Well-differentiated neuroendocrine carcinoma (WD-NEC) is the least common type of laryngeal NEC. In a critical review of the world literature, El-Naggar and Batsakis found only 12 well-documented cases of laryn-geal WD-NEC . Since then, a few more cases have been described in the English-language literature [67, 191, 242, 326, 341, 391].
Well-differentiated NEC occurs predominantly in males, the average age is 58 years, and the majority (83%) are located in the supraglottis . They present clinically with dyspnoea, hoarseness and/or sore throat.
Grossly, laryngeal WD-NEC is typically a submu-cosal nodule or a polypoid lesion measuring up to 2 cm in diameter. Microscopically, like WD-NEC elsewhere in the body, they are composed of small uniform cells growing in islands, ribbons and cords, occasionally forming gland-like structures. Mucin may occasionally be present. The nuclei are round, with finely dispersed chromatin and inconspicuous nucleoli; the cytoplasm is scant, clear or eosinophilic. Mitoses are sparse or absent, and there is no necrosis or cellular pleomorphism.
Immunohistochemically, laryngeal WD-NEC expresses markers of neuroendocrine differentiation (such as chromogranin, synaptophysin, neuron-specific eno-lase, Leu-7), and markers of epithelial differentiation (such as cytokeratins and epithelial membrane antigen) . Electron microscopy reveals dense-core neurosecretory granules [91, 106].
Differential diagnosis includes moderately differentiated NEC, paraganglioma, and adenocarcinoma, and is discussed in the next section.
The treatment of choice is complete but conservative surgical excision. Neck dissection is not indicated. Radiotherapy and chemotherapy have not proven effective [106, 248].
The prognosis is favourable, although metastases to the lymph node, liver, bones and skin have been reported in one-third of patients. Only one patient has died of the disease . These data suggest the more aggressive behaviour of laryngeal WD-NEC compared with bronchial WD-NEC, but the number of patients is too small to draw any conclusions .
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