Resumen de Metastatic Tumors to the Gingiva and the Presence of Teeth as a Contributing Factor: A Literature Analysis
Background: Gingiva that is prone to inflammation may serve as a pre-metastatic niche for the attraction of circulating malignant cells. The aim of this study is to analyze cases of metastatic lesions to the gingiva compared with cases metastasizing to other oral mucosal sites. The pathogenesis of gingival metastases is discussed, with emphasis on the role of inflammation.
Methods: The English-language literature between 1916 and 2011 was searched for cases of metastatic lesions to the oral mucosa; only cases metastasizing in the oral mucosa, gingiva, and periodontium were included.
Results: Two hundred seven cases were included. The gingiva was the most common site (60.4%), followed by tongue and tonsil. The most common primary sites were lung (24.2%), kidney (13.5%), skin (10.6%), and breast (8.7%). In 27%, the oral lesion was the first sign of a malignant disease. In most cases, the lesion appeared as an exophytic mass (96%) diagnosed clinically as a reactive gingival lesion. The presence of teeth was significantly associated with the development of gingival metastases: in 108 of 125 gingival metastases, the lesion was found adjacent to teeth (P <0.001; odds ratio = 8.2). The average life expectancy after diagnosis of the metastasis was 3.7 months.
Conclusions: The gingiva is the most common site for metastases to oral soft tissues, with strong association with the presence of teeth. This finding may be related to the role of inflammation in the attraction of metastatic cells to chronically inflamed gingiva.
Metastases represent the end stage in the invasion cascade, which involves dissemination of cancer cells to distant organ sites and their subsequent adaptation to foreign tissue microenvironments (Fig. 1A). It is the process of metastasis that results in morbidity and eventual mortality, as 90% of cancer mortality is attributable to metastases.1 Advances within the past several years provide challenging insights into the cell biology and molecular aspects of the invasion/metastasis cascade that may be amenable to therapeutic targeting. Considerable evidence indicates that metastases of various cancer types to distant organs is not a random event, but is a regulated, site-specific process.2-4 This non-random process was first described by Paget5 in his �seed and soil� hypothesis: the metastatic seed grows preferentially in an organ environment that, in some way, provides a suitable soil. It is currently accepted that a successful metastasis requires a pre-metastatic niche to allow invading cancer cells to survive, colonize, and expand to form a macrometastasis.6 Figure thumbnailView larger version (50KB) Figure 1. The metastatic cascade. A) A successful metastatic colonization represents the end product of a complex series of events, including invasion through the extracellular matrix (ECM), intravasation into the blood vessels, and survival in the circulation. Circulating cancer cells that survive settle in the microvasculature of the target organ and extravasate through the vessel wall. B) The inflammatory environment present in the gingiva (circle) may provide a permissive niche for metastatic cells, allowing them to perform the essential tasks of angiogenesis, formation of supportive stroma, and immune evasion. Soluble cytokines such as interleukin-1 and tumor necrosis factor-a present in the chronically inflamed gingiva are known to facilitate metastatic progression by stimulating angiogenesis and accelerating the generation of ECM necessary for tumor stroma and also may attract or induce tumor-associated macrophages.
The oral region is not a preferred site for metastatic colonization; metastases in this location are usually the result of secondary spread from other metastatic lesions, especially those from the lungs.7,8 Differences among the various oral sites have been found mainly in the origin of the primary tumor, the clinical presentation, and between the sexes.7,8 The gingiva was found to be the preferred site among the various oral mucosal sites; most studies, however, were based on small numbers of cases or as case reports with associated literature review.7-11 Investigating the metastatic process to the gingiva is interesting, since this site is particularly prone to inflammation, and it may serve as a pre-metastatic niche (Fig. 1B). The possible role of inflammation in the distribution of metastatic deposits to the gingiva has already been raised; however, this observation has not been supported statistically.7,8 The aim of the present study is to analyze cases of metastatic lesions to the gingiva published in the English-language literature and to compare the results with cases metastasizing to other oral mucosal sites, with emphasis on the role of inflammation in the pathogenesis.
