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The application of immunohistochemistry in the diagnosis of bone tumors and tumor-like lesions

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Abstract

Immunohistochemistry (IHC) plays an important role in the diagnosis of some bone tumors, especially in the differential diagnosis of primary from metastatic non-osseous tumors and in the categorization of small-round-blue-cell tumors. This article reviews immunomarkers used in bone tumors and their diagnostic significance.

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References

  1. Coons AH. Labeled antigens and antibodies. Annu Rev Microbiol 1954;8:333–52

    Article  PubMed  CAS  Google Scholar 

  2. Nakane PK, Pierce GB Jr. Enzyme-labeled antibodies for the light and electron microscopic localization of tissue antigens. J Cell Biol 1967;33 2:307–18

    Article  PubMed  CAS  Google Scholar 

  3. Eckert F, de Viragh PA, Schmid U. Coexpression of cytokeratin and vimentin intermediate filaments in benign and malignant sweat gland tumors. J Cutan Pathol 1994;21 2:140–50

    Article  PubMed  CAS  Google Scholar 

  4. Azumi N, Battifora H. The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors. Am J Clin Pathol 1987;88 3:286–96

    PubMed  CAS  Google Scholar 

  5. Miettinen M. Keratin subsets in spindle-cell sarcomas: keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins. Am J Pathol 1991;138:505–13

    PubMed  CAS  Google Scholar 

  6. Kahn LB. Adamantinoma, osteofibrous dysplasia and differentiated adamantinoma. Skelet Radiol 2003;32 5:245–58

    Article  Google Scholar 

  7. O’Hara BJ, Paetau A, Miettinen M. Keratin subsets and monoclonal antibody HBME-1 in chordoma: immunohistochemical differential diagnosis between tumors simulating chordoma. Human Pathol 1998;29:119–26

    Article  CAS  Google Scholar 

  8. Gray MH, Rosenberg AE, Dickersin GR, Bhan AK. Cytokeratin expression in epithelioid vascular neoplasms. Human Pathol 1990;21 2:212–7

    Article  CAS  Google Scholar 

  9. O’Connell JX, Kattapuram SV, Mankin HJ, Bhan AK, Rosenberg AE. Epithelioid hemangioma of bone. A tumor often mistaken for low-grade angiosarcoma or malignant hemangioendothelioma. Am J Surg Pathol 1993;17 6:610–7

    Article  PubMed  CAS  Google Scholar 

  10. Aigner T, Frischholz S, Dertinger S. Type X collagen expression and hypertrophic differentiation in chondrogenic neoplasias. Histochem Cell Biol 1997;107:435–40

    Article  PubMed  CAS  Google Scholar 

  11. Granter SR, Renshaw AA, Fletcher CD. CD99 reactivity in mesenchymal chondrosarcoma. Human Pathol 1996;27:1273–6

    Article  PubMed  CAS  Google Scholar 

  12. Folpe AL, Schmidt RA, Chapman D, Gown AM. Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors. Am J Surg Pathol 1998;22 6:673–82

    Article  PubMed  CAS  Google Scholar 

  13. Theaker JM, Gatter KC, Esiri MM Fleming KA. Epithelial membrane antigen and cytokeratin expression by meningiomas: an immunohistological study. J Clin Pathol 1986;39 4:435–9

    Article  PubMed  CAS  Google Scholar 

  14. Swanson C, Perentes E, Phillips L. Epithelial membrane antigen reactivity in mesenchymal neoplasms: an immunohistochemical study of 306 soft tissue sarcomas. Surg Pathol 1992;2:313–22

    Google Scholar 

  15. Park HR, Park YK, Jang KT, Unni KK. Expression of collagen type II, S100B, S100A2 and osteocalcin in chondroblastoma and chondromyxoid fibroma. Oncol Rep 2002;9:1087–91

    PubMed  CAS  Google Scholar 

  16. Nakajima T, Kameya T, Watanabe S. S-100 protein distribution in normal and neoplastic tissues. In: DeLellis R, editor. Advances in immunohistochemistry. New York: Mason; 1984. pp. 141–58

    Google Scholar 

  17. Bleiweiss IJ, Klein MJ. Chondromyxoid fibroma: report of six cases with immunohistochemical studies. Mod Pathol 1990;3:664–6

    PubMed  CAS  Google Scholar 

  18. Monda L, Wick MR. S-100 protein immunostaining in the differential diagnosis of chondroblastoma. Human Pathol 1985;16:287–293

    Article  CAS  Google Scholar 

  19. Gebhard S, Coindre JM, Michels JJ, Terrier P, Bertrand G, Trassard M, Taylor S, Chateau MC, Marques B, Picot V, Guillou L. Pleomorphic liposarcoma. Clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2002;26 5:601–16

    Article  PubMed  Google Scholar 

  20. Folpe AL, Weiss SW. Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants. Am J Surg Pathol 2003;27 4:421–31

    Article  PubMed  Google Scholar 

  21. Rosenberg AE, Nielsen GP, Keel SB, Renard LG, Fitzek MM, Munzenrider JE, Liebsch NJ. Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. Am J Surg Pathol 1999;23 11:1370–8

    Article  PubMed  CAS  Google Scholar 

  22. Pinkus GS, Lones MA, Matsumura F, Yamashiro S, Said JW, Pinkus JL. Langerhans cell histiocytosis immunohistochemical expression of fascin, a dendritic cell marker. Am J Clin Pathol 2002;118 3:335–43

    Article  PubMed  CAS  Google Scholar 

  23. Arber DA, Weiss LM. CD57: a review. Appl Immunohistochem 1995;3:137–52

    CAS  Google Scholar 

  24. Gould VE, Lee I, Wiedenmann B. Synaptophysin: a novel marker for neurons, certain neuroendocrine cells, and their neoplasms. Human Pathol 1986;17:979–83

    Article  CAS  Google Scholar 

  25. De Young BR, Frierson HF Jr, Ly MN, Smith D, Swanson PE. CD31 immunoreactivity in carcinomas and mesotheliomas. Am J Clin Pathol 1998;110:374–7

    PubMed  Google Scholar 

  26. Miettinen M, Lindenmayer AE, Chaubal A. Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y-antigens—evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. Mod Pathol 1994;7 1:82–90

    PubMed  CAS  Google Scholar 

  27. Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Human Pathol 1999;30 11:1336–43

    Article  CAS  Google Scholar 

  28. Lessard JL. Two monoclonal antibodies to actin: one muscle selective and one generally reactive. Cell Motil Cytoskelet 1988;10 3:349–62

    Article  CAS  Google Scholar 

  29. Sebire NJ, Malone M. Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas. J Clin Pathol 2003;56 6:412–6

    Article  PubMed  CAS  Google Scholar 

  30. Llombart-Bosch A, Navarro S. Immunohistochemical detection of EWS and FLI-1 proteins in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression. Appl Immunohistochem Mol Morphol 2001;9 3:255–60

    Article  PubMed  CAS  Google Scholar 

  31. Amann G, Zoubek A, Salzer-Kuntschik M, Windhager R, Kovar H. Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family. Human Pathol 1999;30 9:1058–64

    Article  CAS  Google Scholar 

  32. Garin-Chesa P, Fellinger EJ, Huvos AG, Beresford HR, Melamed MR, Triche TJ, Rettig WJ. Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence. Am J Pathol 1991;139 2:275–86

    PubMed  CAS  Google Scholar 

  33. Miettinen M, Cupo W. Neural cell adhesion molecule distribution in soft tissue tumors. Human Pathol 1993;24 1:62–6

    Article  CAS  Google Scholar 

  34. Folpe AL, Hill CE, Parham DM, O’Shea PA, Weiss SW. Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor. Am J Surg Pathol 2000;24 12:1657–62

    Article  PubMed  CAS  Google Scholar 

  35. Bacchi CE, Bonetti F, Pea M. HMB-45, a review. Appl Immunohistochem 1996;4:73–80

    CAS  Google Scholar 

  36. Gao ZQ, Bhuiya T, Anderson A. Perivascular epithelioid cell tumor (PEComa) of the uterus associated with malignant neoplasm of the female genital tract: a case report and literature review. J Obstet Gynaecol 2004;5:600–4

    Article  Google Scholar 

  37. Fanburg-Smith JC, Bratthauer GL, Miettinen M. Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: a study of 28 cases. Human Pathol 1999;30 1:32–8

    Article  CAS  Google Scholar 

  38. Fanburg JC, Rosenberg AE, Weaver DL. Osteocalcin and osteonectin immunoreactivity in the diagnosis of osteosarcoma. Am J Clin Pathol 1997;108 4:464–73

    PubMed  CAS  Google Scholar 

  39. Serra M, Morini MC, Scotlandi K, Fisher LW, Zini N, Colombo MP, Campanacci M, Maraldi NM, Olivari S, Baldini N. Evaluation of osteonectin as a diagnostic marker of osteogenic bone tumors. Human Pathol 1992;23 12:1326–31

    Article  CAS  Google Scholar 

  40. Hall PA, Richards MA, Gregory WM, d'Ardenne AJ, Lister TA, Stansfeld AG. The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma. J Pathol 1988;154 3:223–35

    Article  PubMed  CAS  Google Scholar 

  41. Ueda T, Aozasa K, Tsujimoto M, Ohsawa M, Uchida A, Aoki Y, Ono K, Matsumoto K. Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer 1989;63 8:1607–11

    Article  PubMed  CAS  Google Scholar 

  42. Okamoto S, Hisaoka M, Ishida T, Imamura T, Kanda H, Shimajiri S, Hashimoto H. Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 18 cases. Human Pathol 2001;32 10:1116–24

    Article  CAS  Google Scholar 

  43. Edel G, Ueda Y, Nakanishi J, Brinker KH, Roessner A, Blasius S, Vestring T, Muller-Miny H, Erlemann R, Wuisman P. Chondroblastoma of bone. A clinical, radiological, light and immunohistochemical study. Virchows Arch 1992;421 4:355–66

    Article  CAS  Google Scholar 

  44. Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: an immunohistochemical comparative study. Pathol Int 1998;48 5:355–61

    Article  PubMed  CAS  Google Scholar 

  45. Nielsen GP, Keel SB, Dickersin GR, Selig MK, Bhan AK, Rosenberg AE. Chondromyxoid fibroma: a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation. Mod Pathol 1999;12 5:514–7

    PubMed  CAS  Google Scholar 

  46. Almeida J, Orfao A, Mateo G, Ocqueteau M, Garcia-Sanz R, Moro MJ, Hernandez J, Ortega F, Borrego D, Barez A, Mejido M, San Miguel JF. Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance. Pathol Biol (Paris) 1999;47 2:119–27

    CAS  Google Scholar 

  47. Tworek JA, Singleton TP, Schnitzer B, Hsi ED, Ross CW. Flow cytometric and immunohistochemical analysis of small lymphocytic lymphoma, mantle cell lymphoma, and plasmacytoid small lymphocytic lymphoma. Am J Clin Pathol 1998;110 5:582–9

    PubMed  CAS  Google Scholar 

  48. Heyning FH, Hogendoorn PC, Kramer MH, Hermans J, Kluin-Nelemans JC, Noordijk EM, Kluin PM. Primary non-Hodgkin's lymphoma of bone: a clinicopathological investigation of 60 cases. Leukemia 1999;13 12:2094–8

    Article  PubMed  CAS  Google Scholar 

  49. Lopez P, Estes ML. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy: analysis of an extranodal case. Human Pathol 1989;20:711–5

    Article  Google Scholar 

  50. Myers JL, Bernreuter W, Dunham W. Melanotic schwannoma. Clinicopathologic, immunohistochemical, and ultrastructural features of a rare primary bone tumor. Am J Clin Pathol 1990;93 3:424–9

    PubMed  CAS  Google Scholar 

  51. Karabela-Bouropoulou V, Markaki S, Prevedorou D, Vidali N. A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms. Pathol Res Pract 1989;184 2:184–7

    PubMed  CAS  Google Scholar 

  52. Panico L, Passeretti U, De Rosa N. Giant cell reparative granuloma of the distal skeletal bones: a report of five cases with immunohistochemical findings. Virchows Arch 1994;425:315–20

    Article  PubMed  CAS  Google Scholar 

  53. Maruno M, Yoshimine T, Kubo T. A case of giant cell reparative granuloma of the petrous bone: demonstration of the proliferative component. Surg Neurol 1997;48:64–8

    Article  PubMed  CAS  Google Scholar 

  54. Juliao SF, Rand N, Schwartz HS. Galectin-3: a biologic marker and diagnostic aid for chordoma. Clin Orthop 2002;397:70–5

    Article  PubMed  Google Scholar 

  55. Hall PA, O’Doherty CJ, Levison DA. Langerhan's cell histiocytosis: an unusual case illustrating the value of immunohistochemistry in diagnosis. Histopathology 1988;12 4:458

    Article  PubMed  CAS  Google Scholar 

  56. Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan JK, Favera RD, Delsol G, De Wolf-Peeters C, Falini B, Gascoyne RD, Gaulard P, Gatter KC, Isaacson PG, Jaffe ES, Kluin P, Knowles DM, Mason DY, Mori S, Muller-Hermelink HK, Piris MA, Ralfkiaer E, Stein H, Su IJ, Warnke RA, Weiss LM. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002;41:1–29

    Article  PubMed  CAS  Google Scholar 

  57. Dillon KM, Hill CM, Cameron CH, Attanoos RL, McCluggage WG. Mediastinal mixed dendritic cell sarcoma with hybrid features. J Clin Pathol 2002;55:791–4

    Article  PubMed  CAS  Google Scholar 

  58. World Health Organization. Classification of tumors. Tumors of the hematopoietic and lymphoid tissues. IARC Press; 2001

  59. Hanson CA, Jaszcz W, Kersey JH, Astorga MG, Peterson BA, Gajl-Peczalska KJ, Frizzera G. True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis. Br J Haematol 1989;73 2:187–98

    PubMed  CAS  Google Scholar 

  60. Egan AJ, Boardman LA, Tazelaar HD, Swensen SJ, Jett JR, Yousem SA, Myers JL. Erdheim–Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol 1999;23 1:17–26

    Article  PubMed  CAS  Google Scholar 

  61. World Health Organization. Classification of tumors. Tumors of the soft tissue and bone. IARC Press; 2002

  62. Eisen RN, Buckley PJ, Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease). Semin Diagn Pathol 1990;7 1:74–82

    PubMed  CAS  Google Scholar 

  63. Tzankov A, Zimpfer A, Pehrs AC, Lugli A, Went P, Maurer R, Pileri S, Dirnhofer S. Expression of B-cell markers in classical Hodgkin lymphoma: a tissue microarray analysis of 330 cases. Mod Pathol 2003;16 11:1141–7

    Article  PubMed  Google Scholar 

  64. O’Neill MC, Song L. Neural network analysis of lymphoma microarray data: prognosis and diagnosis near-perfect. BMC Bioinformatics 2003;4 1:13

    Article  PubMed  Google Scholar 

  65. Li S, Ross DT, Kadin ME, Brown PO, Wasik MA. Comparative genome-scale analysis of gene expression profiles in T cell lymphoma cells during malignant progression using a complementary DNA microarray. Am J Pathol 2001;158 4:1231–7

    PubMed  CAS  Google Scholar 

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Gao, Z., Kahn, L.B. The application of immunohistochemistry in the diagnosis of bone tumors and tumor-like lesions. Skeletal Radiol 34, 755–770 (2005). https://doi.org/10.1007/s00256-005-0001-4

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