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

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.

Thyroid transcription factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid

“…Although the morphologic findings of these tumors have not varied, the nomenclature of laryngeal neuroendocrine neoplasms has changed since the time that they were first recognized. [2][3][4]6,17,18 In 1993, the World Health Organization (WHO) subdivided laryngeal neuroendocrine tumors into carcinoid, atypical carcinoid and small cell carcinoma. 17 More recently, it has been suggested 2 that the following nomenclature would more accurately represent morphologic and biologic differences between laryngeal neuroendocrine neoplasms: well-differentiated neuroendocrine carcinoma (typical carcinoid), moderately differentiated neuroendocrine carcinoma (atypical carcinoid), poorly differentiated neuroendocrine carcinoma-small cell type and poorly differentiated neuroendocrine carcinoma-large cell type.…”

“…Additionally, immunohistochemistry has not proven to be useful in making this distinction since both tumors are immunoreactive with keratins, neuroendocrine markers, CEA and calcitonin. 1,4,6 Currently, the only known objective discriminator between moderately differentiated neuroendocrine carcinoma of the larynx and medullary carcinoma of the thyroid is serum calcitonin, which should be elevated in medullary carcinomas of the thyroid and within normal limits in moderately differentiated neuroendocrine carcinomas of the larynx. However, there are rare exceptions as three out of over 300 reported cases of moderately differentiated neuroendocrine carcinoma of the larynx in the literature were reportedly associated with an elevated level of calcitonin.…”

“…Currently, serum calcitonin is the only objective means for distinguishing primary moderately differentiated neuroendocrine carcinoma of the larynx from metastatic medullary carcinoma, as calcitonin immunohistochemistry is reportedly positive in both tumors. [3][4][5][6] Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcription factor that is selectively expressed in developing respiratory epithelium, thyroid and diencephelon. 7,8 Immunohistochemical studies have shown that TTF-1 is expressed in a subset of lung and most thyroid neoplasms, including pulmonary neuroendocrine tumors and medullary carcinoma of the thyroid.…”

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

“…This is consistent with the finding that surgery alone may be adequate for the very rare carcinoid and carcinoid-like tumors of the head and neck, as it is for carcinoid and carcinoid-like tumors at other body sites. 24 The extreme rarity of head and neck carcinoids (fewer than 20 patients are reported in the published literature 6 ) makes it impossible to make any different treatment recommendation for those arising in head and neck sites different from those arising at any other body site.…”

“…The NSNECs are rare enough that they are represented in the literature primarily by sporadic case reports. 6 We contend that the differences in tumor types and treatment strategies for sinonasal and nonsinonasal sites justify a separate analysis. We reviewed our institutional experience in patients with NSNEC to determine the optimal management parameters for this disease.…”