Abstract
The authors report an immunohistologic study of primary thymomas from 23 cases with myasthenia gravis (MG) and 7 without. Typical T6+ cortical thymocytes were usually abundant. Most epithelial cells initially appeared to be of cortical type, too, though many bore subcapsular markers in most samples. However, two-color immunofluorescence revealed unexpected heterogeneity, numerous epithelial cells simultaneously expressing some or all of the markers of both these subsets (even in two pleural metastases). It is inferred that there is a common tumor stem cell whose normal counterpart may be related to the rare patches of similar phenotype in the cortex in control samples. The authors could detect no major differences in 5 of 7 samples from nonmyasthenics; thus, most thymoma cases may risk the development of MG. Finally, thymomas from 6 of 7 further MG cases pretreated with corticosteroids showed very few cortical thymocytes, and the (phenotypically similar) epithelium was more obvious.
Full text
PDF













Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrews P. W. Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev Biol. 1984 Jun;103(2):285–293. doi: 10.1016/0012-1606(84)90316-6. [DOI] [PubMed] [Google Scholar]
- Bofill M., Janossy G., Willcox N., Chilosi M., Trejdosiewicz L. K., Newsom-Davis J. Microenvironments in the normal thymus and the thymus in myasthenia gravis. Am J Pathol. 1985 Jun;119(3):462–473. [PMC free article] [PubMed] [Google Scholar]
- Chan W. C., Zaatari G. S., Tabei S., Bibb M., Brynes R. K. Thymoma: an immunohistochemical study. Am J Clin Pathol. 1984 Aug;82(2):160–166. doi: 10.1093/ajcp/82.2.160. [DOI] [PubMed] [Google Scholar]
- Chilosi M., Iannucci A. M., Pizzolo G., Menestrina F., Fiore-Donati L., Janossy G. Immunohistochemical analysis of thymoma. Evidence for medullary origin of epithelial cells. Am J Surg Pathol. 1984 Apr;8(4):309–318. doi: 10.1097/00000478-198404000-00009. [DOI] [PubMed] [Google Scholar]
- Chilosi M., Iannucci A., Fiore-Donati L., Tridente G., Pampanin M., Pizzolo G., Ritter M., Bofill M., Janossy G. Myasthenia gravis: immunohistological heterogeneity in microenvironmental organization of hyperplastic and neoplastic thymuses suggesting different mechanisms of tolerance breakdown. J Neuroimmunol. 1986 May;11(3):191–204. doi: 10.1016/0165-5728(86)90003-2. [DOI] [PubMed] [Google Scholar]
- Collins M. K., Tanigawa G., Kissonerghis A. M., Ritter M., Price K. M., Tonegawa S., Owen M. J. Regulation of T-cell receptor gene expression in human T-cell development. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4503–4507. doi: 10.1073/pnas.82.13.4503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujii Y., Monden Y., Nakahara K., Hashimoto J., Kawashima Y. Antibody to acetylcholine receptor in myasthenia gravis: production by lymphocytes from thymus or thymoma. Neurology. 1984 Sep;34(9):1182–1186. doi: 10.1212/wnl.34.9.1182. [DOI] [PubMed] [Google Scholar]
- Gilhus N. E., Aarli J. A., Christensson B., Matre R. Rabbit antiserum to a citric acid extract of human skeletal muscle staining thymomas from myasthenia gravis patients. J Neuroimmunol. 1984 Nov;7(1):55–64. doi: 10.1016/s0165-5728(84)80006-5. [DOI] [PubMed] [Google Scholar]
- Haynes B. F. The human thymic microenvironment. Adv Immunol. 1984;36:87–142. doi: 10.1016/s0065-2776(08)60900-1. [DOI] [PubMed] [Google Scholar]
- Hirst E., Robertson T. I. The syndrome of thymoma and erythroblastopenic anemia. A review of 56 cases including 3 case reports. Medicine (Baltimore) 1967 May;46(3):225–264. doi: 10.1097/00005792-196705000-00001. [DOI] [PubMed] [Google Scholar]
- ISHIDATE M., METCALF D. THE PATTERN OF LYMPHOPOIESIS IN THE MOUSE THYMUS AFTER CORTISONE ADMINISTRATION OR ADRENALECTOMY. Aust J Exp Biol Med Sci. 1963 Dec;41:637–649. doi: 10.1038/icb.1963.53. [DOI] [PubMed] [Google Scholar]
- Janossy G., Bofill M., Poulter L. W., Rawlings E., Burford G. D., Navarrete C., Ziegler A., Kelemen E. Separate ontogeny of two macrophage-like accessory cell populations in the human fetus. J Immunol. 1986 Jun 15;136(12):4354–4361. [PubMed] [Google Scholar]
- Kao I., Drachman D. B. Thymic muscle cells bear acetylcholine receptors: possible relation to myasthenia gravis. Science. 1977 Jan 7;195(4273):74–75. doi: 10.1126/science.831257. [DOI] [PubMed] [Google Scholar]
- Kirchner T., Hoppe F., Müller-Hermelink H. K., Schalke B., Tzartos S. Acetylcholine receptor epitopes on epithelial cells of thymoma in myasthenia gravis. Lancet. 1987 Jan 24;1(8526):218–218. doi: 10.1016/s0140-6736(87)90032-8. [DOI] [PubMed] [Google Scholar]
- Lauriola L., Piantelli M., Carbone A., Dina M. A., Scoppetta C., Musiani P. Subpopulations of lymphocytes in human thymomas. Clin Exp Immunol. 1979 Sep;37(3):502–506. [PMC free article] [PubMed] [Google Scholar]
- Levine G. D., Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum Pathol. 1978 Sep;9(5):495–515. doi: 10.1016/s0046-8177(78)80131-2. [DOI] [PubMed] [Google Scholar]
- McFarland E. J., Scearce R. M., Haynes B. F. The human thymic microenvironment: cortical thymic epithelium is an antigenically distinct region of the thymic microenvironment. J Immunol. 1984 Sep;133(3):1241–1249. [PubMed] [Google Scholar]
- McMichael A. J., Pilch J. R., Galfré G., Mason D. Y., Fabre J. W., Milstein C. A human thymocyte antigen defined by a hybrid myeloma monoclonal antibody. Eur J Immunol. 1979 Mar;9(3):205–210. doi: 10.1002/eji.1830090307. [DOI] [PubMed] [Google Scholar]
- Mokhtar N., Hsu S. M., Lad R. P., Haynes B. F., Jaffe E. S. Thymoma: lymphoid and epithelial components mirror the phenotype of normal thymus. Hum Pathol. 1984 Apr;15(4):378–384. doi: 10.1016/s0046-8177(84)80037-4. [DOI] [PubMed] [Google Scholar]
- Müller-Hermelink H. K., Marino M., Palestro G. Pathology of thymic epithelial tumors. Curr Top Pathol. 1986;75:207–268. doi: 10.1007/978-3-642-82480-7_7. [DOI] [PubMed] [Google Scholar]
- Nakao Y., Matsumoto H., Miyazaki T., Nishitani H., Ota K., Fujita T., Tsuji K. Gm allotypes in myasthenia gravis. Lancet. 1980 Mar 29;1(8170):677–680. [PubMed] [Google Scholar]
- Namba T., Brunner N. G., Grob D. Myasthenia gravis in patients with thymoma, with particular reference to onset after thymectomy. Medicine (Baltimore) 1978 Sep;57(5):411–433. doi: 10.1097/00005792-197809000-00002. [DOI] [PubMed] [Google Scholar]
- Osserman K. E., Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med. 1971 Nov-Dec;38(6):497–537. [PubMed] [Google Scholar]
- Pierce G. B., Nakane P. K., Martinez-Hernandez A., Ward J. M. Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J Natl Cancer Inst. 1977 May;58(5):1329–1345. doi: 10.1093/jnci/58.5.1329. [DOI] [PubMed] [Google Scholar]
- Savino W., Manganella G., Verley J. M., Wolff A., Berrih S., Levasseur P., Binet J. P., Dardenne M., Bach J. F. Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex. J Clin Invest. 1985 Sep;76(3):1140–1146. doi: 10.1172/JCI112069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Souadjian J. V., Enriquez P., Silverstein M. N., Pépin J. M. The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med. 1974 Aug;134(2):374–379. [PubMed] [Google Scholar]
- VAN DER GELD H., FELTKAMP T. E., OOSTERHUIS H. J. REACTIVITY OF MYASTHENIA GRAVIS SERUM GAMMA-GLOBULIN WITH SKELETAL MUSCLE AND THYMUS DEMONSTRATED BY IMMUNOFLUORESCENCE. Proc Soc Exp Biol Med. 1964 Mar;115:782–785. doi: 10.3181/00379727-115-29037. [DOI] [PubMed] [Google Scholar]
- Vincent A. Immunology of acetylcholine receptors in relation to myasthenia gravis. Physiol Rev. 1980 Jul;60(3):756–824. doi: 10.1152/physrev.1980.60.3.756. [DOI] [PubMed] [Google Scholar]
- Weissman I. L. Thymus cell maturation. Studies on the origin of cortisone-resistant thymic lymphocytes. J Exp Med. 1973 Feb 1;137(2):504–510. doi: 10.1084/jem.137.2.504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wekerle H., Ketelsen U. P. Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet. 1977 Mar 26;1(8013):678–680. doi: 10.1016/s0140-6736(77)92118-3. [DOI] [PubMed] [Google Scholar]
- Willcox H. N., Newsom-Davis J., Calder L. R. Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes. Clin Exp Immunol. 1983 Nov;54(2):378–386. [PMC free article] [PubMed] [Google Scholar]
- de Maagd R. A., MacKenzie W. A., Schuurman H. J., Ritter M. A., Price K. M., Broekhuizen R., Kater L. The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. Immunology. 1985 Apr;54(4):745–754. [PMC free article] [PubMed] [Google Scholar]
- van de Wijngaert F. P., Kendall M. D., Schuurman H. J., Rademakers L. H., Kater L. Heterogeneity of epithelial cells in the human thymus. An ultrastructural study. Cell Tissue Res. 1984;237(2):227–237. doi: 10.1007/BF00217140. [DOI] [PubMed] [Google Scholar]
- van der Kwast T. H., van Vliet E., Cristen E., van Ewijk W., van der Heul R. O. An immunohistologic study of the epithelial and lymphoid components of six thymomas. Hum Pathol. 1985 Oct;16(10):1001–1008. doi: 10.1016/s0046-8177(85)80277-x. [DOI] [PubMed] [Google Scholar]
- von Gaudecker B. The development of the human thymus microenvironment. Curr Top Pathol. 1986;75:1–41. doi: 10.1007/978-3-642-82480-7_1. [DOI] [PubMed] [Google Scholar]





