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.     

Terminology and classification of neuroendocrine neoplasms of the larynx.

The authors discuss the terminology and classification of all neuroendocrine neoplasms of the larynx. After a review of the relevant literature, they suggest adopting the nomenclature recently recommended by the World Health Organization: carcinoid tumor, atypical carcinoid tumor, small cell neuroendocrine carcinoma and paraganglioma. This terminology is easy to apply, clinically meaningful and biologically sound. Carcinoid tumor, atypical carcinoid tumor and small cell neuroendocrine carcinoma are of epithelial origin whereas paraganglioma is of neural type. The authors emphasize that it is inadequate to make a diagnosis of 'neuroendocrine tumor or carcinoma', without its proper qualification.     

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。     

喉神经内分泌癌九例临床病理分析

目的 总结喉神经内分泌癌患者的临床表现、治疗方法及预后.方法 回顾性分析2005年5月至2011年6月共收治9例喉神经内分泌癌患者的临床资料,男6例,女3例;年龄35～65岁,中位年龄58岁.结果 治疗方法采取单纯手术5例,手术加术后放化疗4例.2例喉典型类癌患者随访28、30个月未复发;3例喉不典型类癌患者,其中1例在随访至36个月时复发,再次手术后已随访30个月,未见局部复发及远处转移,另2例分别随访15、20个月,均未复发;3例喉小细胞神经内分泌癌患者,1例随访18个月仍存活,另2例分别于术后11及14个月死亡;喉副神经节瘤1例,随访32个月未复发.结论 喉神经内分泌癌诊断有赖于临床特点、组织病理学及免疫组化检查.本病并无统一治疗方案,不同病理亚型的治疗方法及预后不同,对恶性程度较高的亚型主张采取以手术为主的综合治疗方案.     

Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the larynx: a clinically aggressive tumor

OBJECTIVES: To evaluate the presentation, treatment, and outcome of a small series of patients with moderately differentiated neuroendocrine carcinoma (MDNC) of the larynx seen at one institution and to provide information on this uncommon laryngeal malignancy for therapeutic decision making. STUDY DESIGN: Retrospective analysis of medical records. Cases were identified from databases maintained by the medical informatics and pathology departments. METHODS: Patient, tumor, treatment, and outcome data were collected from medical records. Main outcome measures were recurrence, overall and disease-specific survival, and cause of death. RESULTS: Eleven patients (6 males; 5 females) seen between 1990 and 2003 had sufficient documentation for further evaluation. Patients presented with dysphagia, throat pain, or hoarseness, and all tumors arose in the supraglottis. Eight of 11 patients gave a history of cigarette use. Of the 10 patients treated with curative intent, 7 who recurred all died with disease. The average disease-free interval was 54 months, with a range of 2 to 101 months. The overall and disease-specific survival was 64 and 54 months, respectively. Nine patients were alive 3 years after diagnosis. No correlations with age, stage at presentation, or initial treatment modality and outcome (recurrence or survival) were found. CONCLUSIONS: Laryngeal MDNC is an aggressive malignancy with frequent regional and distant metastases. Although surgical resection is usually recommended, patients did respond to radiation and chemotherapy, suggesting a combined approach may be indicated. Aggressive initial therapy is needed because development of recurrence portends a poor outcome.     

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.     

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.     

喉及喉咽部非上皮源性恶性肿瘤

目的讨论临床罕见喉腔及喉咽部非上皮源性恶性肿瘤的临床特征、诊断及治疗。方法自１９８５～１９９６年１２年间，共诊治喉及喉咽部非上皮源性恶性肿瘤２６例，其中喉２３例，喉咽部３例；男２１例，女５例；年龄１６～６５岁。喉肉瘤１１例，髓外浆细胞瘤１例，恶性淋巴瘤９例，恶性黑色素瘤２例，喉咽部平滑肌肉瘤１例，恶性黑色素瘤２例。对２１例患者首选手术切除，并根据其不同的组织病理学特性选择放射治疗或／和化学治疗。结果经６个月～１０年随访，１２例存活４～１０年，其中喉肉瘤６例，声门上区恶性淋巴瘤２例，喉恶性黑色素瘤２例，喉咽部平滑肌肉瘤、恶性黑色素瘤各１例。结论此类肿瘤的共有特征为：①肿瘤表面粘膜多光滑；②喉腔肿瘤较少发生颈淋巴结转移；③临床及病理学诊断、组织学分级较困难，免疫组化检查有助于确诊。     

Nuclear ploidy in neuroendocrine neoplasms of the larynx.

Seventeen neuroendocrine neoplasms of the larynx were examined for DNA ploidy. Twelve tumours were atypical carcinoids, four paragangliomas and one a small cell neuroendocrine carcinoma. Seven atypical carcinoids were aneuploid, one diploid and one tetraploid, with metastasis being aneuploid. In three cases only skin metastases were available for study, which were aneuploid. The small cell neuroendocrine carcinoma was aneuploid. Two of the paragangliomas were aneuploid and two diploid. Like other sites, neuroendocrine neoplasms of the larynx have a high rate of aneuploidy. Determination of DNA ploidy did not provide useful diagnostic or prognostic information.     

喉神经内分泌肿瘤临床特征

目的：探讨喉神经内分泌肿瘤的临床表现、诊断及治疗。方法：回顾分析我科收治的3例喉神经内分泌肿瘤，其中非典型类癌2例，行根治性手术切除及颈廓清术；嗜铬细胞瘤1例，行肿瘤局部切除术。结果：非典型类癌2例，术后随访1年，情况稳定。嗜铬细胞瘤1例，术后随访11年，预后良好。结论：喉神经内分泌肿瘤是一组形态各异的病变，正确诊断有赖于临床特点、光镜、免疫组织化学检查，部分患者需行超微结构检查。不同类型的肿瘤应行不同的治疗方法。     

New treatment of subglottic stenosis due to Wegener's granulomatosis

Abstract Conclusions: The presented new endoscopic surgical technique offers a safe and successful approach for treatment of subglottic stenosis due to Wegener's granulomatosis. Objective: Subglottic stenosis is a potentially limiting and complex condition among patients with Wegener's granulomatosis. It causes various symptoms and often requires interventional therapy. The purpose of this study was to evaluate a new endoscopic submucosal technique. Methods: Altogether 13 consecutive patients with subglottic stenosis due to Wegener's granulomatosis were treated with a new endoscopic technique. The procedure was carried out endoscopically, removing the stenotic part submucosally, sealing back the raised mucosal flap, and the bare areas were soaked with mitomycin-C. Follow-up telephone interviews were carried out and hospital records were reviewed. Results: Patients included 3 males and 10 females, with an average age of 37.5 years. A total of 37 procedures were performed, with an average of 2.8 procedures per patient. There was a statistically significant reduction in the all symptoms related to the stenoses (p < 0.05). Mean follow-up period was 3.5 years (range 1.5-6.5 years). Overall success rate was 85%. Only one patient relapsed following adequate medical and surgical treatment. No perioperative mortality was recorded.     

Oncocytic lesions of the larynx

Summary Three cases of oncocytic lesions of the larynx diagnosed at the Section of Pathology, Dep. of Otolaryngology, Padua University from November 1974 until December 1980 are reported. The lesion is uncommon but not exceptional and occurs in elderly people. Problems connected with pathology and the clinico-therapeutic approach are dealt with. The pathogenesis of the lesion is also discussed, with particular stress on whether it is a true neoplasm or a process of metaplasia-hyperplasia from the ductal epithelium in connection with senile involution of the upper respiratory tract.Supported by private funds     

Contribution of immunohistochemistry in the diagnosis of neuroendocrine neoplasms of the larynx.

This chapter illustrates the use of mono- and polyclonal antibodies as diagnostic tools for neuroendocrine neoplasms of the larynx on the basis of data from the literature and the authors' personal experience. It is suggested that a panel of antibodies should be adopted, rather than to rely on the specificity and sensitivity of a single marker. It is also emphasized that immunohistochemical methods should serve not as a substitute but as a useful adjuvant in evaluating the morphological criteria of these neoplasms.     

Medical malpractice and cancer of the larynx

OBJECTIVE: To analyze the frequency, clinical characteristics, and legal outcomes of malpractice litigation initiated by patients with cancer of the larynx. STUDY DESIGN: Retrospective review of 23 jury verdict reports from 11 states. METHOD: Jury verdict reviews from 1976 to 1997 were obtained from a computerized legal database compiled from all state and federal civil court decisions. Reviews compile pertinent data on defendants, plaintiffs, verdict outcomes, indemnity payments, allegations of wrongdoing, and provide case summaries. RESULTS: Delays in diagnosis were alleged in 19 of 23 (83%) suits. Hoarseness was present in 10 of 19 (53%), a neck mass in 3 of 19 (16%), and no biopsy was taken in 11 of 19 (58%) of those delayed. Mean age was 47 years, with a peak incidence in the general population of 70 to 74 years. Laryngectomy was alleged to be a result or complication of delay in 12 of 19 (63%). Over half of the patients delayed received compensation, and over half of the defendants were in general practice. Outcome was poor with a 35% mortality and a total of 47% either dead of disease or alive with disease. Complications, incorrect diagnosis, and informed consent did not play a significant role in initiating litigation. CONCLUSIONS: The delayed diagnosis of cancer of the larynx associated with litigation is frequently seen in younger patients presenting with hoarseness or neck masses. These patients frequently have poor outcomes. Patients with symptoms of cancer of the larynx must be aggressively evaluated regardless of age. Risk management goals to prevent delays in diagnosis may help prevent subsequent litigation.     

Hemangiopericytoma of the larynx

Hemangiopericytomas are rare vascular neoplasms of the head and neck. Laryngeal involvement is even more rare, with only 9 previously reported cases in the literature. We present an unusual case of a 46 year old with a supraglottic hemangiopericytoma treated surgically. We will review the clinical features and treatment of hemangiopericytomas, as well as a review of the literature. Otolaryngologists need to be aware of this rare tumor that can be treated successfully with surgical resection. Close long-term follow up is needed since recurrence can present many years after initial treatment.     

External trauma to the larynx: classification, diagnosis, therapy

In contrast to internal trauma to the larynx caused by endolaryngeal procedures, trauma to the larynx caused by external forces is relatively rare. Nevertheless, the great variety of these external traumata warrants a thorough diagnosis and understanding of each case as well as a standardized and accepted method for classifying these injuries. These preconditions will facilitate successful therapy. At our three institutions cases of external trauma to the larynx, including the mechanisms of trauma, were reviewed and analyzed. Cases were classified according to the mechanisms and the sequelae of trauma. The three major categories were (a) external trauma due to the impact of blunt objects, (b) trauma after tearing of the neck and the larynx longitudinally, and (c) external trauma caused by sharp objects and gunshots. In the great majority of cases external trauma to the larynx was caused by blunt pressure and was most often due to strangulation in the course of (attempted) suicide or homicide. In a smaller number of cases sharp instruments caused external traumata. In patients surviving the immediate trauma a meticulous laryngological assessment is necessary. In addition to indirect laryngoscopy, we consider microlaryngoscopy as being indicated for investigating the soft tissues of the endolarynx. The status of the laryngeal skeleton can be determined more precisely via high-resolution computed tomography and ultrasound. Early diagnosis and appropriate therapy have a significant impact on the patient’s condition later, especially as regards scar formation, ease of breathing, and voice quality. Received: 16 August 1999 / Accepted: 19 May 2000     

The anterior commissure of the larynx

This study is based on a very large series of histological sections of non-tumour-bearing larynges, most of them in the horizontal plane. Six hundred sections in one larynx were performed to show the constitution of the anterior region of the larynx at all levels. Although the same tissues are present (fibres, glands and vessels) in almost the entire extent of the anterior segment of the larynx, there is a small zone immediately above the vocal cords with neither glands nor vessels. The authors designate this zone as ‘plane O'which separates the anterior commissure from the thyro-epiglottic ligament. It is not possible to separate the anterior commissure from the most anterior portion of the subglottis, because the glands and vessels are in continuity. There are 2 regions of the anterior part of the larynx: a supraglottic (vestibulo-epiglottic) and a glottic-subglottic to which the anterior commissure belongs.     

Postintubation granuloma of the anterior subglottic larynx

We present an unusual case of a granuloma in the subglottic laryngeal airway of a 6-week-old infant with a history of previous endotracheal intubation. Postintubation granuloma formation in this region has not been previously reported in infants.     

Hereditary angioneurotic edema of the larynx

Hereditary angioneurotic edema (HAE) is an autosomal dominant disease resulting from a deficiency of functional C1-esterase inhibitor. If not recognized promptly and treated properly the disease can result in a fatal outcome as it causes laryngeal edema, which can lead to a life-threatening acute upper airway obstruction. We present the case of a 37-year-old female with HAE of the larynx, who was diagnosed early and treated properly, together with a review of the literature.