ATYPICAL CARCINOID TUMOUR OF THE LARYNX. A CASE REPORT. S.Squillaci (1) R.Marchione (1) C.Spairani (1) M.Bisceglia (2) Department of Pathology, Hospital of Vallecamonica, Esine (Italy) (1); Department of Pathology, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (Italy) (2).

INTRODUCTION Neuroendocrine neoplasms of the larynx have been recognized as the most usual non-squamous types of neoplasms of this area, accounting for less than 1% of all laryngeal neoplasms. The latest classification edited by WHO divides neuroendocrine neoplastic lesions of the larynx into two types: epithelial (including carcinoid tumour, atypical carcinoid tumour and small cell neuroendocrine carcinoma) and those of neural derivation (paraganglioma). Atypical carcinoid tumour (ACT) is the most common laryngeal neuroendocrine tumour with approximately 350 cases being reported in the international literature.

CASE REPORT A 68-year-old female with dysphagia and hoarseness has been subjected to laryngoscopy which revealed the presence of a neoplasm of the epiglottis, about 1.5 cm in diameter, greyish- white in colour, sessile, submucosal and with diffuse superficial telangiectasias. The patient has been submitted to biopsy and subsequent supraglottic laryngectomy.

Gross finding

HISTOLOGICAL FEATURES The histological specimens of the laryngeal excised tissue and subsequent metastases showed a proliferation of polygonal and columnar cells, with a nest and adenoid-like trabecular organisation. Tumor cells contained round to elongated moderately hyperchromic nuclei, prominent nucleoli, eosinophilic granular cytoplasm, and sparse mitoses. The surgical margins of the resection and the cartilage were free from tumour. Four lymph nodes showed metastatic deposits.

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PAS-DIASTASE This tumour has focally stained with mucin stains. PAS DIASTASE

Synapthophysin ChromograninCalcitonin Cam 5.2

CEA Immunohistochemical features At immunohistochemistry, the tumour cells did not react with TTF-1, whereas a strong diffuse positivity was found for calcitonin, NSE, chromogranin, synaptophysin and cytokeratins. A weak to moderate focal immunostaining for CEA was noted. TTF-1

At this point, a diagnosis of atypical carcinoid tumour of the larynx (ACT) was favoured. Six months after laryngectomy a suspicious lymphadenopathy was observed upon laterocervical echography, and bilateral cervical regional lymph node dissection was performed. Three years later, the patient developed multiple disseminated skin and subcutaneous metastases. After two years, she died of respiratory failure due to multiple pulmonary metastases.

Conclusions Laryngeal ACTs are lesions with a well-recognized capacity for local recurrence and metastasis, with a 5-year survival bit under 50%. The introduction of IHC has proved particularly useful in the recognition and classification of neuroendocrine tumours of the larynx, which on routine histological examination might otherwise have been diagnosed as undifferentiated carcinoma, acinic cell carcinoma, adenocarcinoma, or amelanotic malignant melanoma. The differential diagnosis of ACT must essentially be made versus other types of neuroendocrine neoplasms, with particular attention to paragangliomas. Paragangliomas may stain for chromogranin, synapthophysin, NSE, and galanin but they are negative for epithelial markers (cytokeratin, EMA, CEA).

References 1.Ferlito A., Devaney KO, Rinaldo A. Neuroendocrine neoplasms of the larynx: advances in identification, understanding, and management. Oral Oncol.2006;42: Ferlito A, Rinaldo A. The spectrum of endocrinocarcinomas of the larynx. Oral Oncol.2005;41: Squillaci S, Gal AA. Galanin immunoreactivity in a laryngeal paraganglioma: case report and literature review. Pathologica 2004;96: [in italian]. 4.Myssiorek D, Rinaldo A, Barnes L, Ferlito A. Laryngeal paraganglioma: an updated critical review. Acta Otolaryngol. 2004;124: