Soft Tissue Special Issue: Giant Cell-Rich Lesions of the Head and Neck Region


Giant cell-rich lesions represent a heterogeneous group of tumors and non-neoplastic lesions, usually arising in bone, which harbor varying number of reactive osteoclastic-type multinucleate giant cells as a common feature. Among these entities, some are confined to the head and neck region (e.g., central giant cell granuloma and mimicking lesions, i.e., peripheral giant cell granuloma and cherubism) or show a relative predilection for this region (e.g., aneurysmal bone cyst and brown tumor of hyperparathyroidism), while others are rare but associated with distinct underlying disease (e.g., giant cell tumor of bone) or histology (e.g., tenosynovial giant cell tumor of the temporomandibular joint and phosphaturic mesenchymal tumor of the jaws) when occurring in the head and neck. Collectively, these lesions pose great challenge in the pathologic diagnosis, which often requires combinatory assessment from the clinical, histopathologic, and/or molecular aspects. This review provides a summary of pertinent clinical and pathologic features and an update of recent molecular and genetic findings of these entities. The considerations in differential diagnosis as well as the effects of the emerging therapeutic RANKL-antagonizing antibody denosumab will also be addressed.

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  1. 1.

    Athanasou NA, Bansal M, Forsyth R, Reid RP, Sapi Z. Giant cell tumour of bone. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. World Health Organization classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. p. 321–4.

  2. 2.

    Dahlin DC, Cupps RE, Johnson EW Jr. Giant-cell tumor: a study of 195 cases. Cancer. 1970;25(5):1061–70.

  3. 3.

    Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69(1):106–14.

  4. 4.

    Unni KK, Inwards CY. Dahlin’s bone tumors. 6th ed. Philadelphia: LWW; 2010.

  5. 5.

    Huvos AG. Bone tumors: diagnosis, treatment, and prognosis. 2nd ed. Philadelphia: WB Saunders; 1991.

  6. 6.

    Bertoni F, Unni KK, Beabout JW, Ebersold MJ. Giant cell tumor of the skull. Cancer. 1992;70(5):1124–32.

  7. 7.

    Czerniak B. Dorfman and Czerniak’s bone tumors. 2nd ed. Philadelphia: Saunders; 2016.

  8. 8.

    Wieneke JA, Gannon FH, Heffner DK, Thompson LD. Giant cell tumor of the larynx: a clinicopathologic series of eight cases and a review of the literature. Mod Pathol. 2001;14(12):1209–15.

  9. 9.

    Vigorita VJ. Orthopaedic pathology. 3rd ed. Philadelphia: LWW; 2016.

  10. 10.

    Zheng MH, Robbins P, Xu J, Huang L, Wood DJ, Papadimitriou JM. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. Histol Histopathol. 2001;16(1):297–307.

  11. 11.

    Wuelling M, Engels C, Jesse N, Werner M, Kaiser E, Delling G. Histogenesis of giant cell tumors. Pathologe. 2002;23(5):332–9.

  12. 12.

    Lau YS, Sabokbar A, Gibbons CL, Giele H, Athanasou N. Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue. Hum Pathol. 2005;36(9):945–54.

  13. 13.

    Meis JM, Dorfman HD, Nathanson SD, Haggar AM, Wu KK. Primary malignant giant cell tumor of bone: “dedifferentiated” giant cell tumor. Mod Pathol. 1989;2(5):541–6.

  14. 14.

    Brien EW, Mirra JM, Kessler S, Suen M, Ho JK, Yang WT. Benign giant cell tumor of bone with osteosarcomatous transformation (“dedifferentiated” primary malignant GCT): report of two cases. Skelet Radiol. 1997;26(4):246–55.

  15. 15.

    Wojcik J, Rosenberg AE, Bredella MA, Choy E, Hornicek FJ, Nielsen GP, et al. Denosumab-treated Giant cell tumor of bone exhibits morphologic overlap with malignant giant cell tumor of bone. Am J Surg Pathol. 2016;40(1):72–80.

  16. 16.

    Chan J, Gannon FH, Thompson LD. Malignant giant cell tumor of the sphenoid. Ann Diagn Pathol. 2003;7(2):100–5.

  17. 17.

    Karamanakos PN, Jaaskelainen JE, Alafuzoff I, Pirinen E, Vanninen R, Silvennoinen S, et al. Malignant giant cell tumor in the posterior fossa of a neonate. J Neurosurg Pediatr. 2010;5(3):277–82.

  18. 18.

    Vivero RJ, Dave SP, Gomez CR, Weed DT. Giant cell tumor of the larynx: a case of malignant sarcomatous transformation. Ear Nose Throat J. 2013;92(6):E59.

  19. 19.

    Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, et al. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013;45(12):1479–82.

  20. 20.

    Cleven AH, Hocker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen AM, Bovee JV. Mutation analysis of H3F3A and H3F3B as a diagnostic tool for giant cell tumor of bone and chondroblastoma. Am J Surg Pathol. 2015;39(11):1576–83.

  21. 21.

    Al-Ibraheemi A, Inwards CY, Zreik RT, Wenger DE, Jenkins SM, Carter JM, et al. Histologic spectrum of giant cell tumor (GCT) of bone in patients 18 years of age and below: a study of 63 patients. Am J Surg Pathol. 2016;40:1702–12.

  22. 22.

    Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, et al. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2016;69(3):240–7.

  23. 23.

    Amary F, Berisha F, Ye H, Gupta M, Gutteridge A, Baumhoer D, et al. H3F3A (Histone 3.3) G34W Immunohistochemistry: a reliable marker defining benign and malignant giant cell tumor of bone. Am J Surg Pathol. 2017;41(8):1059–68.

  24. 24.

    Yamamoto H, Iwasaki T, Yamada Y, Matsumoto Y, Otsuka H, Yoshimoto M, et al. Diagnostic utility of histone H3.3 G34W, G34R, and G34V mutant-specific antibodies for giant cell tumors of bone. Hum Pathol. 2018;73:41–50.

  25. 25.

    Yoshida KI, Nakano Y, Honda-Kitahara M, Wakai S, Motoi T, Ogura K, et al. Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone. Mod Pathol. 2019;32:1751–61.

  26. 26.

    Vergel De Dios AM, Bond JR, Shives TC, McLeod RA, Unni KK. Aneurysmal bone cyst. A clinicopathologic study of 238 cases. Cancer. 1992;69(12):2921–31.

  27. 27.

    Bataineh AB. Aneurysmal bone cysts of the maxilla: a clinicopathologic review. J Oral Maxillofac Surg. 1997;55(11):1212–6.

  28. 28.

    Mankin HJ, Hornicek FJ, Ortiz-Cruz E, Villafuerte J, Gebhardt MC. Aneurysmal bone cyst: a review of 150 patients. J Clin Oncol. 2005;23(27):6756–62.

  29. 29.

    Fennessy BG, Vargas SO, Silvera MV, Ohlms LA, McGill TJ, Healy GB, et al. Paediatric aneurysmal bone cysts of the head and neck. J Laryngol Otol. 2009;123(6):635–41.

  30. 30.

    Song W, Suurmeijer AJH, Bollen SM, Cleton-Jansen AM, Bovee J, Kroon HM. Soft tissue aneurysmal bone cyst: six new cases with imaging details, molecular pathology, and review of the literature. Skelet Radiol. 2019;48(7):1059–67.

  31. 31.

    Li HR, Tai CF, Huang HY, Jin YT, Chen YT, Yang SF. USP6 gene rearrangement differentiates primary paranasal sinus solid aneurysmal bone cyst from other giant cell-rich lesions: report of a rare case. Hum Pathol. 2018;76:117–21.

  32. 32.

    Sanerkin NG, Mott MG, Roylance J. An unusual intraosseous lesion with fibroblastic, osteoclastic, osteoblastic, aneurysmal and fibromyxoid elements “Solid” variant of aneurysmal bone cyst. Cancer. 1983;51(12):2278–86.

  33. 33.

    Bertoni F, Bacchini P, Capanna R, Ruggieri P, Biagini R, Ferruzzi A, et al. Solid variant of aneurysmal bone cyst. Cancer. 1993;71(3):729–34.

  34. 34.

    Martinez V, Sissons HA. Aneurysmal bone cyst. A review of 123 cases including primary lesions and those secondary to other bone pathology. Cancer. 1988;61(11):2291–304.

  35. 35.

    Gnepp D. Diagnostic surgical pathology of the head and neck. 2nd ed. Philadelphia: Saunders; 2009.

  36. 36.

    Oliveira AM, Perez-Atayde AR, Inwards CY, Medeiros F, Derr V, Hsi BL, et al. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol. 2004;165(5):1773–80.

  37. 37.

    Dal Cin P, Kozakewich HP, Goumnerova L, Mankin HJ, Rosenberg AE, Fletcher JA. Variant translocations involving 16q22 and 17p13 in solid variant and extraosseous forms of aneurysmal bone cyst. Genes Chromosomes Cancer. 2000;28(2):233–4.

  38. 38.

    Blackburn PR, Davila JI, Jackson RA, Fadra N, Atiq MA, Pitel BA, et al. RNA sequencing identifies a novel USP9X-USP6 promoter swap gene fusion in a primary aneurysmal bone cyst. Genes Chromosomes Cancer. 2019;58(8):589–94.

  39. 39.

    Oliveira AM, Chou MM. The TRE17/USP6 oncogene: a riddle wrapped in a mystery inside an enigma. Front Biosci (Schol Ed). 2012;4:321–34.

  40. 40.

    Chrcanovic BR, Gomes CC, Gomez RS. Central giant cell lesion of the jaws: an updated analysis of 2270 cases reported in the literature. J Oral Pathol Med. 2018;47(8):731–9.

  41. 41.

    Vered M, Buchner A, Dayan D. Central giant cell granuloma of the jawbones–new insights into molecular biology with clinical implications on treatment approaches. Histol Histopathol. 2008;23(9):1151–60.

  42. 42.

    Gomes CC, Gayden T, Bajic A, Harraz OF, Pratt J, Nikbakht H, et al. TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw. Nat Commun. 2018;9(1):4572.

  43. 43.

    Baumhoer D, Kovac M, Sperveslage J, Ameline B, Strobl AC, Krause A, et al. Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone. J Pathol. 2019;248(1):116–22.

  44. 44.

    Mangion J, Rahman N, Edkins S, Barfoot R, Nguyen T, Sigurdsson A, et al. The gene for cherubism maps to chromosome 4p16.3. Am J Hum Genet. 1999;65(1):151–7.

  45. 45.

    Flanagan AM, Speight PM. Giant cell lesions of the craniofacial bones. Head Neck Pathol. 2014;8(4):445–53.

  46. 46.

    Boland JM, Folpe AL, Hornick JL, Grogg KL. Clusterin is expressed in normal synoviocytes and in tenosynovial giant cell tumors of localized and diffuse types: diagnostic and histogenetic implications. Am J Surg Pathol. 2009;33(8):1225–9.

  47. 47.

    Al-Ibraheemi A, Ahrens WA, Fritchie K, Dong J, Oliveira AM, Balzer B, et al. Malignant tenosynovial giant cell tumor: the true “Synovial Sarcoma?” A clinicopathologic, immunohistochemical, and molecular cytogenetic study of 10 cases, supporting origin from synoviocytes. Mod Pathol. 2019;32(2):242–51.

  48. 48.

    Verspoor FGM, Mastboom MJL, Weijs WLJ, Koetsveld AC, Schreuder HWB, Flucke U. Treatments of tenosynovial giant cell tumours of the temperomandibular joint: a report of three cases and a review of literature. Int J Oral Maxillofac Surg. 2018;47(10):1288–94.

  49. 49.

    Cho JM, Chang JH, Kim SH, Lee KS. Pediatric giant cell tumor of the tendon sheath of the craniocervical junction involving the occipital condyle. Childs Nerv Syst. 2016;32(1):175–9.

  50. 50.

    Gelinne A, Akture E, Tranmer B. Tenosynovial giant cell tumor of the clinoid: rare condition. World Neurosurg. 2018;118:168–71.

  51. 51.

    Mastboom MJL, Verspoor FGM, Verschoor AJ, Uittenbogaard D, Nemeth B, Mastboom WJB, et al. Higher incidence rates than previously known in tenosynovial giant cell tumors. Acta Orthop. 2017;88(6):688–94.

  52. 52.

    Romanach MJ, Brasileiro BF, Leon JE, Alves DB, de Almeida OP, Vargas PA. Pigmented villonodular synovitis of the temporomandibular joint: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111(3):e17–28.

  53. 53.

    Chow LT, Kumta SM, King WW. Extra-articular pigmented villonodular synovitis of the temporomandibular joint. J Laryngol Otol. 1998;112(2):182–5.

  54. 54.

    Carlson ML, Osetinsky LM, Alon EE, Inwards CY, Lane JI, Moore EJ. Tenosynovial giant cell tumors of the temporomandibular joint and lateral skull base: review of 11 cases. Laryngoscope. 2017;127(10):2340–6.

  55. 55.

    Safaee M, Oh T, Sun MZ, Parsa AT, McDermott MW, El-Sayed IH, et al. Pigmented villonodular synovitis of the temporomandibular joint with intracranial extension: a case series and systematic review. Head Neck. 2015;37(8):1213–24.

  56. 56.

    Herman CR, Swift JQ, Schiffman EL. Pigmented villonodular synovitis of the temporomandibular joint with intracranial extension: a case and literature review. Int J Oral Maxillofac Surg. 2009;38(7):795–801.

  57. 57.

    Murphey MD, Rhee JH, Lewis RB, Fanburg-Smith JC, Flemming DJ, Walker EA. Pigmented villonodular synovitis: radiologic-pathologic correlation. Radiographics. 2008;28(5):1493–518.

  58. 58.

    Wang JG, Liu J, He B, Gao L, Zhang L, Liu J. Diffuse tenosynovial giant cell tumor around the temporomandibular joint: an entity with special radiologic and pathologic features. J Oral Maxillofac Surg. 2019;77(5):1022e1-e39.

  59. 59.

    Cai XY, Yang C, Chen MJ, Yun B. Simultaneous pigmented villonodular synovitis and synovial chondromatosis of the temporomandibular joint: case report. Int J Oral Maxillofac Surg. 2009;38(11):1215–8.

  60. 60.

    Oda Y, Izumi T, Harimaya K, Segawa Y, Ishihara S, Komune S, et al. Pigmented villonodular synovitis with chondroid metaplasia, resembling chondroblastoma of the bone: a report of three cases. Mod Pathol. 2007;20(5):545–51.

  61. 61.

    Kurt AM, Unni KK, Sim FH, McLeod RA. Chondroblastoma of bone. Hum Pathol. 1989;20(10):965–76.

  62. 62.

    Hoch BL, Garcia RA, Smalberger GJ. Chondroid tenosynovial giant cell tumor: a clinicopathological and immunohistochemical analysis of 5 new cases. Int J Surg Pathol. 2011;19(2):180–7.

  63. 63.

    Yoon HJ, Cho YA, Lee JI, Hong SP, Hong SD. Malignant pigmented villonodular synovitis of the temporomandibular joint with lung metastasis: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111(5):e30–6.

  64. 64.

    Bertoni F, Unni KK, Beabout JW, Sim FH. Malignant giant cell tumor of the tendon sheaths and joints (malignant pigmented villonodular synovitis). Am J Surg Pathol. 1997;21(2):153–63.

  65. 65.

    Li CF, Wang JW, Huang WW, Hou CC, Chou SC, Eng HL, et al. Malignant diffuse-type tenosynovial giant cell tumors: a series of 7 cases comparing with 24 benign lesions with review of the literature. Am J Surg Pathol. 2008;32(4):587–99.

  66. 66.

    West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci USA. 2006;103(3):690–5.

  67. 67.

    Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O’Connell JX, Huntsman D, et al. Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007;31(6):970–6.

  68. 68.

    Mastboom MJL, Hoek DM, Bovee J, van de Sande MAJ, Szuhai K. Does CSF1 overexpression or rearrangement influence biological behaviour in tenosynovial giant cell tumours of the knee? Histopathology. 2019;74(2):332–40.

  69. 69.

    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.

  70. 70.

    Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA. 2001;98(11):6500–5.

  71. 71.

    Boland JM, Tebben PJ, Folpe AL. Phosphaturic mesenchymal tumors: what an endocrinologist should know. J Endocrinol Invest. 2018;41(10):1173–84.

  72. 72.

    Hodgson SF, Clarke BL, Tebben PJ, Mullan BP, Cooney WP 3rd, Shives TC. Oncogenic osteomalacia: localization of underlying peripheral mesenchymal tumors with use of Tc 99m sestamibi scintigraphy. Endocr Pract. 2006;12(1):35–42.

  73. 73.

    Shih YH, Chen HC, Liao SC, Tseng MC, Lee MB. Psychotic disorder due to phosphaturic mesenchymal tumor with mixed connective tissue variant. Psychosomatics. 2012;53(1):96–7.

  74. 74.

    Garcia CA, Spencer RP. Bone and In-111 octreotide imaging in oncogenic osteomalacia: a case report. Clin Nucl Med. 2002;27(8):582–3.

  75. 75.

    Siegel HJ, Rock MG. Occult phosphaturic mesenchymal tumor detected by Tc-99m sestamibi scan. Clin Nucl Med. 2002;27(8):608–9.

  76. 76.

    El-Maouche D, Sadowski SM, Papadakis GZ, Guthrie L, Cottle-Delisle C, Merkel R, et al. (68)Ga-DOTATATE for tumor localization in tumor-induced osteomalacia. J Clin Endocrinol Metab. 2016;101(10):3575–81.

  77. 77.

    Sundaram M, McCarthy EF. Oncogenic osteomalacia. Skelet Radiol. 2000;29(3):117–24.

  78. 78.

    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.

  79. 79.

    Weidner N, Santa Cruz D. Phosphaturic mesenchymal tumors. A polymorphous group causing osteomalacia or rickets. Cancer. 1987;59(8):1442–54.

  80. 80.

    Shelekhova KV, Kazakov DV, Hes O, Treska V, Michal M. Phosphaturic mesenchymal tumor (mixed connective tissue variant): a case report with spectral analysis. Virchows Arch. 2006;448(2):232–5.

  81. 81.

    Ogose A, Hotta T, Emura I, Hatano H, Inoue Y, Umezu H, et al. Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia. Skelet Radiol. 2001;30(2):99–103.

  82. 82.

    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.

  83. 83.

    Wu H, Bui MM, Zhou L, Li D, Zhang H, Zhong D. Phosphaturic mesenchymal tumor with an admixture of epithelial and mesenchymal elements in the jaws: clinicopathological and immunohistochemical analysis of 22 cases with literature review. Mod Pathol. 2019;32(2):189–204.

  84. 84.

    Agaimy A, Michal M, Chiosea S, Petersson F, Hadravsky L, Kristiansen G, et al. Phosphaturic mesenchymal tumors: clinicopathologic, immunohistochemical and molecular analysis of 22 cases expanding their morphologic and immunophenotypic spectrum. Am J Surg Pathol. 2017;41(10):1371–80.

  85. 85.

    Yamada Y, Kinoshita I, Kenichi K, Yamamoto H, Iwasaki T, Otsuka H, et al. Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant. Histopathology. 2018;72(3):460–71.

  86. 86.

    Lee JC, Su SY, Changou CA, Yang R-S, Tsai K-S, Collins MT, et al. Characterization of FN1-FGFR1 and Novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors. Mod Pathol. 2016;29(11):1335–46.

  87. 87.

    Tajima S, Fukayama M. Fibroblast growth factor receptor 1 (FGFR1) expression in phosphaturic mesenchymal tumors. Int J Clin Exp Pathol. 2015;8(8):9422–7.

  88. 88.

    Carter JM, Caron BL, Dogan A, Folpe AL. A novel chromogenic in situ hybridization assay for FGF23 mRNA in phosphaturic mesenchymal tumors. Am J Surg Pathol. 2015;39(1):75–83.

  89. 89.

    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.

  90. 90.

    Grulois V, Buysschaert I, Schoenaers J, Debruyne F, Delaere P, Vander Poorten V. Brown tumour: presenting symptom of primary hyperparathyroidism. B-ENT. 2005;1(4):191–5.

  91. 91.

    Hong WS, Sung MS, Chun KA, Kim JY, Park SW, Lee KH, et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases. Skelet Radiol. 2011;40(2):205–13.

  92. 92.

    Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18(16):4415–24.

  93. 93.

    Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr Opin Oncol. 2012;24(4):397–403.

  94. 94.

    Stagner AM, Sajed DP, Nielsen GP, Ebb DH, Faquin WC, Chebib I, et al. Giant cell lesions of the maxillofacial skeleton express RANKL by RNA in situ hybridization regardless of histologic pattern. Am J Surg Pathol. 2019;43(6):819–26.

  95. 95.

    Won KY, Kalil RK, Kim YW, Park YK. RANK signalling in bone lesions with osteoclast-like giant cells. Pathology. 2011;43(4):318–21.

  96. 96.

    O’Connell JE, Bowe C, Murphy C, Toner M, Kearns GJ. Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(5):e191–8.

  97. 97.

    Schreuder WH, Coumou AW, Kessler PA, de Lange J. Alternative pharmacologic therapy for aggressive central giant cell granuloma: denosumab. J Oral Maxillofac Surg. 2014;72(7):1301–9.

  98. 98.

    Palmerini E, Ruggieri P, Angelini A, Boriani S, Campanacci D, Milano GM, et al. Denosumab in patients with aneurysmal bone cysts: a case series with preliminary results. Tumori. 2018;104(5):344–51.

  99. 99.

    Kurucu N, Akyuz C, Ergen FB, Yalcin B, Kosemehmetoglu K, Ayvaz M, et al. Denosumab treatment in aneurysmal bone cyst: evaluation of nine cases. Pediatr Blood Cancer. 2018.

  100. 100.

    Florenzano P, Gafni RI, Collins MT. Tumor-induced osteomalacia. Bone Rep. 2017;7:90–7.

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The authors thank Drs. Yu-Chien Kao, Wan-Shan Li, Chih-Hsueh Chen, and Yo-Chun Lin for providing kind assistance and precious cases.


This work was not supported by any research fund.

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Lee, J., Huang, H. Soft Tissue Special Issue: Giant Cell-Rich Lesions of the Head and Neck Region. Head and Neck Pathol (2020).

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  • Giant cell tumor of bone
  • Aneurysmal bone cyst
  • Central giant cell granuloma
  • Tenosynovial giant cell tumor
  • Phosphaturic mesenchymal tumor
  • Brown tumor of hyperparathyroidism