Micrometastasis

Micrometastasis is defined as a microscopic deposit of malignant cells, smaller than 2-3 mm, that are segregated spatially from the primary tumour [193]. The fate of micrometastases is uncertain; the majority of them are probably destined for destruction or dormancy, and only a small percentage of circulating tumour cells survive and initiate a metastatic focus [1].

The fundamental characteristic of micrometastasis is the absence of a specific blood supply. Micrometastases are thus dependent on passive diffusion for oxygen and nutrient supply. Experimental studies have shown that without new blood vessel formation (neo-angiogenesis), the growth of tumour cells is limited to 2-3 mm and may remain dormant for months or even years. During dormancy, the proliferation is balanced by an equivalent rate of cell death by apoptosis. After induction of neoangiogenesis, apoptosis is significantly reduced, but the proliferation rate remains unchanged, and the growth of the clinically overt metastasis can occur because of the increased survival of the tumour cells [158].

Micrometastases can be detected anywhere in the body, but most frequently in the lymph nodes, in the surgical margins, in the blood and in bone marrow [112]. Their detection can be accomplished by serial sectioning light microscopy, immunohistochemistry, and/ or molecular analysis [35, 112, 130, 146].

The clinical and prognostic implication of microme-tastases is still uncertain. It has been suggested that residual micrometastatic tumour cells may increase the risk of tumour recurrence, thus resulting in failure of the primary treatment. Furthermore, the presence of tumour cells in the blood and/or bone marrow may be an indicator of a generalised disease with possible dissemination to many organs [163]. Several studies have demonstrated that lymph node micrometastases are associated with a high risk of recurrence and poor survival in patients with carcinoma of the breast, oesophagus, stomach, colon and lung [163], but few studies have been focused on the clinical significance of micrometastases in SCCs of the head and neck [112, 379].

It appears that the detection of micrometastases is a promising approach that might enable us to identify candidates for adjuvant treatment strategies [163]. However, further studies are needed to define more precisely the clinical implication of micrometastases, as well as the most appropriate method for their detection.

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