Pathology of the Head and Neck

26 N. Gale · N. Zidar1associated with an increased risk of local recurrence, regionallymph node metastases and decreased survival[101, 233, 333, 383].1.5.3 Regional Lymph Node MetastasesFig. 1.21. Tumour emboli in a lymph vessel and vein1.5.1 Invasion of Lymphaticand Blood VesselsExperimental studies have shown that metastatic progressionis initiated by local invasion: select tumourcells are released from the tumour where they gain entryto the lymphatic system or circulation, mainly via theproduction of tumour-derived proteolytic enzymes andangiogenic factors [220].Cancer cells commonly invade thin-walled lymphaticvessels, capillaries and veins (Fig. 1.21), whereas thickerwalledarterioles and arteries are relatively resistant. Theappearance of vascular invasion should not be consideredsynonymous with metastasis, because most of thetumour cells that enter the lymphatic system and circulationare destroyed [1]. However, the penetration of tumourcells in the lymphatic and blood vessels is associatedwith a high probability of regional lymph nodeand distant metastases. Furthermore, it allows the tumourto spread beyond the apparent margins. The presenceof vascular invasion is therefore associated withan increased incidence of recurrence and poor survival[383].1.5.2 Perineural InvasionIn perineural invasion, the tumour cells enter the perineuralspace and spread both proximally and distallyalong the nerve fibre. Even though a perineural spreadof more than 2 cm is unusual, the travelling of tumourcells up to 12 cm away from the primary tumour sitealong the perineural space has been described [101,370].Patients with perineural invasion may be asymptomatic,or may experience pain and paresthesia [40]. It appearsthat perineural invasion is a poor prognostic sign,Squamous cell carcinomas of the head and neck havea high tendency to metastasise to the regional lymphnodes. The localisation and frequency of the lymph nodemetastases depend upon the site and size of the primarytumour. Large metastases can be detected clinically byexamination or using ultrasound or radiographic methods.Smaller metastases evade clinical detection, but aredetected by light microscopy [111].Routine analysis of neck dissection specimens is usuallylimited to the examination of a few sections of eachnode stained by haematoxylin-eosin. During such routineanalysis, small metastases can easily be missed. Ithas been demonstrated that with more sensitive techniques,nodal metastases can be detected in 8–20% ofpatients in whom metastases had not been found duringroutine histologic examination [11, 146, 147]. The mostcommonly used sensitive techniques for the detection ofsmall metastases are serial section light microscopy, immunohistochemistryand molecular analysis [130, 273,307, 379].The prognostic significance of lymph node metastaseshas been extensively studied. Metastasis in thelymph nodes is the most significant adverse prognosticfactor in head and neck SCCs. The 5-year survival is decreasedby approximately 50% in patients with lymphnode metastases compared with patients without nodalinvolvement [10, 25, 320]. The number and size of positivenodes, their level in the neck and the presence ofextracapsular spread are the most important prognosticparameters for nodal status [10, 85, 109, 230].1.5.3.1 Extracapsular Spreadin Lymph Node MetastasesCancer cells initially lodge in the marginal sinus, andthen extend throughout the lymph node. Metastasesmay be confined to the lymph node, or may penetrate thecapsule and infiltrate the perinodal tissue; this patternof growth has been referred to as extracapsular spread(ECS). Extracapsular spread is further divided into macroscopicand microscopic ECS [62]; macroscopic ECS isevident to the naked eye during the laboratory dissectionof the surgical specimen and is later confirmed byhistological assessment. It usually involves not only theperinodal fibro-adipose tissue, but also the surroundingstructures. Microscopic ECS is only evident on histologicexamination and is usually limited to the adjacentperinodal fibro-adipose tissue.