Pathology of the Head and Neck

218 N. Gale · A. Cardesa · N. Zidar77.7.2 Invasive SquamousCell CarcinomaICD-O:8070/3Squamous cell carcinoma (SCC) is by far the most commonmalignant tumour of the larynx and hypopharynx,accounting for about 95–96% of all malignant tumoursat this location. The majority are conventional-typeSCC.7.7.2.1 EpidemiologySquamous cell carcinoma of the larynx and hypopharynxis the second most common respiratory cancer, afterlung cancer [54]. It accounts for 1.6–2% of all malignanttumours in men, and 0.2–0.4% in women [37,293]. Its incidence is increasing in much of the world,being slightly higher in urban than in rural areas. It isalso higher among blacks than whites [54, 299].Laryngeal and hypopharyngeal SCC occur most frequentlyin the sixth and seventh decades of life. It rarelyoccurs in children and adolescents [17, 274]. It is morecommon in men [54, 299], with a male:female ratio ofabout 5:1 worldwide [253]. The male:female ratio is decreasingin some countries, reflecting a greater incidenceamong women. The increasing incidence of laryngealcancer in women has been attributed to the increasedincidence of smoking over the last two decades[79].7.7.2.2 AetiologyCigarette smoking and alcohol consumption are thechief risk factors in laryngeal and hypopharyngealcancer, and smoking has been shown to have the greatesteffect. Epidemiological studies have shown that therelative risk of laryngeal cancer associated with cigarettesmoking is approximately 10 for all subsites of thelarynx and hypopharynx. The role of alcohol independentof that of tobacco is less striking, although plausible[38] and is demonstrated in some studies [329].Smoking and drinking combined have a multiplicativerather than additive effect [222, 223, 254, 367, 393].Avoidance of smoking and alcohol consumption couldprevent about 90% of the current incidence of laryngealcancer [101].Some other factors, such as gastro-oesophageal reflux,diet and nutritional factors [38, 98, 120, 200, 276,396] have also been related to an increased risk of laryngealcancer development, particularly in patients wholack the major risk factors [12, 122].Much attention has recently been paid to the possiblerole of infection with human papillomavirus (HPV)in the pathogenesis of laryngeal and hypopharyngealcancer, but the results are conflicting. HPV, mainly type16, has been found in 3–85% of laryngeal cancers [213].Moreover, HPV DNA has been detected in 12–25% ofindividuals with a clinically and histologically normallarynx [271, 313]. It appears, therefore, that HPV infectionplays little role, if any, in laryngeal carcinogenesis[126, 177, 211, 213].7.7.2.3 Anatomic SitesThe larynx is anatomically divided into three compartments:supraglottic, glottic and subglottic. Superiorlyand posteriorly, it is continuous with the hypopharynx.Because of this anatomic proximity, the tumours of thelarynx often extend to the hypopharynx, as well as viceversa, so that in large tumours, it is impossible to determinewhether it originates from the larynx or hypopharynx.There are geographic differences in the topographicdistribution of the laryngeal SCC [19, 301]. In France,Spain, Italy, Finland and the Netherlands, supraglotticSCC predominates, while in the USA, Canada, UK andSweden glottic SCC is more common. In Japan, SCC isapproximately equally distributed between the two sites.The rarest localisation of laryngeal cancer is the subglottis(1–5%) [19, 318].Determining the primary site of origin of laryngeal/hypopharyngeal cancer is important as it has a significantimpact on the clinical presentation, spread, behaviour,and prognosis [117, 300]. This, however is not alwayspossible, especially in large tumours.The most common location of supraglottic SCC is theepiglottis (45–55% of supraglottic cancer; Fig. 7.12a) ,followed by the false vocal cords (12–33%) and the aryepiglotticfolds (8–21%). The remaining cases arise fromthe ventricles and the arytenoids [19]. Supraglottic SCCtends to spread to oropharynx and pyriform sinus, but itrarely invades the glottis and thyroid cartilage.The most common symptoms in supraglottic cancerare: dysphagia, change in the quality of the voice, a sensationof a foreign body in the throat, haemoptysis, andodynophagia.Lymph node metastases are present in 30–40% of patients.The overall 5-year survival rate in supraglotticSCC is 65–75% [19, 301].Glottic SCC arises mostly from the anterior half of thevocal cord or from the anterior commissure (Fig. 7.12b) ;a posterior origin is rare. Because of poor lymphatic supply,glottic SCC tends to remain localised for a long period.As SCC progresses, it invades the vocal muscle resultingin the fixed vocal cord, which is an ominous clinicalsign [192]. In the late stages of the disease, it may extendto the opposite true vocal cord, to the supraglottisand subglottis; it may also extend through the thyroidcartilage and invade the soft tissue of the neck.