Regional Lymph Node Metastases

Experimental studies have shown that metastatic progression is initiated by local invasion: select tumour cells are released from the tumour where they gain entry to the lymphatic system or circulation, mainly via the production of tumour-derived proteolytic enzymes and angiogenic factors [220].

Cancer cells commonly invade thin-walled lymphatic vessels, capillaries and veins (Fig. 1.21), whereas thicker-walled arterioles and arteries are relatively resistant. The appearance of vascular invasion should not be considered synonymous with metastasis, because most of the tumour cells that enter the lymphatic system and circulation are destroyed [1]. However, the penetration of tumour cells in the lymphatic and blood vessels is associated with a high probability of regional lymph node and distant metastases. Furthermore, it allows the tumour to spread beyond the apparent margins. The presence of vascular invasion is therefore associated with an increased incidence of recurrence and poor survival [383].

In perineural invasion, the tumour cells enter the perineural space and spread both proximally and distally along the nerve fibre. Even though a perineural spread of more than 2 cm is unusual, the travelling of tumour cells up to 12 cm away from the primary tumour site along the perineural space has been described [101, 370].

Patients with perineural invasion may be asymptomatic, or may experience pain and paresthesia [40]. It appears that perineural invasion is a poor prognostic sign,

Squamous cell carcinomas of the head and neck have a high tendency to metastasise to the regional lymph nodes. The localisation and frequency of the lymph node metastases depend upon the site and size of the primary tumour. Large metastases can be detected clinically by examination or using ultrasound or radiographic methods. Smaller metastases evade clinical detection, but are detected by light microscopy [111].

Routine analysis of neck dissection specimens is usually limited to the examination of a few sections of each node stained by haematoxylin-eosin. During such routine analysis, small metastases can easily be missed. It has been demonstrated that with more sensitive techniques, nodal metastases can be detected in 8-20% of patients in whom metastases had not been found during routine histologic examination [11, 146, 147]. The most commonly used sensitive techniques for the detection of small metastases are serial section light microscopy, im-munohisto chemistry and molecular analysis [130, 273, 307, 379].

The prognostic significance of lymph node metastases has been extensively studied. Metastasis in the lymph nodes is the most significant adverse prognostic factor in head and neck SCCs. The 5-year survival is decreased by approximately 50% in patients with lymph node metastases compared with patients without nodal involvement [10, 25, 320]. The number and size of positive nodes, their level in the neck and the presence of extracapsular spread are the most important prognostic parameters for nodal status [10, 85, 109, 230].

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