Pathology of the Head and Neck

14 N. Gale · N. Zidar1a b cFig. 1.13. a Well-differentiated squamous cell carcinoma. b Moderatelydifferentiated squamous cell carcinoma. c Poorly differentiatedsquamous cell carcinomaoropharynx, larynx and hypopharynx. Less frequently,it arises in the nasopharynx, nasal cavities and paranasalsinuses. The predilection sites in the oral cavityare the lateral tongue and floor of the mouth. Inthe oropharynx, the most commonly involved sites arethe base of the tongue and the tonsils. In the larynx,there are geographic differences in the topographicdistribution, the glottis being the most frequent locationin some countries, and the supraglottis in others[20, 117].1.3.2.1 AetiologySmoking and alcohol abuse are the greatest risk factorsfor the development of SCCs of the head and neck. Muchattention has been paid to the possible role of viral infection,particularly the Epstein-Barr virus (EBV), andthe human papillomavirus (HPV), in the pathogenesisof the head and neck carcinoma.The EBV is aetiopathogenetically strongly related tonasopharyngeal carcinomas [265], and to rare cases oflymphoepithelial carcinoma of the salivary glands [153,160]. HPV has been aetiologically linked to SCCs of thetonsil [97, 214]. Apart from tonsillar SCC and nasopharyngealSCC, it appears that EBV and HPV play little, ifany, role in the pathogenesis of SCCs in other locationsin the head and neck [93, 153, 227, 392].1.3.2.2 Pathologic FeaturesThe macroscopic appearance of invasive SCCs is variable,and includes flat lesions with a well-defined, raisededge, polypoid exophytic and papillary lesions, as wellas endophytic infiltrative lesions. The surface of the tumouris frequently ulcerated.Microscopically, SCCs are characterised by an invasivegrowth and evidence of squamous differentiation.Invasive growth is manifested by interruption of thebasement membrane and the growth of islands, cords,or single (dyscohesive) tumour cells in the subepithelialstroma; large tumours may invade deeper structures,i.e. muscle, cartilage and bone. Perineural invasion andinvasion of lymphatic and blood vessels may be presentand are reliable proof of invasive cancer. Squamousdifferentiation is demonstrated by intercellular bridgesand/or keratinisation, with keratin pearl formation.Immunohistochemically, SCCs express epithelialmarkers, such as cytokeratins and epithelial membraneantigen (EMA). The patterns of expression of cytokeratinsubtypes are related to the degree of SCC differentiationand to the degree of keratinisation [229].The pattern of cytokeratin expression in low-gradeSCCs is similar to that observed in non-neoplastic squamousepithelium, and is characterised by medium andhigh molecular weight cytokeratins, and the lack of expressionof the low molecular weight cytokeratins. HighgradeSCCs tend to lose the expression of medium andhigh molecular weight cytokeratins and express low molecularweight cytokeratins [229].Of the various cytokeratin subtypes, cytokeratins 8,18 and 19, recognised by the antibody CAM5.2, couldbe used as an indicator of malignant transformation.In a study by Mallofré et al., 40% of SCCs were positivefor CAM5.2, but it was never positive in non-neoplasticsquamous epithelium [229]. In poorly differentiatedSCCs, expression of vimentin may appear [367].