Pathology of the Head and Neck

220 N. Gale · A. Cardesa · N. Zidar7ICD-O:8249/3It is the most frequent type of NEC in the larynx, constituting54% of all laryngeal neuroendocrine neoplasms,with approximately 300 cases described in the literature[106, 242].Similar to other types of NEC, MD-NEC is morecommon in males, with a wide age range from 20 to83 years. The majority of patients are heavy smokers. Itarises mostly in the supraglottic region. Hoarseness anddysphagia are the most common symptoms; 20–30% ofpatients also experience pain [19, 243]. MD-NEC is rarelyassociated with carcinoid syndrome [388]. Some paratelyin Chap. 1. Their recognition is important becausemost of them are true clinicopathologic entities, with animportant prognostic implication: basaloid SCC, adenosquamouscarcinoma and lymphoepithelial carcinomaare more aggressive than conventional SCC, while verrucousSCC and arguably, papillary SCC, have a betterprognosis than conventional SCC.7.7.2.5 TNM GradingFor the staging of laryngeal cancer, the TNM system(T – tumour, N – node, M – metastasis), establishedby the International Union Against Cancer (UICC) iswidely used [340]. Stage remains the most significantpredictor of survival. The size of the tumour and thepresence of regional and distant metastases are independentpredictors of survival.An important parameter ignored in the TNM systemis extracapsular spread. Several studies have shown thatthe presence of extracapsular spread in the lymph nodesis strongly associated with both regional recurrence anddistant metastases, resulting in decreased survival [71,116, 157, 344]. Some studies, on the contrary, have notconfirmed the independent prognostic significance ofextracapsular spread [225, 292].7.7.3 Neuroendocrine CarcinomaNeuroendocrine carcinomas (NEC) of the larynx areuncommon, accounting for less than 1% of laryngealtumours. NEC are divided into well-differentiated NEC(WD-NEC; carcinoid), moderately differentiated NEC(MD-NEC; atypical carcinoid), and poorly differentiatedNEC (PD-NEC; small cell carcinoma). MD-NEC isthe most common type of NEC in the larynx, followedby PD-NEC and WD-NEC [19, 92, 106].The putative cells of origin are the Kultschitzky-likeargyrophilic cells, which have been described in the humanlaryngeal mucosa, and are similar or identical tothe Kultschitzky cells in the bronchial mucosa [285,288]. Other possible cells of origin are the pluripotentstem cells of the surface or glandular epithelium.7.7.3.1 Well-DifferentiatedNeuroendocrine Carcinoma(Carcinoid)ICD-O:8240/3Well-differentiated neuroendocrine carcinoma (WD-NEC) is the least common type of laryngeal NEC. Ina critical review of the world literature, El-Naggar andBatsakis found only 12 well-documented cases of laryngealWD-NEC [91]. Since then, a few more cases havebeen described in the English-language literature [67,191, 242, 326, 341, 391].Well-differentiated NEC occurs predominantlyin males, the average age is 58 years, and the majority(83%) are located in the supraglottis [92]. They presentclinically with dyspnoea, hoarseness and/or sore throat.Grossly, laryngeal WD-NEC is typically a submucosalnodule or a polypoid lesion measuring up to2 cm in diameter. Microscopically, like WD-NEC elsewherein the body, they are composed of small uniformcells growing in islands, ribbons and cords, occasionallyforming gland-like structures. Mucin may occasionallybe present. The nuclei are round, with finelydispersed chromatin and inconspicuous nucleoli; thecytoplasm is scant, clear or eosinophilic. Mitoses aresparse or absent, and there is no necrosis or cellularpleomorphism.Immunohistochemically, laryngeal WD-NEC expressesmarkers of neuroendocrine differentiation (suchas chromogranin, synaptophysin, neuron-specific enolase,Leu-7), and markers of epithelial differentiation(such as cytokeratins and epithelial membrane antigen)[106]. Electron microscopy reveals dense-core neurosecretorygranules [91, 106].Differential diagnosis includes moderately differentiatedNEC, paraganglioma, and adenocarcinoma, and isdiscussed in the next section.The treatment of choice is complete but conservativesurgical excision. Neck dissection is not indicated. Radiotherapyand chemotherapy have not proven effective[106, 248].The prognosis is favourable, although metastases tothe lymph node, liver, bones and skin have been reportedin one-third of patients. Only one patient has died ofthe disease [91]. These data suggest the more aggressivebehaviour of laryngeal WD-NEC compared with bronchialWD-NEC, but the number of patients is too smallto draw any conclusions [19].7.7.3.2 Moderately DifferentiatedNeuroendocrine Carcinoma(Atypical Carcinoid)