Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Immunohistological evidences of cortical and medullary differentiation in thymoma

Summary

The phenotypical characteristics of human epithelial and lymphoid cells have been studied with immunohistochemical methods on frozen sections of 12 thymomas. On the basis of the cytohistological characteristics of thymoma epithelial cells (EC) the thymomas were divided in cortical, medullary and mixed types, according to recently developed light microscopical criteria. When tested with a series of monoclonal antibodies, thymoma EC were all stained by the antibody Ki-M3 (as in the thymus), but reacted with anti-HLA-DR, anti-HLA-A,B,C and with a new monoclonal antibody to cortical EC,21A6, to a lesser extent and with weaker, variable intensity in comparison with the normal thymus. Cortical type thymomas were most reactive and the medullary type almost negative. Thymomas, like normal thymus showed different immunoreactivity patterns with antibodies to prekeratins of different specificities. Cortical type thymomas and areas in mixed thymoma showed an EC staining with the antibody to non-squamous type keratin (35βH11) whereas medullary type thymomas and areas showed staining with antibodies to squamous-type keratin (34βE12-IV/82) in addition. Lymphoidcellswithcortical(OKT6+,Leu 1 weakly+,Leu2a+,Leu3a+) or mature medullary (OKT6-, Leu 1 strongly+, Leu 2a or Leu 3a+) phenotype were found to colonize tumours with diferent EC types. These immunohistochemical findings largely confirm our earlier cytological distinction of thymoma EC. In addition important differences have been observed in neoplastic cortical EC concerning the HLA-DR and 21A6 immunoreactivity that may be intimately related to the neoplastic process and paraneoplastic immune phenomena.

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

References

  1. Castleman B (1955) Tumours of the thymus gland. In:Atlas of Tumor Pathology, Fascicle 19. Armed Forces Institute of Pathology, Washington

  2. Chan WC, Zaatari GS, Tabei S, Bibb M, Brynes RK (1984) Thymoma: an immunohistochemical study. Am J Clin Pathol 82:160–166

  3. Chilosi M, Menestrina F, Iannucci AM, Fiore-Donati L, Pizzolo G, Janossy G (1984) Immunohistochemical analysis of thymoma. Evidence for medullary origin of epithelial cells. Am J Surg Pathol 8:309–318

  4. McFarland EJ, Scearce RM, Haynes BF (1984) The human thymic microenvironemnt:cortical thymic epithelium is an antigenically distinct region of the thymic microenvironment. J Immunol 133:1241–1249

  5. Gaudecker B von (1985) The development of human thymus microenvironment. In:Müller-Hermelink HK (ed) Histophysiology and pathology of the human thymus. Current Topics in Pathology, vol. 75, Springer Verlag, Berlin Heidelberg New York, in press

  6. Graham RC, Karnovsky MJ (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney. Ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14:219–302

  7. Gray GF, Gutowski WT III (1979) Thymoma. A clinicopathologic study of 54 cases. Am J Surg Pathol 3:235–249

  8. Haynes BF (1984) The human thymic microenvironment. In:Dixon FJ (ed) Advances in Immunology, vol 36. Academic Press Inc., Orlando San Diego New York, pp 87–142

  9. Haynes BF, Robert-Guroff M, Metzgar RS, Franchini G, Kalyanaraman VS, Palker TJ, Gallo RC (1983) Monoclonal antibody against human T-cell leukemia virus p19 definies a human thymic epithelial antigen acquired during ontogeny. J Exp Med 157:907–920

  10. Haynes BF, Scearce RM, Lobach DF, Hensley LL (1984) Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment. J Exp Med 159:1149–1168

  11. Hofmann W, Möller P, Momburg F, Moldenhauer G, Otto HF (1984) Struktur des normalen Thymus, der lymphofollikulären Thymushyperplasie und der Thymome, dargestellt mit Lectinen, S-100-Protein- und Keratin Antiseren, und monoklonalen (epitheliotropen) Antikörpern. Verh Dtsch Ges Path 68:504

  12. Hofmann W, Möller P, Manke H-G, Otto HF (1985) Thymoma. A clinicopathologic study of 98 cases with special reference to three unusual cases. Path Res Pract 179:337–353

  13. Janossy G, Bofill M, Trejdosiewicz LK, Poulter LW, Chilosi M, Newson-Davis J (1985) Cellular differentiation of lymphoid subpopulations and their microenvironment in the human thymus. In:Müller-Hermelink HK (ed) Histophysiology and pathology of the human Thymus. Current Topics in Pathology, vol. 75, Springer Verlag, Berlin Heidelberg New York, in press

  14. Kuroda Y, Oda K-I, Neshige R, Shibasaki H (1984) Exacerbation of myasthenia gravis after removal of a thymoma having a membrane phenotype of suppressor T cells. Ann Neurol 15:400–402

  15. Lattes R (1962) Thymoma and other tumors of the thymus. An analysis of 107 cases. Cancer 15:1224–1260

  16. Lauriola L, Maggiano N, Marino M, Carbone A, Piantelli M, Musiani P (1981) Human thymoma: immunologic characteristics of the lymphocytic component. Cancer 48:1992–1995

  17. Lauriola L, Musiani P, Ranelletti FO, Maggiano N, Piantelli M (1983) Human thymoma lymphocyte mytogenesis: glucocorticoid inhibitory capacity as a function of the size of the more mature T cells subset. Clin Exp Immunol 52:477–484

  18. Levine GD, Bensch KG (1972) Epithelial nature of spindle-cell thymoma. An ultrastructural study. Cancer 30:500–511

  19. Marino M, Müller-Hermelink HK (1985) Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. Virchows Arch [Pathol Anat] 407:119–149

  20. Mokhtar N, Hsu S-M, Rajnikant P, Haynes BF, Jaffe ES (1984) Thymoma: lymphoid and epithelial components mirror the phenotype of normal thymus. Hum Pathol 15:378–384

  21. Müller-Hermelink HK, Marino M (1984) Zytologische Befunde und Malignitatskriterien menschlicher Thymome. Verh Dtsch Ges Path 68:454

  22. Müller-Hermelink HK, Steinmann GG (1984) Age-related alternations of intrathymic microenvironments. In: De Week AL (ed) Lymphoid cell functions in aging. Topics in aging research in Europe, vol 3. Rijswijk Eurage, pp 75–82

  23. Müller-Hermelink HK, Marino M, Palestro G (1985) Pathology of thymic epithelial tumors. In:Müller-Hermelink HK (ed) Histophysiology and pathology of the human thymus. Current Topics in Pathology, vol. 75, Springer Verlag, Berlin Heidelberg New York, in press

  24. Musiani P, Lauriola L, Maggiano N, Tonali P, Piantelli M (1982) Functional properties of human thymoma lymphocytes: role of subcellular factors in blastic activation. J Natl Cancer Inst 69:827–831

  25. Reddick RL, Jennette JC (1983) Immunologic and ultrastructural characterization of the small cell population in malignant thymoma. Hum Pathol 14:377–380

  26. Ritter MA, Sauvage CA, Cotmore SF (1981) The human thymus microenvironment: in vivo identification of thymic nurse cells and other antigenically distinct subpopulations of epithelial cells. Immunology 44:439–446

  27. Rosai J, Levine GD (1976) Tumors of the thymus. In:Atlas of Tumor Pathology. 2nd Series, Fascicle 13. Armes Forces Institute of Pathology, Washington

  28. Savino W, Berrih S, Dardenne M (1984) Thymic epithelial antigen, acquired during ontogeny and definied by the anti-p19 monoclonal antibody, is lost in thymomas. Lab Invest 51:292–296

  29. Sternberger LA, Hardy PH jr. Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish perioxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333

  30. Verley JM, Hollmann KH (1985) Thymoma. A comparative Study of clinical stages, histologic features and survival in 200 cases. Cancer 55:1074–1086

  31. Wekerle H, Müller-Hermelink HK (1985) The thymus in myasthenia gravis. In: Müller-Hermelink HK (ed) Histophysiology and pathology of the human thymus. Current Topics in Pathology, vol. 75, Springer Verlag, Berlin Heidelberg New York, in press

  32. Wijngaert FP van de, Kendall MD, Schuurman H-J, Rademakers LHPM, Kater L (1984) Heterogeneity of epithelial cells in the human thymus. An ultrastructural study. Cell Tissue Res 237:227–237

  33. Woda BA, Bain K, Salm T van der (1984) The phenotype of lymphocytes in a thymoma as studied with monoclonal antibodies. Clin Immunol Immunopathol 30:197–201

Download references

Author information

Correspondence to Hans Konrad Müller-Hermelink.

Additional information

This work has been supported by the Deutsche Forschungsgemeinschaft, SFB 111, project CN5

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Müller-Hermelink, H.K., Marino, M., Palestro, G. et al. Immunohistological evidences of cortical and medullary differentiation in thymoma. Vichows Archiv A Pathol Anat 408, 143–161 (1985). https://doi.org/10.1007/BF00707978

Download citation

Key words

  • Thymoma
  • cortical/medullary differentiation
  • Immunohistology