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A review of neuroendocrine neoplasms of the larynx: update on diagnosis and treatment

  • Alfio Ferlito (a1), Leon Barnes (a2), Alessandra Rinaldo (a3), Douglas R. Gnepp (a4) and Christopher M. Milroy (a5)...

Abstract

Neuroendocrine neoplasms of the larynx have been divided into those of epithelial or neural origin. The latter consist of paragangliomas while the epithelial origin group can be divided into the typical and atypical carcinoids and small cell neuroendocrine carcinomata, the latter consisting of the oat cell type, the intermediate cell type and the combined cell type. There are now over 500 cases of neuroendocrine neoplasms of the larynx in the literature.

The diagnosis is primarily based on light microscopy, and, in some instances, it may be supported by special histochemical studies. It should be confirmed by immunocytochemical and/or ultrastructural investigation. The different biological behaviour of neuroendocrine neoplasms of the larynx makes a specific diagnosis of paramount importance, since treatment depends on diagnostic accuracy.

Typical carcinoid is an extremely rare lesion. It is treated preferably by conservative surgery; elective neck dissection is not necessary because of the lack of lymph node metastases at diagnosis. Chemotherapy and/or radiotherapy have not been effective in the limited number of patients treated thus far. Prognosis is excellent with cure following surgery.

Atypical carcinoid is the most frequent non-squamous carcinoma of the larynx. The mainstay of treatment is surgery. Elective neck dissection should be performed because of the high likelihood of cervical lymph node metastases. Primary radiation therapy with adjuvant chemotherapy is not indicated. The survival rate is 48 per cent at five years and 30 per cent at 10 years.

Although the larynx is one of its most common extrapulmonary sites, small cell neuroendocrine carcinoma is still a rare tumour. Surgical results for this tumour have been disappointing and is reserved for cases of local relapse with no evidence of metastasis. Chemotherapy and radiotherapy currently appear to offer the least disabling and most effective forms of therapy. The two- and five-year survival rates are 16 per cent and five per cent, respectively.

Paraneoplastic syndromes have occasionally been reported in association with carcinoid tumours (typical and atypical) and small cell neuroendocrine carcinoma. There have been also rare reports of an elevated neuropeptide serum level.

Paraganglioma is the only laryngeal neuroendocrine neoplasm with a female preponderance (3:1). Confusion with atypical carcinoid has led to incorrect diagnosis and inappropriate classification schemes, erroneously suggesting that laryngeal paraganglioma has the potential for aggressive behaviour. Conservative surgery represents the treatment of choice; elective neck dissection is not necessary, and the prognosis is excellent.

Copyright

Corresponding author

Address for correspondence: Alfio Ferlito, M.D., Department of Otolaryngology – Head and Neck Surgery, University of Udine, Policlinico Citta di Udine, Viale Venezia 410, 33100 Udine, Italy. Fax: 39-432-532179 e-mail: clorl@dsc.uniud.it

References

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Barnes, L. (1991) Paraganglioma of the larynx. A critical review of the literature. ORL; Journal of Oto-Rhino- Laryngology and its Related Specialties 53: 220234.
Barnes, L., Ferlito, A., Wenig, B. M. (1997) Laryngeal paragangliomas. A review and report of a single case. (Letter to the Editor) Journal of Laryngology and Otology 111: 197198.
Baugh, R. F., Wolf, G. T., Lloyd, R. V., McClatchey, K. D., Evans, D. A. (1987) Carcinoid (neuroendocrine carcinoma) of the larynx. Annals of Otology, Rhinology and Laryngology 96: 315321.
Bishop, J. W., Osamura, R. Y., Tsutsumi, Y. (1985) Multiple hormone production in an oat cell carcinoma of the larynx. Acta Pathologica Japonica 35: 915923.
Cefis, F., Cattaneo, M., Carnevale Ricci, P. M., Frigerio, B., Usellini, L., Capella, C. (1983) Primary polypeptide hormones and muein-producing malignant carcinoid of the larynx. Ultrastructural Pathology 5: 4553.
Dieler, R., Dammrich, J. (1995) Immunohistochemical and fine structural characterization of primary carcinoid tumours of the larynx. European Archives of Oto-Rhino- Laryngology 252: 229235.
Duvall, E., Johnston, A., McLay, K., Piris, J. (1983) Carcinoid tumour of the larynx. A report of two cases. Journal of Laryngology and Otology 97: 10731080.
El-Naggar, A. K. (1992) Laryngeal neuroendocrine carcinoma. Victims of semantics. Archives of Pathology and Laboratory Medicine 116: 237238.
El-Naggar, A. K., Batsakis, J. G. (1991) Carcinoid tumor of the larynx. A critical review of the literature. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 188193.
El-Naggar, A. K., Batsakis, J. G., Vassilopoulou-Sellin, R., Ordonez, N. G., Luna, M. A. (1991) Medullary (thyroid) carcinoma-like carcinoids of the larynx. Journal of Laryngology and Otology 105: 683686.
Ereño, C., Lopez, J. I., Sanchez, J. M. (1997) Atypical carcinoid of larynx: presentation with scalp metastases. Journal of Laryngology and Otology 111: 8991.
Ferlito, A., Barnes, L., Wenig, B. M. (1994) Identification, classification, treatment, and prognosis of laryngeal paraganglioma. Review of the literature and eight new cases. Annals of Otology, Rhinology and Laryngology 103: 525536.
Ferlito, A., Friedmann, I. (1989) Review of neuroendocrine carcinomas of the larynx. Annals of Otology, Rhinology and Laryngology 98: 780790.
Ferlito, A., Friedmann, I. (1991) Contribution of immunohistochemistry in the diagnosis of neuroendocrine neoplasms of the larynx. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 235244.
Ferlito, A., Friedmann, I. (1993) Neuroendocrine neoplasms. In Neoplasms of the Larynx. (Ferlito, A., ed.), Churchill Livingstone, Edinburgh, pp 169205.
Ferlito, A., Friedmann, I., Goldman, N. C. (1988) Primary carcinoid tumour of the larynx. ORL; Journal of Oto- Rhino-Laryngology and its Related Specialties 50: 129149.
Ferlito, A., Milroy, C. M., Barnes, L. (1996) Neuroendocrine neoplasms. In Surgical Pathology of Laryngeal Neoplasms. (Ferlito, A., ed.), Chapman and Hall, London, pp 173193.
Ferlito, A., Milroy, C. M., Wenig, B. M., Barnes, L., Silver, C. E. (1995) Laryngeal paraganglioma versus atypical carcinoid tumor. Annals of Otology, Rhinology and Laryngology 104: 7883.
Ferlito, A., Rosai, J. (1991) Terminology and classification of neuroendocrine neoplasms of the larynx. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 185187.
Gnepp, D. R. (1991) Small cell neuroendocrine carcinoma of the larynx. A critical review of the literature. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 210219.
Googe, P. B., Ferry, J. A., Bhan, A. K., Dickersin, G. R., Pilch, B. Z., Goodman, M. (1988) A comparison of paraganglioma, carcinoid tumor, and small-cell carcinoma of the larynx. Archives of Pathology and Laboratory Medicine 112: 809815.
Gripp, F. M., Risse, E. K. J., Leverstein, H., Snow, G. B., Meijer, C. J. L. M. (1995) Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma. European Archives of Oto-Rhino-Laryngology 252: 280286.
Hartley, C., Birzgalis, A. R., Lyons, T. J., Farrington, W. T. (1996) Neuroendocrine carcinoma of the larynx. Journal of the Royal College of Surgeons of Edinburgh 41: 333335.
Johnson, T. L., Zarbo, R. J., Lloyd, R. V., Crissman, J. D. (1988) Paragangliomas of the head and neck: immunohistochemical neuroendocrine and intermediate filament typing. Modern Pathology 1: 216223.
Kau, R., Arnold, W. (1996) Somatostatin receptor scintigraphy and therapy of neuroendocrine (APUD) tumors of the head and neck. Acta Oto-Laryngologica 116: 345349.
Kim, H. -J., Hwang, E. G. (1997) Small cell carcinoma of the larynx: imaging findings. Auris, Nasus, Larynx 24: 423427.
Laccourreye, O., Brasnu, D., Carnot, F., Fichaux, P., Laccourreye, H. (1991) Carcinoid (neuroendocrine) tumor of the arytenoid. Archives of Otolaryngology-Head and Neck Surgery 117: 13951399.
Lack, E. E. (1997) Tumours of the adrenal gland and extra-adrenal paraganglia. In Atlas of Tumor Pathology, 3rd series. Fasc 19. Armed Forces Institute of Pathology, Washington DC, pp 369374.
Lippi, L., Porzio, P. (1985) II carcinoide laringeo: revisione bibliografica e presentazione di un caso. Rivista di Otorinolaringoiatria, Audiologia e Foniatria 5: 137140.
Logue, J. P., Banerjee, S. S., Slevin, N. J., Vasanthan, S. (1991) Neuroendocrine carcinomas of the larynx. Journal of Laryngology and Otology 105: 10311035.
Luna, M. A. (1996) Salivary gland neoplasms. In Surgical Pathology of Laryngeal Neoplasms. (Ferlito, A., ed.), Chapman & Hall, London, pp 257294.
McCluggage, W. G., Bharucha, H., Cameron, C. H. S., Toner, P. G. (1994) Amphicrine carcinoma of the larynx. Histopathology 24: 182185.
McCluggage, W. G., Cameron, C. H. S., Arthur, K., Toner, P. G. (1997) Atypical carcinoid tumor of the larynx: an immunohistochemical, ultrastructural, and flow cytometric analysis. Ultrastructural Pathology 21: 431438.
Medina, J. E., Moran, M., Goepfert, H. (1984) Oat cell carcinoma of the larynx and Eaton-Lambert syndrome. Archives of Otolaryngology 110: 123126.
Milroy, C. M., Ferlito, A. (1995) Immunohistochemical markers in the diagnosis of neuroendocrine neoplasms of the head and neck. Annals of Otology, Rhinology and Laryngology 104: 413418.
Milroy, C. M., Robinson, P. J., Grant, H. R. (1989) Primary composite squamous cell carcinoma and large cell neuroendocrine carcinoma of the hypopharynx. Journal of Laryngology and Otology 103: 10931096.
Moisa, I. I., Silver, C. E. (1991) Treatment of neuroendocrine neoplasms of the larynx. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 259264.
Morales, C., Tomas Bezos, J., Alvarez-Quinones Sanz, M., Garcia Mantilla, J., Carrera, F. (1996) Carcinoma neuroendocrino de laringe productor de calcitonina: tumor carcinoide atipico. Acta Otorrinolaringologica Espanola 47: 333335.
Myers, T. J., Kessimian, N. (1995) Small cell carcinoma of the larynx and ectopic antidiuretic hormone secretion. Otolaryngology- Head and Neck Surgery 113: 301304.
Olofsson, J., van Nostrand, A. W. P. (1972) Anaplastic small cell carcinoma of larynx. Case report Annals of Otology, Rhinology and Laryngology 81: 284287.
Orrell, J. M., Hales, S. A. (1992) Paragangliomas of the cauda equina have a distinctive cytokeratin immunophenotype. Histopathology 21: 479481.
Overholt, S. M., Donovan, D. T., Schwartz, M. R., Laucirica, R., Green, L. K., Alford, B. R. (1995) Neuroendocrine neoplasms of the larynx. Laryngoscope 105: 789794.
Özünlü, A., Dündar, A., Satar, B., Günhan, Ö. (1996) Laryngeal paraganglioma. A review and report of a single case. Journal of Laryngology and Otology 110: 519526.
Patterson, S. D., Yarington, C. T. Jr. (1987) Carcinoid tumor of the larynx: the role of conservative therapy. Annals of Otology, Rhinology and Laryngology 96: 1214.
Peterson, K. L., Fu, Y. S., Calcaterra, T. (1997) Subglottic paraganglioma. Head and Neck 19: 5456.
Robinson, S., Hains, D., Whyte, A. (1997) Paraganglioma of the larynx. Australian Journal of Oto-Laryngology 2: 494496.
Said, J. W., Vimadalal, S., Nash, G., Shintaku, I. P., Heusser, R. C., Sassoon, A. F., Lloyd, R. V. (1985) Immunoreactive neuron-specific enolase, bombesin and chromogranin as markers for neuroendocrine lung tumours. Human Pathology 16: 236240.
Salim, S. A., Milroy, C., Rode, J., Corrin, B., Hamid, Q. (1993) Immunocytochemical characterization of neuroendocrine tumours of the larynx. Histopathology 23: 6973.
Schmidt, U., Metz, K. A., Schrader, M., Leder, L. D. (1994) Well-differentiated (oncocytoid) neuroendocrine carcinoma of the larynx with multiple skin metastases: a brief report. Journal of Laryngology and Otology 108: 272274.
Schol, D. J., Mooi, W. J., van der Gugten, A. A., Wagenaar, S. S., Hilgers, J. (1988) Monoclonal antibody 123c3, identifying small cell lung carcinoma phenotype in lung tumours, recognizes mainly, but not exclusively, endocrine and neuron-supporting normal tissues. International Journal of Cancer (Suppl 2): 3440.
Smets, G., Warson, F., Dehou, M. F., Storme, G., Sacrè, R., van Belle, S., Somers, G., Gepts, W., Klöppel, G. (1990) Metastasizing neuroendocrine carcinoma of the larynx with calcitonin and somatostatin secretion and CEA production, resembling medullary thyroid carcinoma. Virchows Archiv (A) 416:539543.
Snyderman, C., Johnson, J. T., Barnes, L. (1986) Carcinoid tumor of the larynx: case report and review of the world literature. Otolaryngology - Head and Neck Surgery 95: 158164.
Stanley, R. J., DeSanto, L. W., Weiland, L. H. (1986) Oncocytic and oncocytoid carcinoid tumors (well-differentiated neuroendocrine carcinomas) of the larynx. Archives of Otolaryngology - Head and Neck Surgery 112: 529535.
Steinberg, D. M., Kashima, H. K. (1998) Atypical carcinoid tumor (moderately differentiated neuroendocrine carcinoma) of the larynx. Archives of Otolaryngology - Head and Neck Surgery 124: 219, 221222.
Sweeney, E. C., McDonnell, L., O'Brien, C. (1981) Medullary carcinoma of the thyroid presenting as tumours of the pharynx and larynx. Histopathology 5: 263275.
Takeuchi, K., Nishii, S., Jin, C. S., Ukai, K., Sakakura, Y. (1989) Anaplastic small cell carcinoma of the larynx. Auris, Nasus, Larynx 16: 127132.
Trotoux, J., Glickmanas, M., Sterkers, O., Trousset, M., Pinel, J. (1979) Syndrome de Schwartz-Bartter: révélateur d'un cancer laryngé sous-glottique à petites cellules. Annales d'Oto-Laryngologie et de Chirurgie Cervico-Faciale 96: 349358.
Watters, G. W. R., Molyneux, A. J. (1995) Atypical carcinoid tumour of the larynx. Journal of Laryngology and Otology 109: 455458.
Wenig, B. M. (1993) Atlas of Head and Neck Pathology. Saunders, Philadelphia, PA, pp 227266.
Wenig, B. M., Gnepp, D. R. (1989) The spectrum of neuroendocrine carcinoma of the larynx. Seminars in Diagnostic Pathology 6: 329350.
Wenig, B. M., Hyams, V. J., Heffner, D. K. (1988) Moderately differentiated neuroendocrine carcinomas of the larynx: a clinicopathologic study of 54 cases. Cancer 62: 26582676.
Woodruff, J. M., Huvos, A. G., Erlandson, R. A., Shah, J. P., Gerold, F. P. (1985) Neuroendocrine carcinomas of the larynx. A study of two types, one of which mimics thyroid medullary carcinoma. American Journal of Surgical Pathology 9: 771790.
Woodruff, J. M., Senie, R. T. (1991) Atypical carcinoid tumor of the larynx. A critical review of the literature. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 53: 194209.
World Health Organization. Histological Typing of Tumours of the Upper Respiratory Tract and Ear. (1991) Springer-Verlag, Berlin.
Zambruno, G., Bertazzoni, M. G., Botticelli, A., Manca, V., Giannetti, A. (1989) Carcinome neuroendocrine du larynx avec métastases cutanées. Annales de Dermatologie et de Venereologie 116: 855858.
Barnes, L. (1993) Paragangliomas of the larynx. (Letter to the Editor). Journal of Laryngology and Otology 107: 664666.
Blanchard, C. L., Saunders, W. H. (1955) Chemodectoma of the larynx: case report. Archives of Otolaryngology 61: 472474.
Blok, P. H. H. M., Manni, J. J., van den Broek, P., van Haelst, U. J. G. M., Sloof, J. L. (1985) Carcinoid of the larynx: a report of three cases and a review of the literature. Laryngoscope 95: 715719.
Doglioni, C., Ferlito, A., Chiamenti, C., Viale, G., Rosai, J. (1990) Laryngeal carcinoma showing multidirectional epithelial, neuroendocrine and sarcomatous differentiation. ORL; Journal of Oto-Rhino-Laryngology and its Related Specialties 52: 316326.
El-Silimy, O., Harvy, L. (1992) A clinico-pathological classification of laryngeal paraganglioma. Journal of Laryngology and Otology 106: 635639.
Ferlito, A. (1974) Oat cell carcinoma of the larynx. Annals of Otology, Rhinology and Laryngology 83: 254256.
Ferlito, A. (1986) Diagnosis and treatment of small cell carcinoma of the larynx: a critical review. Annals of Otology, Rhinology and Laryngology 95: 590600.
Ferlito, A., Barnes, L., Wenig, B. M. (1995) Identification, classification, treatment, and prognosis of laryngeal paraganglioma. Review of the literature and eight new cases. (Letter to the Editor). Annals of Otology, Rhinology and Laryngology 104: 8485.
Ferlito, A., Caruso, G., Nicolai, P., Recher, G., Silvestri, F. (1981) Primary small cell (‘oat cell’) carcinoma of the larynx and hypopharynx. A clinico-pathological study of 8 cases with a review of the literature. ORL; Journal of Oto-Rhino- Laryngology and its Related Specialties 43: 204222.
Ferlito, A., Pesavento, G., Recher, G., Caruso, G., Dal Fior, S., Montaguti, A., Carraro, R., Name, S., Pennelli, N. (1986) Long-term survival in response to combined chemotherapy and radiotherapy in laryngeal small cell carcinoma. Auris, Nasus, Larynx 13: 113123.
Ferlito, A., Polidoro, F. (1980) Simultaneous primary oat cell carcinoma (apudoma) and squamous cell carcinoma of the hypopharynx. ORL; Journal of Oto-Rhino-Laryngology and Its Related Specialties 42: 146157.
Ferlito, A., Recher, G., Caruso, G. (1985) Primary combined small cell carcinoma of the larynx. American Journal of Otolaryngology 6: 302308.
Gehanno, P., Lallemant, Y., Groussard, O., Blanchet, F., Veber, F., Guedon, C., Rame, J. A. (1980) Apudomes en O.R.L. à propos de 6 observations (dont 1 chémodectome et 1 carcinoide du larynx); critique du concept d'apudome. Journal Francois d'Oto-Rhino-Laryngologie, Audiophonologie, Chirurgie Maxillo-Faciale 29: 718.
Giddins, N. A., Kennedy, T. L., Vrabec, D. P. (1987) Primary small cell carcinoma of the larynx: analysis of treatment. Journal of Otolaryngology 16: 157165.
Gnepp, D. R., Ferlito, A., Hyams, V. (1983) Primary anaplastic small cell (oat cell) carcinoma of the larynx. Review of the literature and report of 18 cases. Cancer 51: 17311745.
Govaerts, P. J., van den Broek, P., Corstens, F. H. M., Peters, H. M. (1992) Clinical oncology: Case presentations from oncology centres - 2. Carcinoid of the larynx. European Journal of Cancer 28A: 17551758.
Insabato, L., De Rosa, G., Terracciano, L. M., Lupoli, G., Montedoro, D., Ravetto, C. (1993) A calcitonin-producing neuroendocrine tumor of the larynx. A case report. Tumori 79: 227230.
Kumai, M., Arakawa, T., Nakane, T., Shinohara, H., Uchida, S., Yanai, O., Ando, M. (1996) Serum serotonin elevated carcinoid tumor of the larynx. Larynx Japan 8: 5355.
Laudadio, P. (1971) Chemodectoma (paraganglioma non cromaffine) del glomo laringeo superiore. Otorinolaringologia Italiana 39: 1931.
Markel, S. F., Magielski, J. E., Beals, T. F. (1980) Carcinoid tumor of the larynx. Archives of Otolaryngology 106: 777778.
Milroy, C. M. (1993) Paragangliomas of the larynx. (Letter to the Editor). Journal of Laryngology and Otology 107: 664666.
Milroy, C. M., Rode, J., Moss, E. (1991) Laryngeal paragangliomas and neuroendocrine carcinomas. Histopathology 18: 201209.
Pesce, C., Tobia-Galleli, F., Toncini, C. (1984) APUD cells of the larynx. Acta Oto-Laryngologica 98: 158162.
Rüfenacht, H., Mihatsch, M. J., Jundt, K., Gächter, A., Tanner, K., Heitz, PhU. (1985) Gastric epithelioid leiomyomas, pulmonary chondroma, non-functioning metastasizing extra-adrenal paraganglioma and myxoma: a variant of Carney's triad. Report of a patient. Klinische Wochenschrift 63: 282284.
Vilde, F., Arkwright, S., Paoli, C., Perichon, I., Le Charpentier, Y., Le Bodic, M. F. (1996) Carcinome neuroendocrine laryngé avec sécrétion de calcitonine: cancer primitif ou métastase d'un cancer médullaire de la thyroïde? Annales de Pathologie 16: 104107.
Yu, Y. C., Miyazaki, J., Shin, T. (1966) Neuroendocrine cells in the cat laryngeal epithelium. European Archives of Oto- Rhino-Laryngology 253: 287293.

Keywords

A review of neuroendocrine neoplasms of the larynx: update on diagnosis and treatment

  • Alfio Ferlito (a1), Leon Barnes (a2), Alessandra Rinaldo (a3), Douglas R. Gnepp (a4) and Christopher M. Milroy (a5)...

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