Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

Chapter 3 “Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space” of the World Health Organization (WHO) Blue Book 2017 “Classification of Head and Neck Tumours” shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial—mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.