Skip to main content
Log in

Comparative histological studies of regional lymph nodes of 201 melanoma patients

Microscopic features in relation to individual age, site, and metastatic spread

  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

Since May 1968 a total of 2.108 regional lymph nodes (l.n.) dissected from 201 melanoma patients (86 axillary, 107 groin, and 8 neck) have become available for study. The purpose was to detect histological differences between the l.n. of 134 patients lacking and those of 67 patients exhibiting l.n. metastases, histologically verified in 104 of 706 nodes.

The main finding is a more than six-fold increase in number and an elevenfold increase in total area (evaluated by a microscope micrometer) of germinal centers in the lymph follicles of patients with, as compared to those without, l.n. metastases (P≤0.05).

Paracortical areas were found to be diminished in 56.7% of cases with metastatic spread. Accumulations of plasma cells were mainly seen in the nodes of elderly patients (48.4%) and of those exhibiting regional metastases (47.8%).

The observation of numerous and dilated blood vessels in the interfollicular regions noticeably corresponded to the occurrence of lymphatic metastases (P≤0.01), suggesting a “tumor angiogenic factor”. A negative correlation with metastatic involvement was found as to histiocytosis of marginal sinuses and with respect to the observed fibrinoid hyalinosis of pulp vessels (P≤0.01).

The marked hyperplasia of lymph node B-lymphocyte regions as opposed to diminished T-lymphocyte areas prevailing in cases with metastatic melanoma is in accord with findings of humoral immunologic blocking activity and impaired T-cell response in advanced malignant melanoma.

Zusammenfassung

Seit Mai 1968 kamen 2108 regionale Lymphknoten (L.n.) von 201 Melanom-Patienten (86 axilläre, 107 inguinale and 8 cervicale Situs) zur histologischen Auswertung. Ziel der Studie war die Suche nach histologischen Unterschieden zwischen den L.n. von 134 Melanom-Patienten ohne und von 67 Patienten mit regionalen Metastasen, die in 104 von 706 L.n. nachgewiesen wurden.

Als auffallendstes Ergebnis zeigten die Keimzentren in den Lymphfollikeln bei regionaler Metastasierung gegenüber den metastasenfreien Fällen einen mehr als zehnfachen durchschnittlichen Radius (mit dem Mikroskop-Mikrometer ermittelt) und waren über 6mal häufiger (P≤0,05).

Im Gegensatz dazu erschienen die paracorticalen Zonen bei 56,7% der Patienten mit L.n.-Metastasen im Umfang reduziert. Ansammlungen von Plasmazellen wurden bevorzugt in L.n. älterer Patienten (48,4%) und bei regionaler Metastasierung (47,8%) gefunden. Die Beobachtung zahlreicher auffallend dilatierter interfollikulärer Blutgefäße stimmte weitgehend mit dem Vorkommen von L.n.-Metastasen überein (P≤0.01) und legt die Existenz eines angiogenen Tumor-Faktors nahe. Histiocytose der Marginalsinus und beobachtete fibrinoide Hyalinose der Pulpa-Gefäße standen im umgekehrten Häufigkeits-Verhältnis zum Auftreten von L.n.-Metastasen (P≤0,01).

Die Ausgeprägte Hyperplasie der B-lymphocytären Keimzentren und die Involution der T-Lymphocyten-Areale überwiegend bei den Fällen mit L.n.-Metastasen stehen im Einklang mit Befunden einer humoralen immunologischen ≫blocking≪-Aktivität und einer verminderten T-Zellenantwort bei Patientten mit fortgeschrittenem malignen Melanom.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ambus, U.: Specific and nonspecific immunologic reactivity of regional lymph node lymphocytes in human malignancy. Int. J. Cancer14, 291–300 (1974)

    Google Scholar 

  2. Anderson, A. O., Anderson, N. D.: Lymphocyte emigration from high endothelial venules in rat lymph nodes. Immunology31, 731–748 (1976)

    Google Scholar 

  3. Black, M. M., Speer, F. D.: Sinus histiocytosis of lymph nodes in cancer. Surg. Gynecol. Obstet.106, 163–175 (1958)

    Google Scholar 

  4. Blau, J. N.: A comparative study of the microcirculation in the guinea-pig thymus, lymph nodes, and Peyer's patches. Clin. Exp. Immunol.27, 340–347 (1977)

    Google Scholar 

  5. Cahill, R. N. P., Frost, H., Truka, Z.: The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes. J. Exp. Med.143, 870–888 (1976)

    Google Scholar 

  6. Craig, S. W., Cebra, J. J.: Rabbit Peyer's patches, appendix and popliteal lymph node B-lymphocytes: a comparative analysis of their membrane immunoglobulin components and plasma cell precursor potential. J. Immunol.114, 492–502 (1975)

    Google Scholar 

  7. Dabelow, A.: Die Blutgefäßyersorgung der lymphatischen Organe. Anat. Anz. Suppl.87, 179 (1939)

    Google Scholar 

  8. DasGupta, T., McNeer, G.: The incidence of metastasis to accessible lymph nodes from melanoma of the trunk and extremities — its therapeutic significance. Cancer17, 897–911 (1964)

    Google Scholar 

  9. DasGupta, T.: Results of treatment of 269 patients with primary cutaneous melanoma: A five-year prospective study. Ann. Surg.186, 201–209 (1977)

    Google Scholar 

  10. Daveau, M., Pavie-Fischer, J., Rivat, L., Rivat, C., Ropartz, C., Peter, H. H., Cesarini, J. I., Kourilsky, F. M.: Étude des IgG dans les sérums des sujets porteurs de mélanomes. Ann. Derm. Venereol.104, 458–460 (1977)

    Google Scholar 

  11. Deakin, A. S.: Model for initial vascular patterns in melanoma transplants. Growth40, 191–201 (1976)

    Google Scholar 

  12. Embleton, M. J., Price, M. R.: Detection and partial purification of melanoma-associated antigen. Br. J. Dermatol.99 (Suppl. 16) 19 (1978)

    Google Scholar 

  13. Fidler, I. J., McWilliams, R. W., Bech-Nielsen, S., Budmen, M. B.: Role of the regional lymph node in neoplasia: cellular mediated reactivity in vitro by autologous regional or distal lymph nodes or peripheral blood lymphocytes of dogs with spontaneous neoplasms. Immunol. Communic.4, 325–335 (1975)

    Google Scholar 

  14. Folkman, J., Merler, E., Abernathy, C., Williams, G.: Isolation of a tumor factor responsible for angiogenesis. J. Exp. Med.133, 275–288 (1971)

    Google Scholar 

  15. Folkman, J.: Relation of endothelial proliferation to tumor growth. In: Internat. review of experimental pathology. Richter, G. W., Epstein, N. A. (eds.), Vol. XVI. New York, London: Academic Press 1976

    Google Scholar 

  16. Frey, J. R., Wenk, P.: Experimentelle Untersuchungen zur Pathogenese des Kontaktekzems. Dermatologica (Basel)112, 265–305 (1956)

    Google Scholar 

  17. Frey, J. R., Wenk, P.: Über die Funktion der regionalen Lymphknoten bei der Entstehung des Dinitrochlorbenzol-Kontaktekzems am Meerschweinchen. Dermatologica (Basel)116, 243–259 (1958)

    Google Scholar 

  18. Fritz, J., Grond, K., Tilz, G. P.: Zur cellulären Immunität beim Melanomalignom. Arch. Dermatol. Res.255, 203–209 (1976)

    Google Scholar 

  19. Gorton, G., Linell, F.: Acta Radiol. (Stockh.)47, 381 (1957)

    Google Scholar 

  20. Gowans, J. L., Knight, E. J.: The route of recirculation of lymphocytes in the rat. Proc. Roy. Soc. B159, 257 (1964)

    Google Scholar 

  21. Gresham, G. A., Ackerley, A. G.: J. Clin. Pathol.11, 244 (1958)

    Google Scholar 

  22. Hay, J. B., Hobbs, B. B.: The flow of blood to lymph nodes and its relation to lymphocyte traffic and the immune response. J. Exp. Med.145, 31–44 (1977)

    Google Scholar 

  23. Heite, H.-J.: Prognose anhand der Absterbekurve in Abhängigkeit von Irritation, Wachstum und Oberflächengestalt des Primärherdes. Arch. Dermatol. Res.244, 200–205 (1972)

    Google Scholar 

  24. Hellström, I., Warner, G. A., Hellström, K. E.: Sequential studies on cell-mediated tumor immunity and blocking serum activity in ten patients with malignant melanoma. Int. J. Cancer11, 280 (1973)

    Google Scholar 

  25. Heppner, G. H., Stolbach, L., Byrne, M., Cummings, F. J., McDonough, E., Calabresi, P.: Cell-mediated and serum blocking reactivity to tumor antigens in patients with malignant melanoma. Int. J. Cancer11, 245–260 (1973)

    Google Scholar 

  26. Herman, P. G., Yamamoto, I., Mellins, H. Z.: Blood microcirculation in the lymph node during the primary response. J. Exp. Med.136, 697 (1972)

    Google Scholar 

  27. Hornstein, O. P., Weidner, F.: Untersuchungen zur prognostischen Bedeutung der “Stromareaktion” beim malignen Melanom. I. Vascularisation und Prognose. Virchows Arch. (Pathol. Anat.)359, 67–76 (1973)

    Google Scholar 

  28. Jaffe, E. S., Shevach, E. M., Frank, M. M., Berard, C. W., Green, I.: Nodular lymphoma-evidence for origin from follicular B-lymphocytes. N. Engl. J. Med.290, 813–819 (1974)

    Google Scholar 

  29. Kristensen, E., Langvad, E., Reimann R.: Humoral immunity in malignant skin melanoma. Isolation of melanoma specific IgG from melanoma metastases. Eur. J. Cancer12, 945–950 (1976)

    Google Scholar 

  30. Lamm, M. E.: Distribution of IgA-bearing cells among lymphoid tissues. Adv. Immunol.22, 228 (1976)

    Google Scholar 

  31. Leeuwen, A. W. F. M. van, Meijer, C. J. L. M., Man J. C. H. de: T-cell membrane characteristics of “mycosis cells” in the skin and lymph node. J. Invest. Dermatol.65, 367–369 (1975)

    Google Scholar 

  32. Leiber, B.: Der menschliche Lymphnoten. München, Berlin: Urban u. Schwarzenberg 1961

    Google Scholar 

  33. Lennert, K.: Lymphknoten. Diagnostik in Schnitt und Ausstrich. Bandteil A: Cytologie und Lymphadenitis. In: Handb. der speziellen pathologischen Anatomie und Histologie, Uehlinger, E. (Hrsg.), Bd. I/III. Berlin, Göttingen, Heidelberg, New York: Springer 1961

    Google Scholar 

  34. Macher, E.: Die Reaktion der regionären Lymphknoten beim tierexperimentellen allergischen Kontaktekzem. II. Histologische Untersuchungen. Hautarzt13, 126–131 (1962)

    Google Scholar 

  35. Miller, E. E., Rosato, F. E., Brown, A. S., Moskovitz, A., Johnson, J.: Cytotoxicity reactions during immunotherapy of melanoma with neuraminidase altered autologous tumor cells. J. Surg. Oncology8, 31–34 (1976)

    Google Scholar 

  36. Mackie, R. M., Spilg, G. S., Thomas, C. E., Cochran, A. J.: Cellmediated immunity in patients with malignant melanoma. Br. J. Dermatol.87, 523–528 (1972)

    Google Scholar 

  37. Müller-Hermelink, H. K., Kaiserling, E., Lennert, K.: Pseudofollikuläre Nester von Plasmazellen (eines besonderen Typs?) in der paracorticalen Pulpa menschlicher Lymphknoten. Virchows Arch. (Zellpathol.)14, 47–56 (1973)

    Google Scholar 

  38. Murray, E., McCarthy, W. H., Hersey, P.: Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients. Br. J. Cancer36, 7–14 (1977)

    Google Scholar 

  39. Nadel, E. M., Ackerman, L. V.: Am. J. Clin. Pathol.20, 952 (1950)

    Google Scholar 

  40. Nödl, F.: Lamellenkörperchen im Lymphknotenhilus und ihre Bedeutung für die Melanommetastasierung. Arch. Dermatol. Res.253, 119–124 (1975)

    Google Scholar 

  41. Nödl, F.: Über die Filterwirkung der Lymphknoten bei der Melanommetastasierung. Arch. Dermatol. Res.255, 237–243 (1976)

    Google Scholar 

  42. O'Toole, C., Saxon, A., Bohrer, R.: Human lymph node lymphocytes fail to effect lysis of antibodycoated target cells. Clin. Exp. Immunol.27, 165–171 (1977)

    Google Scholar 

  43. Rangel, D. M., Golub, S. H., Morton, D. L.: Demonstration of lymphocyte blastogenesis-inhibiting factors in sera of melanoma patients. Surgery82, 224–232 (1977)

    Google Scholar 

  44. Reich, H.: Hautkrebs und regionale Lymphknoten. In: Dermatologie und Venerologie, Gottron, H. A., Schönfeld, W. (Hrsg.), Erg.bd., S. 115–119. Stuttgart: Thieme 1970

    Google Scholar 

  45. Rydgren, L., Norberg, B., Macklenburg, C. v., Hakansson, C.-H., Söderström, N.: Lymphocyte locomotion. III. Ultrastructural studies of the lymphocyte traffic over the postcapillary venules of rat lymph nodes. Lymphology9, 150–154 (1976)

    Google Scholar 

  46. Seibert, E., Sorg, C., Happle, R., Macher, E.: Membrane associated antigens of human malignant melanoma. III. Specificity of human sera reacting with cultured melanoma cells. Int. J. Cancer19, 172–178 (1977)

    Google Scholar 

  47. Shevach, E. M., Jaffe, E. S., Green, I.: Receptors for complement and immunoglobulin on human and animal lymphoid cells. Transplant Rev.16, 3–28 (1973)

    Google Scholar 

  48. Silveira, N. P. A., Mendes, N. F., Tolnai, M. E. A.: Tissue localization of two populations of human lymphocytes distinguished by membrane receptors. J. Immunol.108, 1456–1460 (1972)

    Google Scholar 

  49. Silverman, N. A., Alexander, J. C., Jr., Potvin, C., Chretien, P. B.: In vitro lymphocyte reactivity and T cell levels in patients with melanoma: correlations with clinical and pathological stage. Surgery79, 332–339 (1976)

    Google Scholar 

  50. Sjörgen, N. O., Hellström, I., Bansal, C., Warner, G. A., Hellström, K. E.: Elution of “blocking factors” from human tumors, capable of abrogating tumor-cell destruction by specifically immune lymphocytes. Int. J. Cancer9, 274–283 (1972)

    Google Scholar 

  51. Stein, H.: Klassifikation der malignen Non-Hodgkin-Lymphome aufgrund gemeinsamer morphologischer und immunologischer Merkmale zwischen normalen und neoplastischen lymphatischen Zellen. Immun. Infekt.4, 52–69 (1976)

    Google Scholar 

  52. Stein, H., Siemssen, U., Lennert, K.: Complement receptor subtypes C3b and C3d in lymphatic tissue and follicular lymphoma. Br. J. Cancer37, 520–529 (1978)

    Google Scholar 

  53. Stingl, G., Wolff, K., Diem, E., Baumgartner, G., Knapp, W.: In situ identification of lymphoreticular cells in benign and malignant infiltrates by membrane receptor sites. J. Invest. Dermatol.69, 231–235 (1977)

    Google Scholar 

  54. Storck, H.: Zur Klinik und Therapie des malignen Melanoms. Hautarzt21, 187–194 (1970)

    Google Scholar 

  55. Suter, L., Sorg, C., Macher, E.: Membrane-associated antigens of human malignant melanoma. II. Leucocyte migration studies with formalin fixed human melanoma cells. Z. Immun. Forsch.151, 242–249 (1976)

    Google Scholar 

  56. Vose, B. M., Vánky, F., Argov, S., Klein, E.: Natural cytotoxicity in man: activity of lymph node and tumor-infiltrating lymphocytes. Eur. J. Immunol.7, 753–757 (1977)

    Google Scholar 

  57. Weidner, F., Hornstein, O.P., Hermanek, P., Wutz, G.: Early metastases in regional lymph nodes and prognosis of malignant melanoma. Arch. Dermatol. Res.256, 167–177 (1976)

    Google Scholar 

  58. Weidner, F., Hornstein, O. P.: Untersuchungen zur prognostischen Bedeutung der “Stromareaktion” beim malignen Melanom. II. Entzündliches Infiltrat und Prognose. Virchows Arch. (Pathol. Anat.)359, 77–85 (1973)

    Google Scholar 

  59. Weidner, F., Horstein, O. P.: Das Problem der regionalen Lymphknoten-Metastasierung beim malignen Melanom. Arch. Dermatol. Forsch.245, 50–62 (1972)

    Google Scholar 

  60. Zeromski, J., Gorny, M. K., Wruk, M., Sapula, J.: Behaviour of local and systemic immunoglubins in patients with lung cancer. Int Archs. Allergy Appl. Immunol.49, 548–563 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to Prof. Dr. G. Stüttgen to the 60th anniversary of his birthday

Supported by “Deutsche Forschungs-Gemeinschaft” (We 766/1)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weidner, F. Comparative histological studies of regional lymph nodes of 201 melanoma patients. Arch Dermatol Res 266, 161–175 (1979). https://doi.org/10.1007/BF00694625

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00694625

Key words

Schlüsselwörter

Navigation