Typical carcinoid tumor of the larynx occurring with otalgia: a case report

Neuroendocrine neoplasms of the larynx comprise a rare group of tumors that have a controversial history with regard to their classification. The World Health Organization categorizes these tumors as typical carcinoids, atypical carcinoids, small-cell neuroendocrine carcinomas, and paragangliomas. Atypical carcinoids and small-cell neuroendocrine carcinomas are the more common. Only 13 cases of typical carcinoid have been reported. Local excision is sufficient for typical carcinoids and paragangliomas, but atypical carcinoids require neck dissection because of their tendency to metastasize. Small-cell neuroendocrine carcinomas are not cured by local excision, and these patients have the worst prognosis (5-year survival: 5%); their treatment is limited to chemo- and radiotherapy. Because of these variations in tumor behavior and treatment, it is essential that otolaryngologists and pathologists to be able to correctly identify the specific type of tumor in order to optimize patient treatment and survival. We report a case of typical carcinoid and review the pertinent literature on this subject.     

Immunohistochemical and fine structural characterization of primary carcinoid tumors of the larynx

Carcinoid tumors belong to the group of neuroendocrine tumors of epithelial origin, i.e., neuroendocrine carcinomas. These neoplasms usually occur in the gastrointestinal tract or bronchial system but are very rare neoplasms in the larynx. Since carcinoid tumors in this latter site may appear to be undifferentiated by light microscopy, they may possibly be misinterpreted and their neuroendocrine characteristics may remain unrecognized. Using immunohistochemical methods, three carcinoid tumors were studied and showed positive immunostaining for markers of epithelial origin (cytokeratins, epithelial membrane antigen, carcino-embryonic antigen) and, in particular, for markers of neuroendocrine differentiation (chromogranin, synaptophysin, neuron-specific enolase). All tumors expressed calcitonin-, serotonin- and adrenocorticotropic-hormone-like immunoreactivity. In contrast, three poorly differentiated squamous cell carcinomas showed positive immunostaining for epithelial markers but did not show any immunoreactivity with markers of endocrine characteristics. Fine structurally, carcinoid tumor cells contained neurosecretory-type granules scattered throughout the cytoplasm. The present study demonstrated that (1) carcinoid tumors of the larynx possess distinct immunohistochemical characteristics that allow a clear classification, (2) it is advisable to use a battery of primary antibodies rather than rely on specificity and sensitivity of a single marker to establish diagnosis and (3) the fine structural demonstration of neurosecretory-type granules serves as a reliable adjunct to diagnosis.The results were presented in part at the 65th annual meeting of the German Society for Otorhinolaryngology-Head and Neck Surgery (Deutsche Gesellschaft für Hals-Nasen-Ohrenheilkunde, Kopf- and Halschirurgie), Chemnitz, 14–18 May 1994     

Neuroendocrine neoplasms of the larynx

Neuroendocrine neoplasms of the larynx are a rare group of tumors that include carcinoid tumor, atypical carcinoid tumor, and small cell carcinoma. These neoplasms pose interesting diagnostic, prognostic, and therapeutic dilemmas, and they are, as a whole, aggressive tumors with a tendency for local and distant spread. The authors of this study examined six new cases of laryngeal neuroendocrine neoplasms. One case manifested itself as a primary atypical carcinoid tumor and caused a “carcinoid syndrome.” The remaining five cases were small cell carcinomas of the larynx. Histologic, immunocytochemical, DNA flow cytometric, and p⁵³ studies were performed on all cases. The expression of neuron-specific enolase and chromogranin were the most useful markers in this group of tumors. Overexpression of p⁵³ protein was present in the majority of cases, including the atypical carcinoid tumor. The implications of these studies for diagnosis, classification, and treatment are discussed.     

Carcinoid (neuroendocrine) tumor of the arytenoid.

We reviewed three cases of neuroendocrine carcinoid tumors of the larynx, located on the arytenoid cartilage, treated between 1962 and 1985 at the Laennec Hospital, University of Paris (France) V. Staging was performed according to the 1979 American Joint Committee for Cancer Staging Classification. None of the lesions were associated with symptoms of the carcinoid syndrome. Local and nodal recurrences, distant metastasis, and survival were analyzed. Among the 112 reported carcinoid (neuroendocrine) tumors of the larynx, arytenoid location represented 28.6% (32/112) of the cases. A review of these 32 patients was performed to analyze the problems associated with that location.     

Atypical carcinoid (moderately differentiated neuroendocrine carcinoma) of the uvula

Carcinoid (neuroendocrine) tumors of the head and neck rarely occur outside the larynx and, until now, none has been reported in the oral cavity. We describe what we believe is the first reported case of an atypical carcinoid tumor, or any other type of neuroendocrine carcinoma, of the uvula.     

发生于耳鼻咽喉部的原发性神经内分泌癌4例

目的：探讨发生于耳鼻咽喉部的原发性神经内分泌癌的的病理、临床特性及治疗方法；方法：喉非典型类癌1例，行会厌切除术；鼻咽部非典型类癌1例。行放疗；中耳类癌1例，行右中耳探查及乳突根治术；右鼻腔小细胞神经内分泌癌1例，行鼻右侧切开肿瘤切除术及放疗。结果：喉非典型类癌及鼻咽部非典型类癌患者分别于5年和1年后死亡；中耳类癌患者随访3年右耳术腔干洁；右鼻腔小细胞神经内分泌癌随访2年未见复发。结论：发生于耳鼻咽喉部的原发性神经内分泌癌可分为类癌、非典型类癌、小细胞神经内分泌癌。类癌为低度恶性。小细胞神经内分泌癌为高度恶性，非典型类癌介于二者之间。治疗以手术切除为主．     

Neuroendocrine tumors of the larynx (NETL)

CASUISTRY: The case of a patient with atypical carcinoid of the larynx is reported and literature about neuroendocrine tumors of the larynx (NETL) is reviewed. BACKGROUND: Especially terminology, histological differentiation, diagnostics and therapy are discussed. CONCLUSIONS: Neuroendocrine tumors are rare and untypically located in the larynx. In spite of this they should to be known as an important differential diagnosis of a laryngeal neoplasia, because of possible malign or highly malign course. The typical localisation of neuroendocrine tumors (NET) are the gastrointestinal tract and the lung, but the clinical course differs from the one of laryngeal manifestation. This means diagnostics and therapy have to be adapted to this special disease. That's why it is important to explore the identity of these tumors scientifically. This is difficult because of the low rate of patients with this disease. The message of this report is the conclusion of the established and appeal for publications of new cases of NETL.     

Laryngeal paraganglioma: an updated critical review

Laryngeal paragangliomas are rare submucosal lesions that arise from paraganglion cells located in the false vocal fold and subglottic larynx. To date, 76 recognized cases have been reported in the world literature. Symptoms arise when the lesions become large enough to impair function. Supraglottic paragangliomas cause hoarseness and deglutition disorders, whereas subglottic tumors become symptomatic when they obstruct the airway. Evaluation of these tumors includes obtaining a complete history. Familial paragangliomas and hypertension should be sought but are rarely, if ever, associated with laryngeal paragangliomas. MRI can detect these lesions and permit characterization of the vascularity of the lesion. Adding 111In pentetreotide scanning can distinguish neuroendocrine tumors from other submucosal laryngeal lesions, making the preoperative diagnosis clearer and obviating the need for biopsy. The biggest dilemma regarding laryngeal paragangliomas is making the correct pathologic distinction between paraganglioma, typical carcinoid, atypical carcinoid and medullary thyroid cancer. Immunohistochemical markers, supplementing standard histopathologic evaluation, can distinguish paragangliomas from the aforementioned tumors. This distinction is critical as the prognosis for treated paragangliomas is excellent compared to that for other neuroendocrine neoplasms. Almost all alleged malignant paragangliomas of the larynx are in reality atypical carcinoid tumors that have been misdiagnosed. Treatment should always comprise excision. Thyrotomy has the best chance of achieving a sustained cure without damaging phonation or deglutition. Laser excision has been used successfully but there is no great experience with this modality. Surgery is preferable to radiation for paragangliomas in all locations but especially so in the larynx, due to issues such as swelling, airway protection and destruction of cartilage. With increased clinical suspicion and the use of modern imaging techniques, laryngeal paragangliomas should be routinely diagnosed and treated without loss of laryngeal functions.     

Laser excision of a typical carcinoid tumor of the larynx: a case report

Neuroendocrine carcinomas of the larynx include a range of rare tumors which have variable biologic behavior, affecting treatment and prognosis. Among these, typical carcinoid tumors are the least common type. Prognosis of typical carcinoid tumor is better than atypical carcinoid tumor and small cell carcinoma of the larynx. Conservation surgery is the preferred treatment modality. Transoral CO2 laser surgery can be a good alternative for appropriate cases because of the functional results and less morbidity. In this article, a 71-year-old female presented with complaints of feeling a mass during swallowing. Fiberoptic examination of the larynx revealed a mass located on the right aryepiglottic fold and biopsy revealed the tumor as a typical carcinoid tumor. We describe CO2 laser excision of a typical carcinoid tumor of the larynx in this case report.     

喉神经内分泌癌的研究进展

喉神经内分泌癌是一种罕见的起源于上皮型神经内分泌细胞的喉恶性肿瘤,根据分化程度和细胞类型分为4种组织学亚型:典型类癌、非典型类癌、小细胞神经内分泌癌和大细胞神经内分泌癌。不同肿瘤亚型差异很大,由于发病率过低致使这些差异的正确描述一直受到阻碍。因报道过少的病例或无法收集足够的样本量,文献中常常存在相互矛盾的结果,很难形成共同的认知。综述近期的文献资料,就喉神经内分泌癌的临床行为、特点、诊断、治疗及预后等方面进行文献复习,提高临床医生对该病的认识,优化诊治方案。     

Neuroendocrine carcinoma of the larynx

Neoplasms of the larynx showing neuroendocrine differentiation are uncommon, with less than 100 previously reported cases. These tumors encompass subcategories that have been designated heretofore as "malignant carcinoid" and "oat cell carcinoma" and have been associated with ectopic production of neuropeptides and biogenic amines. We report a case of neuroendocrine carcinoma that arose in the epiglottis in an elderly man, metastasized widely, and was responsible for death. Immunohistochemical studies showed the presence of serotonin, calcitonin, ACTH, met-enkephalin, chromogranin, and neuron-specific enolase within tumor cells, although clinical endocrinopathy was absent. This case is used as a focus for discussion of the spectrum of neuroendocrine tumors of the head and neck, including recommended treatment approaches for such neoplasms.     

Neuroendocrine neoplasms of the larynx importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma

Findings in the present study have confirmed that the diagnosis of neuroendocrine tumors of the larynx (NETL) requires that a panel of neuroendocrine markers and electron microscopy be performed. This means that the clinician must be aware of the clinical presentations of such patients and should send fresh biopsy specimens to the clinical laboratory for optimal tissue studies. As shown in this study, the possibility of misdiagnosis of an atypical carcinoid tumor (ACT) is rather high. In establishing a diagnosis, a part of the material should be fixed for conventional histology, a part for immunohistochemistry and a part for electron microscopy. The correct diagnosis of NETL is obviously of great importance for subsequent treatment and prognosis. Patients with the diagnosis of ACT of the larynx require surgical treatment. Our findings also show that small-cell neuroendocrine carcinomas of the larynx should be considered to be a disseminated disease at initial presentation. A metastatic workup is necessary, but radical surgical procedures should be avoided. The combination of radiotherapy and chemotherapy is always indicated.     

Neuroendocrine tumors of larynx.

Neuroendocrine neoplasms of the larynx have either an epithelial or a neural basis. The former are more numerous and are classified as typical or atypical carcinoids and small cell neuroendocrine carcinomas. Paraganglioma is the sole type of neural neuroendocrine neoplasm. There is a significant worsening of prognosis from typical carcinoid to small cell neuroendocrine carcinoma, with the latter having a dismal 5-year survival rate regardless of therapy. Paragangliomas are the most benign of laryngeal neuroendocrine neoplasms, but their clinical behavior may not be predictable on the basis of their histologic appearance.     

Primary carcinoid tumor of the frontal sinus: A case report

Carcinoid tumors are rare, indolent, neuroendocrine tumors that are most commonly found in the gastrointestinal tract and lungs. They occasionally develop in the head and neck, either as a primary tumor or, more commonly, as a metastasis. The most common sites of head and neck carcinoids are the larynx and middle ear. Only a few cases of carcinoid in the nasal cavity and paranasal sinuses have been reported. We describe a case of primary typical carcinoid of the frontal sinus in a 61-year-old man, and we review the clinical, imaging, surgical, and histochemical findings in this case. The patient was treated with endoscopic resection. A subsequent workup for metastatic and occult primary disease was negative, confirming that the frontal sinus was the primary source. At follow-up 12 months postoperatively, the patient remained without disease. To the best of our knowledge, this is the first report of a primary typical carcinoid tumor originating in the frontal sinus.     

Primary carcinoid tumor of the parotid gland: A case report and review of the literature

Salivary gland tumors account for 3 to 6% of all head and neck neoplasms in adults. Some 70 to 85% of these lesions are found in the parotid. Carcinoid tumors, which represent a distinct and relatively uncommon subset of neuroendocrine tumors, are most commonly found in the gastrointestinal tract, although in rare cases they are known to occur in extragastrointestinal locations, including the larynx, middle ear and pancreas. Malignancies of the parotid gland are uncommon (approximately 25% of parotid neoplasms), and to the best of our knowledge, a primary carcinoid tumor of the parotid has not been previously described in the literature. Reports of parotid carcinoid tumors during the past 30 years have described the presence of nonparotid primary carcinoid tumors (usually gastrointestinal) that had been diagnosed and treated several years prior to the presentation of the parotid lesion. Under such circumstances, the parotid lesion may be assumed to have been a metastatic rather than a primary carcinoid. This report documents what we believe is the first case of a primary carcinoid tumor of the parotid gland. We detail the clinical, surgical, radiologic, immunologic, and histochemical findings associated with its diagnosis, and we describe our management of this case. Although a primary carcinoid in this location is exquisitely rare, knowledge of such lesions is important because their management is substantially different from that of other parotid tumors. In particular, it is important to differentiate them from metastatic tumors from other sites.     

Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance

Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.     

Treatment of neuroendocrine neoplasms of the larynx.

The best treatment for carcinoid tumor is surgical excision. The mainstay of treatment for atypical carcinoid tumor is wide surgical resection, often with elective neck dissection. Although it is not effective in the management of paragangliomas and carcinoid tumors, primary radiation therapy with adjuvant chemotherapy is the treatment of choice for small cell neuroendocrine carcinoma of the larynx. Management of laryngeal paraganglioma is surgical and may often be accomplished by partial laryngectomy. Most tumors are supraglottic and may be resected via modified lateral pharyngotomy. Preoperative angiography and embolization are occasionally useful.     

A study of moderately differentiated neuroendocrine carcinomas of the larynx and an examination of non-neoplastic larynx tissue for neuroendocrine cells

OBJECTIVES/HYPOTHESIS: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. STUDY DESIGN: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. METHODS: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. RESULTS: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. CONCLUSIONS: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC.     

Pathology and biologic behavior of laryngeal carcinoid

A case of carcinoid of the larynx was reported and other 8 cases collected from the literature were analysed. The average age of the patients was 66.8 years, which was 5-10 years older than that of patients with squamous carcinoma of the larynx. Carcinoid is rarely present in the larynx. The route of the spread is mainly through the blood stream rather than local infiltration. The prognosis for patients with carcinoid of the larynx is more favorable than that of squamous carcinoma of the larynx, but more serious than that of carcinoid of the lung and intestine. The 5-year survival rate was less than 50%. Histochemical study revealed that the carcinoid of the larynx was one of the foregut type, and might arise from neuroendocrine cells of the ectoderm.     

Primary carcinoid tumour of the larynx

Carcinoid neoplasms, although rare, have to be considered in the differential diagnosis of neoplasms of the larynx. The total number of cases reviewed and listed in the present article is 47. The gross appearance of carcinoid tumours is not characteristic and does not differ from that of other malignant neoplasms of the larynx. Under the light microscope various types can be distinguished, which are described and illustrated in this review article. Available material of five previously published cases and of one new case have been re-examined under the electron microscope and by modern histochemical and immunohistochemical methods. The ultrastructural presence of neurosecretory granules and of argyrophilia by the Grimelius technique were uniformly positive, together with monoclonal antibodies for somatostatin and keratin. These special methods offer a reliable basis for the diagnosis of neuroendocrine neoplasms to which carcinoid tumours belong. The treatment of carcinoid neoplasms of the larynx is surgical.