Lymphatic Metastasis of Neoplasms

  • Ian Carr
  • Jean Carr


Human cancers commonly metastasize by the lymphatics to draining lymph nodes. The existence of lymphatic vessels has been known since the observations of Aselli in 1622 and the fact that cancer can spread to lymph nodes was “well-known”to Pearson in 1793 (reviewed by Mayerson, 1969; Onuigbo, 1972). Recent advances in our knowledge of metastasis have been founded largely on studies of hematogenous metastasis (Fidler et al. , 1978; Roos and Dingemans, 1979; Poste and Fidler, 1980). Less work has been done on lymphatic metastasis (reviewed by van de Velde and Carr, 1977; Carr and Carr, 1980).


Lymph Node Lymphatic Vessel Drain Lymph Node Lymphatic Metastasis Popliteal Lymph Node 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Becker, E. F., 1978, Patterns of spontaneous metastasis of transplantable hepatocellular carcinomas, Cancer Res. 38:163.PubMedGoogle Scholar
  2. Bogden, A. E., and Esber, H. J., 1978, Influence of surgery, irradiation, chemotherapy, and immu-notherapy on growth of a metastasizing rat mammary adenocarcinoma, Natl. Cancer Inst. Monogr. 49:97.PubMedGoogle Scholar
  3. Bogden, A. E., Esber, H. J., Taylor, D. J., and Gray, J. H., 1974, Comparative study on the effects of surgery, chemotherapy, and immunotherapy, alone and in combination, on metastases of the 13762 mammary adenocarcinoma, Cancer Res. 34:1627.PubMedGoogle Scholar
  4. Butler, T. P., Grantham, F. H., and Gullino, P. M., 1975, Bulk transfer of fluid in the interstitial compartment of mammary tumors, Cancer Res. 35:3084.PubMedGoogle Scholar
  5. Carr, I., 1977, The passage of macrophages across lymphatic walls by reverse diapedesis:An ultrastructural study, J. Reticuloendothelial Soc. 6:397.Google Scholar
  6. Carr, I., 1980, The pathologist’s role in interpreting metastatic lymph node disease, in:Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 138–154, Hall, Boston.Google Scholar
  7. Carr, I., and Carr, J., 1980, Experimental lymphatic invasion and metastasis, in:Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 41–73, Hall, Boston.Google Scholar
  8. Carr, I., and McGinty, F., 1974, Lymphatic metastasis and its inhibition:An experimental model, J. Pathol. 113:85.PubMedCrossRefGoogle Scholar
  9. Carr, I., and McGinty, F., 1976, Neoplastic invasion and metastasis within the lymphoreticular system, Adv. Exp. Med. Biol. 73(B):319.PubMedGoogle Scholar
  10. Carr, I., McGinty, F., Potter, C., and Westby, S., 1974a, Lymphatic metastasis of transplantable animal neoplasms, Experientia 30:185.PubMedCrossRefGoogle Scholar
  11. Carr, I., Underwood, J. C. E., McGinty, F., and Wood, P., 1974b, The ultrastructure of the local lymphoreticular response to an experimental neoplasm, J. Pathol. 113:175.PubMedCrossRefGoogle Scholar
  12. Carr, I., McGinty, F., and Norris, P., 1976a, The fine structure of neoplastic invasion:Invasion of liver, skeletal muscle and lymphatic vessels by the Rd/3 tumour, J. Pathol. 118:91.PubMedCrossRefGoogle Scholar
  13. Carr, I., Price, P., and Westby, S., 1976b, The effects of tumor extract on macrophage proliferation in lymph nodes, J. Pathol. 120:251.PubMedCrossRefGoogle Scholar
  14. Carr, J., Carr, I., Dreher, B., and Betts, K., 1980, Lymphatic metastasis:Invasion of lymphatic vessels and efflux of tumour cells in the afferent popliteal lymph as seen in the Walker rat carcinoma, J. Pathol. 132:287.PubMedCrossRefGoogle Scholar
  15. Carr, I., Carr, J., and Dreher, B., 1981, Lymphatic metastasis of mammary adenocarcinoma:An experimental study in the rat with a brief review of the literature, Invasion Metastasis 1:34–53.PubMedGoogle Scholar
  16. Carter, R. L., 1978a, General pathology of the metastatic process, in:Secondary Spread of Cancer (R. W. Baldwin, ed.), pp. 1–52, Academic Press, New York.Google Scholar
  17. Carter, R. L., 1978b, Lymphoreticular reactions and the metastatic process, in: Secondary Spread of Cancer (R. W. Baldwin, ed.), pp. 53–72, Academic Press, New York.Google Scholar
  18. Casley-Smith, J. R., 1976, The functioning and interrelationships of blood capillaries and lymphatics, Experientia 32:1.PubMedCrossRefGoogle Scholar
  19. Crile, G., Jr., 1968, The effect on metastasis of removing or irradiating regional nodes of mice, Surg. Gynecol. Obstet. 126:1270.PubMedGoogle Scholar
  20. Crile, G., Jr., Isbister, W., and Deodhar, S. D., 1971, Demonstration that large metastases in lymph nodes disseminate cancer cells to blood and lungs, Cancer 28:657.PubMedCrossRefGoogle Scholar
  21. Fidler, I. J., and Hoover, H. C., 1980, Lymph node and visceral metastasis of cloned murine fibrosar-coma cell lines, in: Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 80–90, Hall, Boston.Google Scholar
  22. Fidler, I. J., and Kripke, K. L., 1977, Metastasis results from preexisting variant cells within a malignant tumor, Science 197:893.PubMedCrossRefGoogle Scholar
  23. Fidler, I. J., Gersten, D. M., and Hart, I. R., 1978, The biology of cancer invasion and metastasis, Adv. Cancer Res. 28:149.PubMedCrossRefGoogle Scholar
  24. Finlay-Jones, J. J., Bartholomaeus, W. N., Fimmel, P. J., Keast, D., and Stanley, N. F., 1980, Biologic and immunologic studies on a murine model of regional lymph node metastasis, J. Natl. Cancer Inst. 64:1363.PubMedGoogle Scholar
  25. Fisher, B., and Fisher, E. R., 1966, Transmigration of lymph nodes by tumor cells, Science 152:1397.PubMedCrossRefGoogle Scholar
  26. Franchi, G., Innocenti, I. R.-D., Rosso, R., and Garattini, S., 1968, Lymph-node metastases after intratibial transplantation of tumors, Int. J. Cancer 3:765.PubMedCrossRefGoogle Scholar
  27. Goldenberg, D. M., Sharkey, R. M., and Primus, F. J., 1976, Carcinoembryonic antigen in histo-pathology: Immunoperoxidase staining of conventional tissue sections, J.Natl. Cancer Inst. 57:11PubMedGoogle Scholar
  28. Haagensen, C. D., 1972, in:The Lymphatics in Cancer (C. D. Haagensen, C. R. Feind, F. C. Herter, C. A. Slanetz, and J. A. Weinberg, eds.), pp. 14–21, Saunders, Philadelphia.Google Scholar
  29. Hagmar, B., and Ryd, W., 1978, Metastasis spread from syngeneic murine tumours: Establishment of a test protocol for comparisons between ascites tumours and their progenitors, Acta Pathol. Microbiol. Scand. Sect.A 86:231.Google Scholar
  30. Hanna, M. G., Jr., and Peters, L. C., 1978, Specific immunotherapy of established visceral microme-tastases by BCG-tumor cell vaccine alone or as an adjunct to surgery, Cancer 42:2613.PubMedCrossRefGoogle Scholar
  31. Hanna, M. G., Jr., Zbar, B., and Rapp, H. J., 1972, Histopathology of tumor regression after intralesional injection of Mycobacterium bovis. I. Tumor growth and metastasis, J. Natl. Cancer Inst. 48:1441.PubMedGoogle Scholar
  32. Herman, P. G., Kim, C.-S., de Sousa, M. A. B., and Mellins, H. Z., 1976, Microcirculation of the lymph node with metastases, Am. J. Pathol. 85:333.PubMedGoogle Scholar
  33. Hewitt, H. B., and Blake, E. R., 1975, Quantitative studies of translymphnodal passage of tumour cells naturally disseminated from a non-immunogenic murine squamous carcinoma, Br. J. Cancer 31:25.PubMedCrossRefGoogle Scholar
  34. Hewitt, H. B., and Blake, E. R., 1977, Further studies of the relationship between lymphatic dissemination and lymphnodal metastasis in non-immunogenic murine tumours, Br. J. Cancer 35:415.PubMedCrossRefGoogle Scholar
  35. Jobsis, A. C., de Vries, G. P., Anholt, R. R. H., and Sanders, G. T. B., 1978, Demonstration of the prostatic origin of metastases, Cancer 41:1788.PubMedCrossRefGoogle Scholar
  36. Kim, U., 1970, Metastasizing mammary carcinomas in rats: Their induction and study of their immunogenicity, Science 167:72.PubMedCrossRefGoogle Scholar
  37. Kim, U., Baumler, A., Carruthers, C., and Bielat, K., 1975, Immunological escape mechanisms in spontaneously metastasizing mammary tumours, Proc. Natl. Acad. Sci. USA 72:1012.PubMedCrossRefGoogle Scholar
  38. Kodama, T., Gotohda, E., Takeichi, N., Kuzumaki, N., and Kobayashi, H., 1974, Histopathology of immunologic regression of tumor metastasis in the lymph nodes, J. Natl. Cancer Inst. 52:931.PubMedGoogle Scholar
  39. Kohno, K., Yamaguchi, T., and Takahashi, T., 1979, An experimental study of the spread of tumor cells through the lymph node, Tohoku J. Exp. Med. 127:183.PubMedCrossRefGoogle Scholar
  40. Kramer, R. H., and Nicolson, G. L., 1979, Interactions of tumor cells with vascular endothelial cell monolayers: A model for metastatic invasion, Proc. Natl. Acad. Sci. USA 76:5704.PubMedCrossRefGoogle Scholar
  41. Kreider, J. W., Bartlett, G. L., and Purnell, D. M., 1976, Suitability of rat mammary adenocarcinoma 13762 as a model for BCG immunotherapy, J. Natl. Cancer inst. 56:797.PubMedGoogle Scholar
  42. Kreider, J. W., Bartlett, G. L., Purnell, D. M., and Webb, S., 1978a, Immunotherapy of an established rat mammary adenocarcinoma (13762A) with intratumor injection of Corynebacterium parvum, Cancer Res. 38:689.PubMedGoogle Scholar
  43. Kreider, J. W., Bartlett, G. L., Purnell, D. M., and Webb, S., 1978b, Destruction of regional lymph node metastases of rat mammary adenocarcinoma 13762A by treatment with Corynebacterium parvum, Cancer Res. 38:4522.PubMedGoogle Scholar
  44. Kreider, J. W., Bartlett, G. L., and Purnell, D. M., 1980, Immunotherapy of post operative metastases of 13762A rat mammary adenocarcinoma. Comparative effectiveness of BCG substrains and methods of preparation, Cancer 46:500.PubMedCrossRefGoogle Scholar
  45. Leak, L. V., and Burke, J. F., 1966, Fine structure of the lymphatic capillary and the adjoining connective tissue area, Am. J. Anat. 118:785.PubMedCrossRefGoogle Scholar
  46. Leak, L. V., and Burke, J. F., 1968, Ultrastructural studies on the lymphatic anchoring filaments, J. Cell Biol. 36:129.CrossRefGoogle Scholar
  47. Lee, Y.-T. N. M., 1980a, The surgeon’s approach to lymph node biopsy and dissection, in:Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 119–137, Hall, Boston.Google Scholar
  48. Lee, Y.-T. N. M., 1980b, Lymph node involvement in soft tissue and bone sarcoma, in:Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 410–433, Hall, Boston.Google Scholar
  49. Liotta, L. A., Tryggvason, K., Garbisa, S., Hart, I., Foltz, C. M., and Shafie, S., 1980, Metastatic potential correlates with enzymatic degradation of basement membrane collagen, Nature (London ) 284:67.CrossRefGoogle Scholar
  50. Ludwig, J., and Titus, J. L., 1967, Experimental tumor cell emboli in lymph nodes, Arch. Pathol. 84:304.PubMedGoogle Scholar
  51. Luncksen, C., and Strauli, P., 1975, Penetration of an ascitic reticulum cell sarcoma of the golden hamster into the body wall and through the diaphragm, Virchows Arch. B. 17:247.Google Scholar
  52. Mayerson, H. S., 1969, Three centuries of lymphatic history—An outline, Lymphology 2:143.Google Scholar
  53. Moore, J. V., and Dixon, B. , 1977, Metastasis of a transplantable mammary tumour in rats treated with cyclophosphamide and/or irradiation, Br. J. Cancer 36:221.PubMedCrossRefGoogle Scholar
  54. Nakamura, T., Mine, H., Okudaira, Y., Yaita, A., Sugimachi, K., Ueo, H., Natsuda, Y., and Inokuchi, K., 1978, Mode of lymphatic metastasis in the esophageal cancer using VX2 carcinoma in rabbits, Nippon Kyobu Geka Gakkai Zasshi 26:656.PubMedGoogle Scholar
  55. Onuigbo, W. I., 1972, Historical data on the dynamics of lymphatic metastasis, Oncology 26:505.PubMedCrossRefGoogle Scholar
  56. Palmer, P. E., and Wolfe, H. J., 1978, Immunocytochemical localization of oncodevelopmental proteins in human germ cell and hepatic tumors, J. Histochem. Cytochem. 26:523.PubMedCrossRefGoogle Scholar
  57. Palmer, P. E., Safari, H., and Wolfe, H. J., 1976, Alpha1antitrypsin and alpha-fetoprotein protein markers in endodermal sinus (yolk-sac) tumors, Am. J. Clin. Pathol. 65:575.PubMedGoogle Scholar
  58. Perez, C. A., Stewart, C. C., Palmer-Hanes, L. A., and Powers, W. E., 1973, Role of the regional lymph nodes in the cure of a murine lymphosarcoma, Cancer 32:562.PubMedCrossRefGoogle Scholar
  59. Pickren, J. W., 1961, Significance of occult metastases: A study of breast cancer, Cancer 14:1266.PubMedCrossRefGoogle Scholar
  60. Plotkin, D., 1980, Chemotherapy of lymph node metastases: Differential response, in:Lymphatic System Metastasis (L. Weiss, H. A. Gilbert, and S. C. Ballon, eds.), pp. 200–209, Hall, Boston.Google Scholar
  61. Pollard, M., and Luckert, P. H., 1975, Transplantable metastasizing prostate adenocarcinoma in rats, J. Natl. Cancer Inst. 54:643.PubMedGoogle Scholar
  62. Poste, G., and Fidler, I. J., 1980, The pathogenesis of cancer metastasis, Nature (London) 283:139.CrossRefGoogle Scholar
  63. Pullinger, B. D., and Florey, H. W., 1935, Some observations on the structure and function of lymphatics: Their behaviour in local oedema, Br. J. Exp. Pathol. 16:49.Google Scholar
  64. Rappaport, D. S., and Brown, J. M., 1979, Influence of localized preinoculation irradiation of the foot on lymphatic metastasis from a primary tumor growing in the foot, Radiat. Res. 78:108.PubMedCrossRefGoogle Scholar
  65. Roos, E., and Dingemans, K. P., 1979, Mechanisms of metastasis, Biochim. Biophys. Acta 560:135.PubMedGoogle Scholar
  66. Sato, H., 1961, Study on the role of cancer chemotherapy for prevention of lymph node metastases, Cancer Chemother. Rep. 13:33.PubMedGoogle Scholar
  67. Silberberg-Sinakin, I., and Thorbecke, F. J., 1980, The Langerhans cell, in: The Reticuloendothelial System , Vol. 1, Morphology (I. Carr and W. T. Daems, eds.), pp. 555–605, Plenum Press, New York.Google Scholar
  68. Sparks, F. C., O’Connell, T. X., Lee, Y.-T. N., and Breeding, J. H., 1974, BCG therapy given as an adjuvant to surgery: Prevention of death from metastases from mammary adenocarcinoma in rats, J. Natl. Cancer Inst. 53:1825.PubMedGoogle Scholar
  69. Stein-Werblowsky, R., 1978, On the lymphatic spread of cancer, Experientia 34:1340.PubMedCrossRefGoogle Scholar
  70. Stoker, T. A. M., 1969a, The effect of cortisone therapy and limb exercise on the dissemination of cancer via the lymphatic system, Br. J. Cancer 23:132.PubMedCrossRefGoogle Scholar
  71. Stoker, T. A. M., 1969b, The effect of cortisone therapy and limb exercise on the retention of tumour cells by the regional lymph node, Br. J. Cancer 23:136.PubMedCrossRefGoogle Scholar
  72. Takahashi, T., Mizuno, M., Fujita, Y., Ueda, S., Nishioka, B., and Majima, S., 1973, Increased concentration of anticancer agents in regional lymph nodes by fat emulsion, with special reference to chemotherapy of metastasis, Gann 64:345.PubMedGoogle Scholar
  73. Takahashi, T., Ueda, S., Kono, K., and Majima, S., 1976, Attempt at local administration of anticancer agents in the form of fat emulsion, Cancer 38:1507.PubMedCrossRefGoogle Scholar
  74. Takahashi, T., Kono, K., Yamaguchi, T., Watanabe, S., and Majima, S., 1977, Enhancement of chemotherapeutic effect on lymph node metastasis by anticancer agents in fat emulsion, Gann Monogr. Cancer Res. 20:195.Google Scholar
  75. Takazawa, H., and Shimizu, S., 1976, An experimental model for lymphatic metastasis in rats, Gann 67:403.PubMedGoogle Scholar
  76. Tarin, D. (ed.), 1972, Morphologic studies on the mechanisms of carcinogenesis, in:Tissue Interactions in Carcinogenesis , pp. 227–289, Academic Press, New York.Google Scholar
  77. Tjernberg, B., and Zajicek, J., 1965, Cannulation of lymphatics leaving cancerous nodes in studies on tumor spread, Acta Cytol. 9:197Google Scholar
  78. Tsukagoshi, S.., Inouye, T., and Sakurai, Y., 1973, Chemotherapy of lymph node metastasis by thigh and footpad inoculation of mouse leukemia L-1210 cells, Gann 64:189.PubMedGoogle Scholar
  79. Turner, G. A., and Weiss, L., 1980, Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells, Int. J. Cancer 26:247.PubMedCrossRefGoogle Scholar
  80. van de Velde, C. J. H., and Carr, I., 1977, Lymphatic invasion and metastasis, Experientia 33:837.PubMedCrossRefGoogle Scholar
  81. van de Velde, C. J. H., van Putten, L. M., and Zwaveling, A., 1977a, A new metastasizing mammary carcinoma model in mice: Model characteristics and applications, Eur. J. Cancer 13:555.Google Scholar
  82. van de Velde, C. J. H., van Putten, L. M., and Zwaveling, A., 1977b, Effects of regional lympha-denectomy and adjuvant chemotherapy on metastasis and survival in rodent tumour models, Eur. J. Cancer 13:883.PubMedGoogle Scholar
  83. van de Velde, C. J. H., Meyer, C. J. L. M., Cornelisse, C. J., van der Velde, E. A., van Putten, L. M., and Zwaveling, A., 1978, A morphometric analysis of lymph node responses to tumors of different immunogenicity, Cancer Res. 38:661.PubMedGoogle Scholar
  84. van Putten, L. M., Kram, L. K. J., van Dierendonck, H. H. C, Smink, T., and Fuzy, M., 1975, Enhancement by drugs of metastatic lung nodule formation after intravenous tumour cell injection, Int. J. Cancer 15:588.PubMedCrossRefGoogle Scholar
  85. Weiss, L., 1980, Metastasis: Differences between cancer cells in primary and secondary tumors, in: Pathology Annual, 1980 , Vol. 10 (H. L. Ioachim, ed.), pp. 51–81, Raven Press, New York.Google Scholar
  86. Weiss, L., and Holmes, J. C, 1980, Some effects of tumor necrosis on components of active cell movement, in:Proteinases and Tumor Invasion (P. Strauli, A. J. Barrett, and A. Baici, eds.), pp. 151–199, Raven Press, New York.Google Scholar
  87. Weiss, L., Gilbert H. A., and Ballon, S. C. (eds.), 1980a, Lymphatic System Metastasis , Hall, Boston.Google Scholar
  88. Weiss, L., Haydock, K., Pickren, J. W., and Lane, W. W., 1980b, Organ vascularity and metastatic frequency, Am. J. Pathol. 101:101.PubMedGoogle Scholar
  89. Westby, S., McGinty, F., and Carr, I., 1976, A quantitative microscopical study of tumor cell nuclei in lymphatic metastasis using a quantimet, J. Pathol. 119:5.PubMedCrossRefGoogle Scholar
  90. Willis, R. A., 1952, The Spread of Tumors in the Human Body , Butterworths, London.Google Scholar
  91. Yoffey, J. M., and Courtice, F. C, 1970, Lymphatics, Lymph and the Lymphomyeloid Complex , Academic Press, New York.Google Scholar
  92. Zbar, B., Bernstein, I. D., Bartlett, G. L., Hanna, M. G., Jr., and Rapp, H. J., 1972, Immunotherapy of cancer: Regression of intradermal tumors and prevention of growth of lymph node metastases after intralesional injection of living Mycobacterium bovis, J. Natl. Cancer Inst. 49:119.PubMedGoogle Scholar
  93. Zbar, B., Smith, H. G., and Bast, R. C, Jr., 1976, Immunologic eradication of lymph-node metastases, in:BCG in Cancer Immunotherapy (G. Lamoureaux, R. Turcotte, and V. Portelance, eds.), pp. 361–366, Grune & Stratton, New York.Google Scholar
  94. Zbar, B., Hunter, J. T., Rapp, H. J., and Canti, G. F., 1978, Immunotherapy of bilateral lymph node metastases in guinea pigs by intralesional or paralesional injection of Mycobacterium bovis (BCG), J. Natl. Cancer Inst. 60:1163.PubMedGoogle Scholar
  95. Zeidman, I., 1965, Fate of circulating tumor cells. III. Comparison of metastatic growth produced by tumor cell emboli in veins and lymphatics, Cancer Res. 25:324.PubMedGoogle Scholar
  96. Zeidman, I., and Buss, J. M., 1954, Experimental studies on the spread of cancer in the lymphatic system. I. Effectiveness of the lymph node as a barrier to the passage of embolic tumor cells, Cancer Res. 14:403.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Ian Carr
    • 1
  • Jean Carr
    • 2
  1. 1.Department of PathologyUniversity of Manitoba, and St. Boniface HospitalWinnipegCanada
  2. 2.Department of PhysiologyUniversity of SaskatchewanSaskatoonCanada

Personalised recommendations