Molecular Markers of Fibro-Osseous Lesions and Osteosarcomas of the Craniofacial Complex—Current Situation and Recent Advances

Papers of particular interest, published recently, have been highlighted as: • Of importance

1. 1.
   Voytek TM, Ro JY, Edeiken J, et al. Fibrous dysplasia and cemento-ossifying fibroma. A histologic spectrum. Am J Surg Pathol. 1995;19(7):775–81.Google Scholar
2. 2.
   Slootweg PJ. Maxillofacial fibro-osseous lesions: classification and differential diagnosis. Semin Diagn Pathol. 1996;13(2):104–12.Google Scholar
3. 3.
   Franceschina MJ, Hankin RC, Irwin RB. Low-grade central osteosarcoma resembling fibrous dysplasia. A report of two cases. Am J Orthop. 1997;26(6):432–40.PubMedGoogle Scholar
4. 4.
   Muramatsu K, Hashimoto T, Seto S, et al. Low-grade central osteosarcoma mimicking fibrous dysplasia: a report of two cases. Arch Orthop Trauma Surg. 2008;128(1):11–5.Google Scholar
5. 5.
   Alawi F. Benign fibro-osseous diseases of the maxillofacial bones. A review and differential diagnosis. Am J Clin Pathol. 2002;118(Suppl):S50–70.PubMedGoogle Scholar
6. 6.
   DiCaprio MR, Enneking WF. Fibrous dysplasia. Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005;87(8):1848–64.CrossRefPubMedGoogle Scholar
7. 7.
   Toyosawa S, Yuki M, Kishino M, et al. Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol. 2007;20(3):389–96.Google Scholar
8. 8.
   Suarez-Soto A, Baquero-Ruiz de la Hermosa MC, Minguez-Martinez I, et al. Management of fibro-osseous lesions of the craniofacial area. Presentation of 19 cases and review of the literature. Med Oral Patol Oral Cir Bucal. 2013;18(3):e479–85.Google Scholar
9. 9.
   Weinstein LS, Shenker A, Gejman PV, et al. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. 1991;325(24):1688–95.Google Scholar
10. 10.
    Shenker A, Weinstein LS, Sweet DE, et al. An activating Gs alpha mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome. J Clin Endocrinol Metab. 1994;79(3):750–5.Google Scholar
11. 11.
    Alman BA, Greel DA, Wolfe HJ. Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res. 1996;14(2):311–5.CrossRefPubMedGoogle Scholar
12. 12.
    Marie PJ, de Pollak C, Chanson P, et al, Increased proliferation of osteoblastic cells expressing the activating Gs alpha mutation in monostotic and polyostotic fibrous dysplasia. Am J Pathol. 1997;150(3):1059–69.Google Scholar
13. 13.
    Sakamoto A, Oda Y, Iwamoto Y, et al. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to expressions of c-fos and c-jun products and bone matrix proteins: a clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I collagen, osteonectin, osteopontin, and osteocalcin. Hum Pathol. 1999;30(12):1418–26.Google Scholar
14. 14.
    Happle R. The McCune-Albright syndrome: a lethal gene surviving by mosaicism. Clin Genet. 1986;29(4):321–4.CrossRefPubMedGoogle Scholar
15. 15.
    Bianco P, Kuznetsov SA, Riminucci M, et al. Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gsalpha-mutated skeletal progenitor cells. J Clin Invest. 1998;101(8):1737–44.Google Scholar
16. 16.
    Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci U S A. 1992;89(11):5152–6.CrossRefPubMedPubMedCentralGoogle Scholar
17. 17.
    Okamoto S, Hisaoka M, Ushijima M, et al. Activating Gs(alpha) mutation in intramuscular myxomas with and without fibrous dysplasia of bone. Virchows Arch. 2000;437(2):133–7.Google Scholar
18. 18.
    Matsuzaka K, Shimono M, Uchiyama T, et al. Lesions related to the formation of bone, cartilage or cementum arising in the oral area: a statistical study and review of the literature. Bull Tokyo Dent Coll. 2002;43(3):173–80.Google Scholar
19. 19.
    Flechter CDM, BJ, Hogendoorn P, Mertens F, World Health Organization, International Agency for Research on Cancer. Classification of tumours of soft tissue and bone. 5th ed. Lyon: IARC Press. 2013.Google Scholar
20. 20.
    Posnick JC. Fibrous dysplasia of the craniomaxillofacial region: current clinical perspectives. Br J Oral Maxillofac Surg. 1998;36(4):264–73.CrossRefPubMedGoogle Scholar
21. 21.
    Waldron CA. Fibro-osseous lesions of the jaws. J Oral Maxillofac Surg. 1993;51(8):828–35.CrossRefPubMedGoogle Scholar
22. 22.
    Lee JS, FitzGibbon EJ, Chen YR, et al. Clinical guidelines for the management of craniofacial fibrous dysplasia. Orphanet J Rare Dis. 2012;7 Suppl 1:S2.Google Scholar
23. 23.
    Eversole R, Su L, ElMofty S. Benign fibro-osseous lesions of the craniofacial complex. Rev Head Neck Pathol. 2008;2(3):177–202.CrossRefGoogle Scholar
24. 24.
    Tokano H, Sugimoto T, Noguchi Y, et al. Sequential computed tomography images demonstrating characteristic changes in fibrous dysplasia. J Laryngol Otol. 2001;115(9):757–9.Google Scholar
25. 25.
    Brannon RB, Fowler CB. Benign fibro-osseous lesions: a review of current concepts. Adv Anat Pathol. 2001;8(3):126–43.CrossRefPubMedGoogle Scholar
26. 26.
    Fletcher CD, Bridge JA, Hogendoorn P, et al. World Health Organization classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. p. 468.Google Scholar
27. 27.•
    Tabareau-Delalande F, Collin C, Gomez-Brouchet A, et al. Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions. Mod Pathol. 2013;26:911–21. This manuscript represents the first large study indicating that mutational analysis of GNAS gene constitutes a valuable diagnostic tool in fibrous dysplasia in routine practice, in particular allowing to differentiate ossifying fibroma and fibrous dysplasia of the jaws.Google Scholar
28. 28.
    Riminucci M, Liu B, Corsi A, et al. The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: site-specific patterns and recurrent histological hallmarks. J Pathol. 1999;187(2):249–58.Google Scholar
29. 29.
    Gorelov VN, Dumon K, Barteneva NS, et al. Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs alpha gene. J Cancer Res Clin Oncol. 1995;121(4):219–24.Google Scholar
30. 30.
    Lietman SA, Ding C, Levine MA. A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia. J Bone Joint Surg Am. 2005;87(11):2489–94.CrossRefPubMedGoogle Scholar
31. 31.
    Riminucci M, Fisher LW, Majolagbe A, et al. A novel GNAS1 mutation, R201G, in McCune-albright syndrome. J Bone Miner Res. 1999;14(11):1987–9.Google Scholar
32. 32.
    Idowu BD, Al-Adnani M, O’Donnell P, et al. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology. 2007;50(6):691–704.Google Scholar
33. 33.
    Lee SE, Lee EH, Park H, et al. The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases. Hum Pathol. 2012;43(8):1234–42Google Scholar
34. 34.
    Shi RR, Li XF, Zhang R, et al. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod Pathol. 2013;26(8):1023–31.Google Scholar
35. 35.
    Tabareau-Delalande F, Collin C, Larousserie F, et al. Comments on Carter et al.’s “activating GNAS mutations in parosteal osteosarcoma”. Am J Surg Pathol. 2015;39(7):1010–3.Google Scholar
36. 36.
    Salinas-Souza C, De Andrea C, Bihl M, et al. GNAS mutations are not detected in parosteal and low-grade central osteosarcomas. Mod Pathol. 2015;28(10):1336–42.Google Scholar
37. 37.
    Jour G, Oultache A, Sadowska J, et al. GNAS mutations in fibrous dysplasia: a comparative study of standard sequencing and locked nucleic acid PCR sequencing on decalcified and nondecalcified formalin-fixed paraffin-embedded tissues. Appl Immunohistochem Mol Morphol, 2015.Google Scholar
38. 38.
    Guérin M, Thariat J, Ouali M, et al. A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification. Human Pathol. 2016;50:70–8.Google Scholar
39. 39.
    Kuznetsov SA, Cherman N, Riminucci M, et al. Age-dependent demise of GNAS-mutated skeletal stem cells and “normalization” of fibrous dysplasia of bone. J Bone Miner Res. 2008;23(11):1731–40.Google Scholar
40. 40.
    Liang Q, Wei M, Hodge L, et al. Quantitative analysis of activating alpha subunit of the G protein (Gsalpha) mutation by pyrosequencing in fibrous dysplasia and other bone lesions. J Mol Diagn. 2011;13(2):137–42.Google Scholar
41. 41.
    Eversole LR, Leider AS, Nelson K. Ossifying fibroma: a clinicopathologic study of sixty-four cases. Oral Surg Oral Med Oral Pathol. 1985;60(5):505–11.CrossRefPubMedGoogle Scholar
42. 42.•
    El-Mofty SK. Fibro-osseous lesions of the craniofacial skeleton: an update. Head Neck Pathol. 2014;8(4):432–44. This manuscript represents the most recent updated review discussing the radio-clinical, histopathological and molecular features of benign fibro-osseous lesions of the craniofacial complex.CrossRefPubMedPubMedCentralGoogle Scholar
43. 43.
    Commins DJ, Tolley NS, Milford CA. Fibrous dysplasia and ossifying fibroma of the paranasal sinuses. J Laryngol Otol. 1998;112(10):964–8.CrossRefPubMedGoogle Scholar
44. 44.
    Vlachou S, Terzakis G, Doundoulakis G, et al. Ossifying fibroma of the temporal bone. J Laryngol Otol. 2001;115(8):654–6.Google Scholar
45. 45.
    MacDonald-Jankowski DS. Fibro-osseous lesions of the face and jaws. Clin Radiol. 2004;59(1):11–25.CrossRefPubMedGoogle Scholar
46. 46.
    Sciubba JJ, Younai F. Ossifying fibroma of the mandible and maxilla: review of 18 cases. J Oral Pathol Med. 1989;18(6):315–21.CrossRefPubMedGoogle Scholar
47. 47.
    Hamner JE, 3rd, PM Lightbody, Ketcham AS, et al. Cemento-ossifying fibroma of the maxilla. Oral Surg Oral Med Oral Pathol. 1968;26(4):579–87.Google Scholar
48. 48.
    Waldron CA, Giansanti JS. Benign fibro-osseous lesions of the jaws: a clinical-radiologic-histologic review of sixty-five cases. II. Benign fibro-osseous lesions of periodontal ligament origin. Oral Surg Oral Med Oral Pathol. 1973;35(3):340–50.CrossRefPubMedGoogle Scholar
49. 49.
    Zachariades N, Vairaktaris E, Papanicolaou S, et al. Ossifying fibroma of the jaws. Review of the literature and report of 16 cases. Int J Oral Surg. 1984;13(1):1–6.Google Scholar
50. 50.
    Smith AG, Zavaleta A. Osteoma, ossifying fibroma, and fibrous dysplasia of facial and cranial bones. AMA Arch Pathol. 1952;54(6):507–27.PubMedGoogle Scholar
51. 51.
    Sweet RM, Bryarly RC, Kornblut AD, et al. Recurrent cementifying fibroma of the jaws. Laryngoscope. 1981;91(7):1137–44.Google Scholar
52. 52.
    Boysen ME, Olving JH, Vatne K, et al. Fibro-osseous lesions of the cranio-facial bones. J Laryngol Otol. 1979;93(8):793–807.Google Scholar
53. 53.
    Dehner LP. Tumors of the mandible and maxilla in children. I. Clinicopathologic study of 46 histologically benign lesions. Cancer. 1973;31(2):364–84.Google Scholar
54. 54.
    Slootweg PJ. Lesions of the jaws. Histopathology. 2009;54(4):401–18.CrossRefPubMedGoogle Scholar
55. 55.
    Su L, Weathers DR, Waldron CA. Distinguishing features of focal cemento-osseous dysplasia and cemento-ossifying fibromas. II. A clinical and radiologic spectrum of 316 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(5):540–9.CrossRefPubMedGoogle Scholar
56. 56.
    Su L, Weathers DR, Waldron CA. Distinguishing features of focal cemento-osseous dysplasias and cemento-ossifying fibromas: I. A pathologic spectrum of 316 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(3):301–9.CrossRefPubMedGoogle Scholar
57. 57.
    Gollin SM, Storto PD, Malone PS, et al. Cytogenetic abnormalities in an ossifying fibroma from a patient with bilateral retinoblastoma. Genes Chromosomes Cancer. 1992;4(2):146–52.Google Scholar
58. 58.
    Dal Cin P, Sciot R, Fossion E, et al. Chromosome abnormalities in cementifying fibroma. Cancer Genet Cytogenet. 1993;71(2):170–2.Google Scholar
59. 59.
    Sawyer JR, Tryka AF, Bell JM, et al. Nonrandom chromosome breakpoints at Xq26 and 2q33 characterize cemento-ossifying fibromas of the orbit. Cancer. 1995;76(10):1853–9.Google Scholar
60. 60.
    Pimenta FJ, Gontijo Silveira LF, Tavares GC, et al. HRPT2 gene alterations in ossifying fibroma of the jaws. Oral Oncol. 2006;42(7):735–9.Google Scholar
61. 61.
    Zhang TH, Liu HC, Liao GQ, et al. Detection of Notch signaling molecules in cemento-ossifying fibroma of the jaws. J Oral Pathol Med. 2010;39(3):263–8.Google Scholar
62. 62.
    Qin H, Qu C, Yamaza T, et al. Ossifying fibroma tumor stem cells are maintained by epigenetic regulation of a TSP1/TGF-beta/SMAD3 autocrine loop. Cell Stem Cell. 2013;13(5):577–89.Google Scholar
63. 63.
    Patel MM, Wilkey JF, Abdelsayed R, et al. Analysis of GNAS mutations in cemento-ossifying fibromas and cemento-osseous dysplasias of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(5):739–43.Google Scholar
64. 64.•
    Shi RR, Li XF, Zhang R, et al. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod Pathol. 2013;26:1023–31. This manuscript represents a large recent study confirming that mutational analysis of GNAS gene is a reliable adjunct to differentiate ossifying fibroma and fibrous dysplasia of the jaws.Google Scholar
65. 65.•
    Dujardin F, Binh MB, Bouvier C, et al. MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone. Mod Pathol. 2011;24(5):624–37. This manuscript represents the first immunohistochemical and molecular study showing that MDM2 espression/amplification is a sensitive marker for the diagnosis of low-grade osteosarcomas.Google Scholar
66. 66.
    El-Mofty S. Psammomatoid and trabecular juvenile ossifying fibroma of the craniofacial skeleton: two distinct clinicopathologic entities. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(3):296–304.CrossRefPubMedGoogle Scholar
67. 67.
    Slootweg PJ, Muller H. Differential diagnosis of fibro-osseous jaw lesions. A histological investigation on 30 cases. J Craniomaxillofac Surg. 1990;18(5):210–4.CrossRefPubMedGoogle Scholar
68. 68.
    Barnes L, Eveson JW, Reichart P, et al. World Health Organization Classification of Tumours. Pathology and genetics of head and neck tumours. 2005, Lyon: IARC Press. 430.Google Scholar
69. 69.
    Sarode, SC, Sarode GS, Waknis P, et al. Juvenile psammomatoid ossifying fibroma: a review. Oral Oncol. 2011;47(12):1110–6.Google Scholar
70. 70.
    Phattarataratip E, Pholjaroen C, Tiranon P. A clinicopathologic analysis of 207 cases of benign fibro-osseous lesions of the jaws. Int J Surg Pathol. 2014;22(4):326–33.CrossRefPubMedGoogle Scholar
71. 71.
    Johnson LC, Yousefi M, Vinh TN, et al. Juvenile active ossifying fibroma. Its nature, dynamics and origin. Acta Otolaryngol Suppl. 1991;488:1–40.Google Scholar
72. 72.
    Han J, Hu L, Zhang C, et al. Juvenile ossifying fibroma of the jaw: a retrospective study of 15 cases. Int J Oral Maxillofac Surg, 2016;45(3):368–76.Google Scholar
73. 73.
    Makek MS. So called “fibro-osseous lesions” of tumorous origin. Biology confronts terminology. J Craniomaxillofac Surg. 1987;15(3):154–67.CrossRefPubMedGoogle Scholar
74. 74.
    Makek M. Clinical pathology and differential diagnosis of fibro-osseous lesions of the maxillofacial area--new aspects. Dtsch Z Mund Kiefer Gesichtschir. 1986;10(3):212–7.PubMedGoogle Scholar
75. 75.•
    Tabareau-Delalande F, Collin C, Gomez-Brouchet A, et al. Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions. Mod Pathol. 2015;28(1):48–56. This manuscript reports the first recurrent molecular abnormality, with a potential prognostic significance, to be observed in juvenile ossifying fibroma.Google Scholar
76. 76.
    Weaver J, Downs-Kelly E, Goldblum JR, et al. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol. 2008;21(8):943–9.Google Scholar
77. 77.
    Sirvent N, Coindre JM, Maire G, et al. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol. 2007;31(10):1476–89.Google Scholar
78. 78.
    Thariat, J, Julieron M, Brouchet A, et al. Osteosarcomas of the mandible: are they different from other tumor sites? Crit Rev Oncol Hematol. 2012;82(3):280–95.Google Scholar
79. 79.•
    Thariat J, Schouman T, Brouchet A, et al. Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network. GETTEC/REFCOR and SFCE Ann Oncol. 2013;24(3):824–31. This manuscript represents the largest homogeneous series on multidisciplinary management of osteosarcoma of the mandible.Google Scholar
80. 80.
    Liu XW, Zi Y, Xiang LB, et al, Periosteal osteosarcoma: a review of clinical evidence. Int J Clin Exp Med. 2015;8(1):37–44.Google Scholar
81. 81.
    Yoshida A, Ushiku T, Motoi T, et al. Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics. Mod Pathol. 2010;23(9):1279–88.Google Scholar
82. 82.
    Yoshida A, Ushiku T, Motoi T, et al. MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype. Am J Surg Pathol. 2012;36(3):423–31.Google Scholar