Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Precursors and Problematic Variants

In the head and neck region, the most common lesion encountered by the otolaryngologist and the pathologist relates to alterations of the surface squamous epithelium. This review will focus on the squamous epithelial alterations of the upper aerodigestive tract (UADT), including premalignant lesions and squamous cell carcinoma (SCC). Premalignant squamous epithelial lesions of the UADT present diagnostic challenges in that the majority of dysplastic epithelial changes are of the keratinizing type, to which the continuum of mild to moderate to severe dysplasia to invasive carcinoma that characterizes the nonkeratinizing dysplasias does not consistently apply. This results in problems in the histologic grading of these changes and raises questions about what constitutes a diagnosis of severe dysplasia. In this context, the justification for using the designation carcinoma in situ relative to keratinizing dysplasia becomes questionable. I will attempt to address these issues focusing on the spectrum of squamous dysplasias (nonkeratinizing and keratinizing), as well as on the justification of using the term carcinoma in situ for the keratinizing dysplasias of the UADT. The section on head and neck SCC (HNSCC) will include the diagnostic criteria for recognizing early or microinvasive SCC, pitfalls in differentiating benign lesions that histologically simulate invasive SCC, and the prognostic factors related to HNSCC. There are numerous variants of HNSCC ( Table 1 ). Some of these variants include papillary SCC, verrucous carcinoma (VC), spindle cell squamous carcinoma, basaloid SCC, nasopharyngeal carcinoma, and adenoid SCC. The diagnostic criteria and diagnostic problems associated with these specific subtypes of HNSCC will be discussed. TABLE 1 Head and Neck Squamous Cell Carcinoma (SCC) and Variants Full size table The last section of this manuscript includes a brief discussion on genetic aspects of HNSCC, specifically directed at the concept of field cancerization and clonality of multifocal SCC, as well as etiologic agents associated with HNSCC. Finally, emerging diagnostic and prognostic modalities that are currently being used for HNSCC are presented.