Pathology of the Head and Neck

Larynx and Hypopharynx Chapter 7 221Fig. 7.13. Moderately differentiated neuroendocrine carcinomaof the larynx. a Islands of closely packed small cells with hyperabchromatic nuclei beneath the surface squamous cell epithelium. bImmunohistochemical expression of CD56 in tumour cellstients with MD-NEC have an elevated level of the serumcalcitonin [23, 338].Grossly, it presents as a submucosal nodule or as apolypoid lesion measuring up to 4 cm in diameter (average1.6 cm), with or without surface ulceration.Microscopically, the tumour grows in rounded nests,trabeculae, cords, ribbons and glandular structures; thetumour cells are round, with round nuclei and a moderateamount of cytoplasm, which is slightly eosinophilicor occasionally oncocytic. Mucin production may bepresent [234].In contrast to WD-NEC, cellular pleomorphism, increasedmitotic activity and necroses are frequentlypresent in MD-NEC. Vascular and perineural invasionmay be present.Immunohistochemically, MD-NEC usually expressessynaptophysin, cytokeratin, and chromogranin; theymay also express CD56, calcitonin and carcinoembryonicantigens, but rarely serotonin (Figs. 7.13) [97, 234,242, 388].Differential diagnosis includes paraganglioma, adenocarcinoma,other neuroendocrine carcinomas andmedullary carcinoma of the thyroid gland.The differentiation between paraganglioma and MD-NEC is important because the former usually behaves asa benign tumour, while the latter behaves as an aggressivetumour. The correct diagnosis is usually possible with theuse of immunohistochemistry: MD-NEC expresses cytokeratinand carcinoembryonic antigen (CEA), whileparaganglioma does not. Both tumours express markersof neuroendocrine differentiation [18, 242]. Adenocarcinomacan be distinguished from carcinoid by the absenceof neuroendocrine markers. The presence of cellular pleomorphism,increased mitotic activity and necroses helpsto distinguish MD-NEC from WD-NEC.Differentiation from thyroid medullary carcinomamay be difficult, especially when dealing with cervicalmetastases, as tumour cells in both medullary carcinomaand MD-NEC express calcitonin by immunohistochemistry.The most important distinguishing featureis the different locations of the primary tumours. Additionaluseful information may be obtained by measuringthe serum level of CEA, which is elevated in metastaticmedullary carcinoma of the thyroid, and normalin MD-NEC [19]. The elevated serum level of calcitoninshould not be considered as a reliable feature of medullarycarcinoma, as it has been reported in patients withMD-NEC [92, 338].Moderately differentiated NEC is an aggressive, potentiallylethal tumour. Lymph node metastases havebeen reported in 43% of patients, cutaneous metastasesin 22% and distant metastases in 44% of patients, mostlyto the lungs, liver and bones [97, 234, 388].Surgery is the treatment of choice. Neck dissectionis also advised because of the high incidence of cervicallymph node metastases. Radiation and chemotherapyhave not been effective [248]. The 5- and 10-year survivalrates are 48 and 30% respectively [388].7.7.3.3 Poorly DifferentiatedNeuroendocrine Carcinoma(Small Cell Carcinoma)ICD-O:8041/3Poorly differentiated neuroendocrine carcinoma is theleast differentiated and the most aggressive type of NEC.It is rare, accounting for less than 0.5% of all laryngealcarcinomas. Approximately 160 cases have been describedin the literature [106, 244].