Histopathological study of lymphatic invasion in squamous cell carcinoma (O-1N) with high potential of lymph node metastasis

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.

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

“…Clinical and animal epithelium-derived tumors usually invaded lymphatics and metastasized first to the RLNs. 10,[24][25][26] Physiologic and pathophysiologic studies provide further indirect evidence that tumor cells are more likely to invade peritumoral lymphatics than blood vessels. Lymphatic capillaries lack interendothelial tight junctions, pericytes, and basement membranes seen in blood vessels.…”

“…The orderly progression of common cancers through the lymphatic system to the blood stream has also been described in animal tumor models. 10,25 Intramammary lymphatic tumor emboli were strongly correlated with RLN and systemic metastasis in breast cancer patients when regular sections were stained with hematoxylin and eosin. 8 The incidence of blood vessel invasion was reported in 4.7%, while others reported this phenomenon in 71% of patients.…”

Markers for the lymphatic endothelium: In search of the holy grail?

“…Antibodies against basement membrane components such as collagen type IV, fibronectin, and laminin have therefore been suggested to be useful in distinguishing blood from lymphatic microcapillaries (Barsky et al, 1983;Erhard et al, 1996;Hultberg and Svanholm, 1989;Nerlich and Schleicher, 1991;Otsuki et al, 1990;Sauter et al, 1998;Yoshizawa et al, 1994). While some authors claim that no staining for basement membrane components is observed in lymphatics, others report weak or discontinuous staining.…”

The basement membrane-type heparan sulfate proteoglycan (perlecan) in ameloblastomas: its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells in culture

“…In regard to these pathophysiological events, they have been recently rather stressed to function as matrices on which parenchymal cells are attached and express genes that are required in their particular phase of events. Their different combination of molecules may lead to a specific direction, for instance, odontogenetic processes by an enamel protein predominant composition [29,31] as well as tumor invasion processes by laminin or type-IV collagen [11,15,34]. In contrast, little attention has been paid to another function of ECM molecules as carriers for nutrient transport, which is indispensable in such tissues with a scanty vascular supply as cartilage or enamel pulp.…”