Summary
Two malignant lymphomas were investigated. They were light microscopically characterized by a large number of PAS-positive cytoplasmic inclusions. Electron microscopically these inclusions were represented by electron-dense condensates lying in distended cisternae of the rough endoplasmatic reticulum. Immunochemical analyses revealed a high increase of IgM in the tumor tissue homogenates, but no macroglobulinemia in the sera. This indicates that the tumor cells produced but could not secrete IgM and that the cytoplasmic inclusions represented accumulated IgM.
The first lymphoma showed a wide cytological spectrum from small lymphocytoid cells to cells rich in ergastoplasm. About 8–10% of these tumor cells contained cytoplasmic inclusions. The tumor was therefore cytologically similar to Waldenström’s disease, but distinguished from it by the lack of macroglobulinemia. In the second case the tumor consisted of mostly large cells with large nuclei and a poorly developed endoplasmatic reticulum but numerous polysomes. IgM-condensates were found exclusively in distended cisternae of the perinuclear space. These tumor cells were similar to immunoblasts in both the cytological features and site of Ig-production.
In Case 1 there were no morphological clues for the cause of the secretory defect. IgM extracted from the tumor was electrophoretically identified as mainly 8 S IgM-monomer. We therefore assume that the lack of secretion was caused by a defect in the polymerisation mechanism. For Case 2 we conclude that the lack of secretion was based on a disturbance of the IgM-transport from the perinuclear space to the Golgi apparatus due to the nearly complete absence of endoplasmatic reticulum.
The two tumors represent a previously not well known group of B-cell lymphomas consisting of secretory cells which accumulate but do not secrete immunoglobulins.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Literature
Avrameas, S.: Immunoenzyme techniques: Enzymes as markers for the localization of antigens and antibodies. Int. Rev. Cytol.27, 349–385 (1970)
Avrameas, S., Leduc, E. H.: Detection of simultaneous antibody synthesis in plasma cells and specialized lymphocytes in rabbit lymph nodes. J. exp. Med.131, 1137–1168 (1970)
Bush, S. T., Swedlund, H. A., Gleich, G. J.: Low molecular weight IgM in human sera. J. Lab. clin. Med.73, 194–201 (1969)
Davis, B. J.: Disc electrophoresis. II. Method and application to human serum proteins. Ann. N.Y. Acad. Sci.121, 404–427 (1964)
DiGuglielmo, R.: Unusual morphologic and humoral conditions in the field of plasmocytomas and M-dysproteinemia. Acta med. scand.179 (Suppl. 445), 206–211 (1966)
Fröland, S. S., Natvig, J. B.: Surface-bound immunoglobulin on lymphocytes from normal and immunodeficient humans. Scand. J. Immunol. 1, 1–12 (1972)
Gonatas, N. K., Antoine, J.-C., Stieber, A., Avrameas, S.: Surface immunoglobulins of thymus and lymph node cells demonstrated by the peroxidase coupling technique. Lab. Invest.26, 253–261 (1972)
Greenwood, F. C., Hunter, W. M., Glover, J. S.: The preparation of 131 J. labeled human growth hormone of high specific radioactivity. Biochem. J.89, 114–123 (1963)
Grey, H. M., Rabellino, E., Pirofsky, B.: Immunoglobulins on the surface of lymphocytes. IV. Distribution in hypo-γ-globulineamia, cellular immune deficiency, and chronic lymphatic leukemia. J. clin. Invest.50, 2368–2375 (1971)
Hurez, D., Flandrin, G., Preud’homme, J. L., Seligmann, M.: Unreleased intracellular monoclonal macroglobulin in chronic lymphocytic leukemia. Clin. exp. Immunol.10, 223–234 (1972)
Hurez, D., Preud’homme, J. L., Seligmann, M.: Intracellular “monoclonal” immunoglobulin in non-secretory human myeloma. J. Immunol.104, 263–264 (1970)
Kaiserling, E.: Verzweigte tubuläre Cytoplasmaeinschlüsse im menschlichen Lymphknoten. Beitr. Path.147, 237–248 (1972)
Kincade, P. W., Lawton, A. R., Cooper, M. D.: Restriction of surface immunoglobulin determinants to lymphocytes of the plasma cell line. J. Immunol.106, 1421–1423 (1971)
Krauss, S., Sokal, J. E.: Paraproteinemia in the lymphomas. Amer. J. Med.40, 400–413 (1966)
Leduc, E. H., Avrameas, S., Bouteille, M.: Ultrastructural localization of antibody in differentiating plasma cells. J. exp. Med.127, 109–118 (1968).
Matter, A., Lisowska-Bernstein, B., Ryser, J. E., Lamelin, J.-P., Vassalli, P.: Mouse thymusindependent and thymus-derived lymphoid cells. II Ultrastructural studies. J. exp. Med.136, 1008–1030 (1972)
McConahey, P. J., Dixon, F. J.: A method for trace jodation of proteins for immunologic studies. Int. Arch. Allergy29, 185–189 (1966)
Moore, D. F., Migliore, P. J., Shullenberger, C. C., Alexanian, R.: Monoclonal macroglobulinemia in malignant lymphoma. Ann. intern. Med.72, 43–47 (1970)
Mori, Y., Lennert, K.: Electron microscopic atlas of lymph node cytology and pathology. Berlin-Heidelberg-New York: Springer 1969
Ornstein, L.: Disc electrophoresis. Ann. N.Y. Acad. Sci.121, 321–349 (1964)
Osserman, E. F., Takatsuki, K.: Plasma cell myeloma: Gamma globulin synthesis and structure. Medicine (Baltimore)42, 357–384 (1963)
Ouchterlony, Ö.: Progress in allergy. Ed.: P. Kallos. Vol. 5. Basel-New York: S. Karger 1958
Panijel, J., Delamette, F., Leneveu, M.: Cellular and subcellular study of the in vitro immune response. Europ. J. Immunol. 1, 87–97 (1971).
Parkhouse, R. M. E., Askonas, B. A.: Immunoglobulin M biosynthesis. Intracellular accumulation of 7 S subunits. Biochem. J.115, 163–169 (1969).
Pernis, B., Forni, L., Amante, L.: Immunoglobulins as cell receptors. Ann. N.Y. Acad. Sci.190, 420–431 (1971)
Preud’homme, J. L., Hurez, D., Seligmann, M.: Immunofluorescence studies in Waldenström’s macroglobulinemia. Rev. europ. Étud. clin. et biol.15, 1127–1131 (1970)
Preud’homme, J. L., Seligmann, M.: Immunoglobulins on the surface of lymphoid cells in Waldenström’s macroglobulinemia. J. clin. Invest.51, 701–705 (1972a)
Preud’homme, J. L., Seligmann, M.: Surface bound immunoglobulins as a cell marker in human lymphoproliferative diseases. Blood40, 777–794 (1972 b)
Rabellino, E., Grey, H. M.: Immunoglobulins on the surface of lymphocytes. III. Bursal origin of surface immunoglobulins on chicken lymphocytes. J. Immunol.106, 1418–1420 (1971)
Raff, M. C., Sternberg, M., Taylor, R. B.: Immunoglobulin determinants on the surface of mouse lymphoid cells. Nature (Lond.)225, 553–554 (1970)
Sherr, J. C., Schenkein, I., Uhr, J. W.: Synthesis and intracellular transport of immunoglobulin in secretory and nonsecretory cells. Ann. N.Y. Acad. Sci.190, 250–267 (1971)
Stein, H., Kaiserling, E., Lennert, K.: Neue Gesichtspunkte zur Systematik maligner Lymphome auf dem Boden immunchemischer Analysen. In: A. Stacher, Hrsg., Leukämien und maligne Lymphome. Pathophysiologie, Klinik, Chemound Immunotherapie, S. 195–201. München-Berlin-Wien: Urban & Schwarzenberg 1972a
Stein, H., Lennert, K., Parwaresch, M. R.: Malignant lymphomas of B-cell type. Lancet 1972b II, 855–857
Stein, H., Parwaresch, M. R.: Lokalisation der IgM-Fraktion in diskontinuierlichen Polyacrylamid-Elektrophoresesäulen. Blut23, 104–112 (1971)
Vitetta, E. S., Baur, S., Uhr, J. W.: Cell surface immunoglobulin. II. Isolation and characterisation of immunoglobulin from mouse splenic lymphocytes. J. exp. Med.134, 242–264 (1971)
Vitetta, E. S., Bianco, C., Nussenzweig, V., Uhr, J. W.: Cell surface immunoglobulin. IV. Distribution among thymocytes, bone marrow cells, and their derived populations. J. exp. Med.136, 81–93 (1972)
Ward, A. M., Shortland, J. R., Darke, C. S.: Lymphosarkoma of the lung with monoclonal (IgM) gammopathy. Cancer (Philad.)27, 1009–1028 (1971)
Author information
Authors and Affiliations
Additional information
Supported by the Deutsche Forschungsgemeinschaft.
Rights and permissions
About this article
Cite this article
Kaiserling, E., Stein, H. & Lennert, K. IgM-producing malignant lymphomas without macroglobulinemia. Morphological and immunochemical findings. Virchows Arch. Abt. B Zellpath. 14, 1–18 (1973). https://doi.org/10.1007/BF02889169
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02889169