Abstract
The process of lymph node metastasis was studied in an animal model (termed O-1N) that was successfully established using a metastatic tumor to the submandibular lymph node from a chemically induced squamous cell carcinoma of the hamster tongue. The model has been maintained by serial transplantation of metastatic tumors into the buccal pouch. Lymphovascular invasion of transplanted O-1N in the tongue was examined in serial histologic sections. Lymphatic vessels were distinguished from blood vessels by Masson's trichrome stain for vascular smooth muscle, BSA-I lectin binding for vascular endothelium, and laminin and type IV collagen immunostaining for the vascular basement membrane. Transplanted tumors enlarged progressively with invasion of surrounding tissues of the tongue and resulted in lymph node metastasis in all animals with successful takes. Local growth of the tumors in the tongue was accompanied by stromal proliferation with abundant dilated lymphatic vessels which contained clusters of tumor cells. On serial sections, the carcinoma cell clusters in lymphatics in the close proximity of tumor nests were in continuity with adjacent tumor nests, whereas such continuity was not recognized in those occurring apart from tumor nests. The formation of isolated carcinoma cell clusters resulting from disintegration of elongated processes of tumor nests with invasion of lymphatics and subsequent transport in lymphatics and deposition in lymph nodes in clusters were well demonstrated in other serial sections. The key step of lymph node metastasis therefore appears to be direct invasion of lymphatic vessels by tumor cells, similar to their invasion of adjacent tissues but different from the way that blood cells escape through vessel walls. Proliferation of lymphatics around tumor nests and transport of tumor cells in clusters would also contribute to the production of metastatic deposits in lymph nodes.
Similar content being viewed by others
References
Constantinidis P, Hewitt D and Harkey M, 1989, Vessel invasion by tumour cells.Virchows Archiv [A],415, 355–46.
Tobai S, Kawaguchi T, Asahina S and Nakamura K, 1980, Some findings on the intravasation of Yoshida sarcoma cells in the omentum.Gann,71, 578–9.
Carr I, McGinty F and Norris P, 1976, The fine structure of neoplastic invasion: invasion of liver, skeletal muscle and lymphatic vessels by the Rd/3 tumor.J Pathol,118, 91–9.
Carr J, Carr I, Dreher B and Betts K, 1980, Lymphatic metastasis: Invasion of lymphatic vessels and efflux of tumor cells in the afferent popliteal lymph as seen in the Walker rat carcinoma.J Pathol,132, 287–305.
Carr I, Carr J and Dreher B, 1981, Lymphatic metastasis of mammary adenocarcinoma.Invasion Metastasis,1, 34–53.
Carr I, 1983, Lymphatic metastasis.Cancer Metastasis Rev,2, 307–17.
Ohtake K, Shingaki S and Nakajima T, 1990, A model for the study of lymph node metastasis from oral carcinoma by serial transplantation of metastatic tumor in hamsters.Oral Surg Oral Med Oral Pathol,69, 701–7.
Fujita K, Kalu T, Sasaki M and Onoe T, 1973, Experimental production of lingual carcinomas in hamsters by local application of 9,10-dimethyl-1,2-benzanthracene.J Dent Res,52, 327–32.
Cheng J, Saku T, Okabe H and Furthmayr H, 1992, Basement membranes in adenoid cystic carcinoma.Cancer,69, 2631–40.
Saku T and Okabe H, 1989, Differential lectin-binding in normal and precancerous epithelium and squamous cell carcinoma of the oral mucosa.J Oral Pathol Med,18, 438–45.
Arthur KCL, Ronald AD and Hubert JW, 1986, Intramammary lymphatic invasion in breast carcinomas.Am J Surg Pathol,10, 589–94.
Gabbert HE, Meier S, Gerharz CD and Hommel G, 1991, Incidence and prognostic significance of vascular invasion in 529 gastric-cancer patients.Int J Cancer,49, 203–7.
Kato S and Miyauchi R, 1989, Enzyme-histochemical visualization of lymphatic capillaries in the mouse tongue: light and electron microscopic study.Okajimas Folia Anat Jpn,65, 391–404.
Ohtsuki Y, Kubo H and Magari S, 1990, Immunohistochemical differentiated between lymphatic vessels and blood vessels-use of anti-basement membrane antibodies and anti-factor VIII-related antigen.Arch Histol Cytol,53, 95–105.
Hultberg BM and Svanholm H, 1989, Immunohistochemical differentiation between lymphangiographically verified lymphatic vessels and blood vessels.Virchows Archiv [A],414, 209–215.
Little D, Said JW, Siegel R, Fealy M and Fishbein MC, 1986, Endothelial cell markers in vascular neoplasm: an immunohistochemical study comparing factor VIII related antigen, blood group specific antigens, 6-keto-PGF 1 alpha, andUlex europaeus I lectin.J Pathol,149, 89–95.
Svanholm H, Nielsen K and Hauge P, 1984, Factor VIII-related antigen and lymphatic collecting vessels.Virchows Arch [A],404, 223–8.
Barsky SH, Baker A, Siegal GP, Togo S and Liotta LA, 1983, Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries.Am J Surg Pathol,7, 667–77.
Harmainen HA, Karttunen T, Sarkkinen MA, Dammert K and Risteli L, 1988, Laminin and type IV collagen in different histological stages of Kaposi's sarcoma and other vascular lesions of blood vessel or lymphatic vessel origin.Am J Surg Pathol,12, 469–76.
Arthur KCL, Ronald AD, Mark LS, Gerald JH and Hubert JW, 1990, Prognostic significance of peritumor lymphatic and blood vessel invasion in node-negative carcinoma of the breast.J Clin Oncol,8, 1457–65.
Fallowfield ME and Cook MG, 1990, Lymphatics in primary cutaneous melanoma.Am J Surg Pathol,14, 370–74.
Larsen MP, Steinberg GD, Brendler CB and Epstein JI, 1990, Use ofUlex europaeus agglutinin I (UEA-I) to distinguish vascular and pseudovascular invasion in transitional cell carcinoma of bladder with lamina propria invasion.Mod Pathol,3, 83–8.
Ordoneza NG, Brooks T, Thompson S and Batsakis JG, 1987, Use ofUlex europaeus agglutininI in the identification of lymphatic and blood vessel invasion in previously stained microscopic slides.Am J Surg Pathol,11, 543–50.
Alroy J, Goyal V and Skutelsky E, 1987, Lectin histochemistry of mammalian endothelium.Histochemistry,86, 603–7.
Roussel F and Dalion J, 1988, Lectins as markers of endothelial cells: comparative study between human and animal.Lab Anim,22, 135–40.
Carr I, Watson P and Pettigrew NM, 1989, Mechanisms of invasion and lymphatic penetration in human colorectal cancer.Clin Exp Metastasis,7, 507–16.
Sugino T, 1989, An experimental study on hematogenous lung metastasis of spontaneous mammary adenocarcinoma in C3H mice.Fukushima Igaku Zasshi,39, 255–75 (in Japanese).
Ohtake K, Shingaki S and Nakajima T, 1993, Histological study on the metastatic process in the experimental model of lymph node metastasis.Oral Surg Oral Med Oral Pathol,75, 472–8.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshizawa, M., Shingaki, S., Nakajima, T. et al. Histopathological study of lymphatic invasion in squamous cell carcinoma (O-1N) with high potential of lymph node metastasis. Clin Exp Metast 12, 347–356 (1994). https://doi.org/10.1007/BF01755878
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01755878