Skip to main content
SpringerLink
Log in

Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis

  • Published:
Virchows Archiv B

Summary

Non-neoplastic thymuses from 20 patients with myasthenia gravis (MG) have been studied by routine stains on paraffin sections and by immunohistological methods on frozen sections using a panel of monoclonal antibodies against thymic epithelial cells, macrophages/ reticulum cells, lymphoid cells and myoid cells. Three types of thymic histology in MG were distinguished: (1) thymitis with lymphoid follicular hyperplasia (11 cases), (2) thymitis with diffuse B-cell infiltration (5 cases) and (3) thymic atrophy (4 cases). Thymitis was more common in younger females and thymic atrophy in older patients.

Both types of thymitis were associated with conspicious structural disturbance of the thymic perivascular space (PVS) and medulla, characterized by a distinct enlargement of the PVS and disruption of the epithelium and reticulin fibre network at the medullary boundary, leading to fusion of the two compartments. The PVS and medulla contained a striking B-cell infiltration. Large well-developed germinal centers (GCs), showing the same cellular organization as in the peripheral lymphatic system, occurred in thymitis with lymphoid follicular hyperplasia, whereas thymitis with diffuse B-cell infiltration merely exhibited a few tiny lymphoid follicles, which could be demonstrated only by immunostaining of dendritic reticulum cells. In thymic atrophy a diffuse B-cell infiltration of the PVS and the medulla was also observed, but only minor alterations of the epithelial framework were seen.

There was an increased number of interdigitating reticulum cells with variable expression of the T-6 antigen in all the thymuses examined, indicating an immune stimulation of the intrathymic T-cells. Myoid cells, the supposed target of the intrathymic immune reaction in MG, were found to be less frequent in thymic atrophy than in thymitis. This variable number of myoid cells may explain the different grades of immune stimulation and different types of histology seen in the thymus in MG.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alpert LI, Papatestas A, Kark A, Osserman RS, Osserman K (1971) A histologic reappraisal of the thymus in myasthenia gravis. Arch Pathol 91:55–61

    PubMed  CAS  Google Scholar 

  • Bofill M, Janossy G, Willcox N, Chilosi M, Trejdosiewicz K, Newsom-Davis J (1985) Microenvironments in the normal thymus and the thymus in myasthenia gravis. Am J Pathol 119:462–473

    PubMed  CAS  Google Scholar 

  • Castleman B, Norris EH (1949) The pathology of the thymus in myasthenia gravis. Medicine 28:27–58

    PubMed  CAS  Google Scholar 

  • Compston AS, Vincent A, Newsom-Davis J, Batchelor JR (1980) Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 103:579–601

    Article  PubMed  CAS  Google Scholar 

  • Drenckhahn D, von Gaudecker B, Müller-Hermelink HK, Unsicker K, Gröschel-Stewart U (1979) Myosin and actin containing cells in the human postnatal thymus. Ultrastructural and immunohistochemical findings in normal thymus and in myasthenia gravis. Virchows Arch [Cell Pathol] 32:33–45

    Article  CAS  Google Scholar 

  • Feller AC, Parwaresch MR, Wacker H-H, Radzun JH, Lennert K (1983) Combined immunohistochemical staining for surface IgD and T lymphocyte subsets with monoclonal antibodies in human tonsils. Histochem J 15:557–562

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Goldstein G (1966II) Thymitis and myasthenia gravis. Lancet 1164–1167

  • Gown AM Vogel AM (1982) Monoclonal antibodies to intermediate filament proteins of human cells: Unique and cross-reacting antibodies. J Cell Biol 95:414–424

    Article  PubMed  CAS  Google Scholar 

  • Hsu SM, Raine H, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. A comparision between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:291–302

    Google Scholar 

  • Janossy G, Tidman N, Papageorgiou ES, Kung PC, Goldstein G (1981) Distribution of T lymphocyte subsets in the human bone marrow and thymus — an analysis with monoclonal antibodies. J Immunol 126:1608–1613

    PubMed  CAS  Google Scholar 

  • Janossy G, Bofill M, Trejdosiewicz LK, Willcox HNA, Chilosi M (1986) Cellular differentiation of lymphoid subpopulations and their microenvironments in the human thymus. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Current topics in pathology, vol. 75. Springer, Berlin Heidelberg New York Tokyo, pp 89–125

    Google Scholar 

  • Kao I, Drachman DB (1977) Thymus muscle cells bear acetylcholine receptors: possible relation to myasthenia gravis. Science 195:74–75

    Article  PubMed  CAS  Google Scholar 

  • Kaplow LS (1968) Leucocyte alkaline phosphatase cytochemistry: applications and methods. Ann NY Acad Sci (USA) 155:911–947

    Article  CAS  Google Scholar 

  • Kornstein MJ, Brooks JJ, Anderson AO, Levinson AI, Lisak RP, Zweiman B (1984) The immunohistology of the thymus in myasthenia gravis. Am J Pathol 117:184–194

    PubMed  CAS  Google Scholar 

  • Lennert K, Stein H (1982) The germinal center: morphology, histochemistry, and immunohistology. In: Goos M, Christophers E (eds) Lymphoproliferative diseases of the skin. Springer, Berlin Heidelberg New York Tokyo, pp 3–15

    Google Scholar 

  • Levine GD, Rosai J (1978) Thymic hyperplasia and neoplasia: A review of current concepts. Hum Pathol 9:495–515

    PubMed  CAS  Google Scholar 

  • Lojda Z, Gossrau R, Schiebler TH (1976) Enzymhistochemische Methoden. Springer, Berlin Heidelberg New York

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Melms A, Endler B, Kirchner Th, Schalke BCG, Müller-Hermelink HK, Wekerle H (1986) The thymus in myasthenia gravis: functional and morphological studies. Ann NY Acad Sci (USA) (in press)

  • Müller-Hermelink HK, Steinmann GG (1984) Age-related alterations of intrathymic microenvironment. In: De Weck AL (ed) Lymphoid functions in aging. Topics in aging research in Europe, vol 3, Rijswijk, Eurage, pp 75–82

    Google Scholar 

  • Müller-Hermelink HK, Marino M, Palestro G, Schumacher U, Kirchner Th (1985) Immunohistological evidences of cortical and medullary differentiation in thymoma. Virchows Arch [Pathol Anat] 408:143–161

    Article  Google Scholar 

  • Müller-Hermelink HK, Marino M, Palestro G (1986) Pathology of thymic epithelial tumors. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Current topics in pathology, vol. 75. Springer, Berlin Heidelberg New York Tokyo, pp 207–268

    Google Scholar 

  • Müller-Hermelink HK, Steinmann GG, Stein H (1982) Structural and functional alterations of the aging human thymus. Adv Exp Med Biol 149:303–312

    PubMed  Google Scholar 

  • Ormanns W, Pfeifer U (1981) A simple method for incubation of tissue sections in immunohistochemistry. Histochemistry 72:315–319

    Article  PubMed  CAS  Google Scholar 

  • Osserman KE, Genkins G (1971) Studies in myasthenia gravis: Review of a twenty-year experience in over 1200 patients. Mt Sinai J Med 38:497–537

    PubMed  CAS  Google Scholar 

  • Otto HF (1984) Pathologie des Thymus. Springer, Berlin Heidelberg New York Tokyo

    Google Scholar 

  • Palestro G, Tridente G, Micca FB, Novero D, Valente G, Godio L (1983) Immunohistochemical and enzyme histochemical contributions to the problem concerning the role of the thymus in the pathogenesis of myasthenia gravis. Virchows Arch [Cell Pathol] 44:172–186

    Article  Google Scholar 

  • Parwaresch MR, Radzun HJ, Hansmann M-L, Peters K-P (1983) Monoclonal antibody Ki-M4 specifically recognizes human dendritic reticulum cells (follicular dendritic cells) and their possible precursor in blood. Blood 62:585–590

    PubMed  CAS  Google Scholar 

  • Pizzighella S, Riviera AP, Tridente G (1983) Thymic involvement in myasthenia gravis. Study by immunofluorescent and immunoperoxidase staining. J Neuroimmunol 4:117–127

    Article  PubMed  CAS  Google Scholar 

  • Ponder BA, Wilkinson MM (1981) Inhibition of endogenous tissue alkaline phosphatase with the use of alkaline phosphatase conjugates in immunohistochemistry. J Histochem Cytochem 29:981–984

    PubMed  CAS  Google Scholar 

  • Radzun HJ, Parwaresch MR (1983) Differential immunohistochemical resolution of the human mononuclear phagocytic system. Cell Immunol 82:174

    Article  PubMed  CAS  Google Scholar 

  • Scadding GK, Vicent A, Newsom-Davis J, Henry K (1981) Acetylcholine receptor antibody synthesis by thymic lymphocytes: correlation with thymic histology. Neurology 31:935–943

    PubMed  CAS  Google Scholar 

  • Simpson JA (1958) An evaluation of thymectomy in myasthenia gravis. Brain 81:112–144

    Article  PubMed  CAS  Google Scholar 

  • Sloan HE (1943) The thymus in myasthenia gravis with observations on the normal anatomy and histology of the thymus. Surgery 13:154–174

    Google Scholar 

  • Söderström N, Axelsson J-A, Hagelqvist E (1970) Postcapillary venules of the lymph node type in the thymus in myasthenia gravis. Lab Invest 23:451–458

    PubMed  Google Scholar 

  • Stein H, Gerdes J, Mason DY (1982a) The normal and malignant germinal centre. Clin Haematol 11:531–559

    PubMed  CAS  Google Scholar 

  • Stein H, Gerdes J, Schwab U, Lemke H, Mason DY, Ziegler A, Schienle W, Diehl V (1982 b) Identification of Hodgkin and Sternberg-Reed cells as a unique cell type derived from a newly-detected small-cell population. Int J Cancer 30:445–459

    Article  PubMed  CAS  Google Scholar 

  • Steinmann GG (1986) Changes in the human thymus during aging. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Current topics in pathology, vol. 75. Springer, Berlin Heidelberg New York Tokyo, pp 42–88

    Google Scholar 

  • Steinmann GG, Dardenne M, Gerdes J, Müller-Hermelink HK (1985) Autoimmunreaktionen im normalen menschlichen Thymus. Verh Dtsch Ges Pathol 69:578

    Google Scholar 

  • Steinmann GG, Müller-Hermelink HK (1984) Lymphocyte differentiation and its microenvironments in human thymus during aging. Monogr Dev Biol 17:142–155

    PubMed  CAS  Google Scholar 

  • Tamaoki N, Habu S, Kameya T (1971) Thymic lymphoid follicles in autoimmune disease. Histological, histochemical and electronmicroscopic studies. Keio J Med 20:57–68

    PubMed  CAS  Google Scholar 

  • Thomas JA, Willcox HNA, Newsom-Davis J (1982) Immunohistological studies of the thymus in myasthenia gravis. Correlations with clinical state and thymocyte culture response. J Neuroimmunol 3:319–335

    Article  PubMed  CAS  Google Scholar 

  • Tridente G (1985) Immunopathology of the human thymus. Semin Hematol 22:56–67

    PubMed  CAS  Google Scholar 

  • Von Gaudecker B (1986) The development of the human thymus microenvironment. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Springer, Berlin Heidelberg New York Tokyo, pp 1–41

    Google Scholar 

  • Wekerle H, Müller-Hermelink HK (1986) The thymus in myasthenia gravis. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Springer, Berlin Heidelberg New York Tokyo, pp 179–206

    Google Scholar 

  • Wekerle H, Ketelsen U-P, Zum AD, Fulpines BW (1978) Intrathymic pathogenesis of myasthenia gravis: transient expression of acetylcholine receptors on thymus derived myogenic cells. Eur J Immunol 8:579–581

    Article  PubMed  CAS  Google Scholar 

  • Wiersbowsky-Schmeel A, Helpap B, Totovic V, Grouls V (1984) Thymus in myasthenia gravis: a light- and electronmicroscopic study of a case with thymic follicular hyperplasia. Pathol Res Pract 178:323–331

    PubMed  CAS  Google Scholar 

  • Willcox HNA, Newsom-Davis J, Calder LR (1983) Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes. Clin Exp Immunol 54:378–386

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Würzburg, D-8700, Würzburg

    Thomas Kirchner, Thomas von Kügelgen & Hans Konrad Müller-Hermelink

  2. Department of Neurology, University of Würzburg, D-8700, Würzburg

    Berthold Schalke

  3. Max-Planck-Society, Clinical Research Unit for Multiple Sclerosis, D-8700, Würzburg, Federal Republic of Germany

    Arthur Melms

Authors
  1. Thomas Kirchner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Berthold Schalke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arthur Melms
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas von Kügelgen
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Dedicated to Prof. Dr. A. Bohle, Tübingen, on the occasion of his 65th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirchner, T., Schalke, B., Melms, A. et al. Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis. Virchows Archiv B Cell Pathol 52, 237–257 (1986). https://doi.org/10.1007/BF02889966

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02889966

Key words

Search

Navigation