubMedGoogle Scholar
  40. 40.
    Abla O, Halliday W, Laughlin S, Weitzman S (2013) Central nervous system juvenile xanthogranuloma after langerhans cell histiocytosis. Pediatr Blood Cancer 60:342–343.  https://doi.org/10.1002/pbc.24379 CrossRefPubMedGoogle Scholar
  41. 41.
    Gossai N, Hilgers MV, Polgreen LE, Greengard EG (2015) Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone. Pediatr Blood Cancer 62:1078–1080.  https://doi.org/10.1002/pbc.25393 CrossRefPubMedGoogle Scholar
  42. 42.
    Sølling ASK, Harsløf T, Kaal A, Rejnmark L, Langdahl B (2016) Hypercalcemia after discontinuation of long-term denosumab treatment. Osteoporos Int 27:2383–2386.  https://doi.org/10.1007/s00198-016-3535-5 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Tero Irmola
    • 1
  • Minna K. Laitinen
    • 2
  • Jyrki Parkkinen
    • 3
  • Jacob Engellau
    • 4
  • Marko H. Neva
    • 2
  1. 1.Coxa, Hospital for Joint ReplacementTampereFinland
  2. 2.Department of Orthopedics and Traumatology, Unit of Musculoskeletal SurgeryTampere University HospitalTampereFinland
  3. 3.Fimlab LaboratoriesTampereFinland
  4. 4.Department of OncologySkane University HospitalLundSweden

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