Neuroendocrine Carcinoma Of Larynx Research Articles

Primary Small Cell Neuroendocrine Carcinoma of Larynx: An Atypical Case Presentation

Neuroendocrine tumors account for <1% of all malignant tumors that can originate from any part of the body, most frequently diagnosed in the lung. Extrapulmonary presentation is rare, common sites are genitourinary and gastrointestinal. According to the 2017 WHO proposed classification, small cell type (SCNEC) is a poorly differentiated neuroendocrine carcinoma. The most common site in the head and neck is the larynx, accounts for <0.6%. Small cell neuroendocrine carcinomas are extremely rare entity of laryngeal cancers. We report a case of small cell neuroendocrine carcinoma of larynx.

Primary Surgical Management of Laryngeal Neuroendocrine Neoplasms: A Single Institution Case Series.

Objective: Laryngeal neuroendocrine neoplasms (NENs) are rare diseases. A single institution retrospective study was done of the outcome of patients with laryngeal NENs who undergo primary surgery as the first treatment modality. Methods: Retrospective analysis of medical records of patients with laryngeal NENs between 2009 and 2018. Cases were classified by applying the 2022 World Health organization Classification of Head and Neck Tumors (5th edition). Results: Six patients were eligible at our tertiary center: 1 large cell neuroendocrine carcinoma (NEC), 3 small cell NEC, 1 neuroendocrine tumor grade 1, and 1 neuroendocrine tumor grade 2. All admitted patients received upfront surgeries, including 3 transoral CO2 laser surgeries and 3 total laryngectomies with or without elective neck dissection. Four patients underwent subsequent chemoradiotherapy. Although 3 patients had recurrent disease and distal metastasis, the overall survival was generally improved. Conclusion: According to our institutional experience, upfront surgery in the first-line setting of a multi-modality approach with adjuvant chemoradiotherapy plays a very important role in managing laryngeal NECs, and may confer additional survival benefit in some patients of the large cell carcinoma subgroup.

Clinical Diagnosis and Treatment of Primary Laryngeal Neuroendocrine Carcinoma.

This study aims to investigate the clinical diagnosis and treatment characteristics of primary laryngeal neuroendocrine carcinoma. A retrospective analysis was performed for the data of 6 patients with primary laryngeal neuroendocrine carcinoma admitted to the Department of Otorhinolaryngology of Dalian Central Hospital from September 2015 to January 2022, all of whom were male patients. And laryngoscopy showed that 4 had a similar appearance to hemangioma, 1 had nodular hyperplasia, and 1 was papilloma-like. The site of onset was located on the laryngeal surface of the epiglottis in 3 cases, situated in the aryepiglottic fold in 2 cases, and the posterior ventricular zone in 1 case. Five patients underwent surgery, including 4 by transoral endoscopic cryogenic plasma radiofrequency mass resection; one underwent a cervical lymph node dissection and supraglottic horizontal hemilaryngectomy. The remaining 1 case was treated in another hospital after the pathological diagnosis was confirmed by biopsy. All patients had no cervical lymph node metastases and were not supplemented with chemoradiotherapy. The postoperative pathological diagnosis of all 5 patients was neuroendocrine carcinoma. No cancer cells were seen at the margins and base. One patient was lost to follow-up after treatment in another hospitals and the rest were followed up for 6months to 6years. One patient had removed laryngeal tumor and epiglottis by a low-temperature plasma radiofrequency ablation, recurrence 1year after surgery, and no recurrence for 5years after supraglottic horizontal hemilaryngectomy combined with prophylactic cervical lymph node dissection, no recurrence for the other 4patients after 6months to 4years of follow-up. The common sites of laryngeal neuroendocrine carcinoma are the laryngeal surface of the epiglottis and the aryepiglottic fold. The appearance of the tumor is mainly similar to that of hemangioma. Moreover, a common pathological classification is atypical carcinoid tumors, where early detection and surgical treatment can achieve a good therapeutic effect.

Clinical analysis of 12 cases of laryngeal neuroendocrine carcinoma

Objective: To investigate the clinical and pathological features, treatments and prognosis of laryngeal neuroendocrine carcinoma (LNEC). Methods: We conducted the retrospective analysis of the clinical data of 12 patients with LNEC admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shanxi Medical University from May 2014 to December 2021, including 9 males and 3 females, aged 50-77 years. There were 4 cases of typical carcinoid tumour (highly differentiated), 5 cases of atypical carcinoid tumour (moderately differentiated) and 3 cases of neuroendocrine small cell carcinoma (hypofractionated). The clinical features, diagnosis, treatment and prognosis of LNEC were analysed. Results: The clinical manifestations of LNEC varied according to the tumour type but did not correlate with the pathological types. The supraglottic type was characterized by sore throat, foreign body sensation in the pharynx, coughing, obstructive sensation when eating and choking on water. The treatments were determined according to the pathological types, lesion location and invasion scope. Of 12 patients 4 underwent horizontal partial laryngectomy plus elective lymphatic dissection plus postoperative radiotherapy/chemotherapy, 4 underwent vertical partial laryngectomy (3 of them with cervical lymphatic dissection), 3 underwent supported laryngoscopic plasma laryngectomy for laryngeal cancer, and 1 abandoned for treatment. With the follow-up of 8 -78 months, 5 patients were alive, 1 died from chemotherapy reactions, 3 died from other diseases, 1 died from lung metastasis, 1 died from lung infection and 1 was lost to follow-up. Conclusion: LNEC is clinically rare, the clinical manifestations are less specificity, diagnosis relies on pathological and immunohistochemical examinations, and treatment modalities and prognoses are closely related to the pathological subtypes of LNEC.

A Case of Large Cell Neuroendocrine Carcinoma in Posterior Supraglottis

Neuroendocrine carcinoma (NEC) is a rare form of hormone-secreting tumor. NECs originate from the epithelial cells of the larynx and account for less than 1% of the laryngeal neoplasm. Most cases of NECs are diagnosed by pathological confirmation after surgery. The terminology of laryngeal NEC has been a source of confusion. In 2017, World Health Organization newly categorized laryngeal NEC; as a result, the large cell type, which has been the main target of disagreement, was finally included into a subtype of poorly differentiated NEC. We report a case of a 58-year-old male with a growing granulomatous mass in the posterior supraglottis. The granuloma was removed by surgical excision when the size of the mass increased. He was diagnosed with the large cell type laryngeal NEC by pathological confirmation. He underwent postoperative radiotherapy and is currently being followed up in our outpatient clinic without evidence of recurrence.

Poorly Differentiated Neuroendocrine Larynx Carcinoma: Clinical Features and miRNAs Signature-A New Goal for Early Diagnosis and Therapy?

Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous malignancies presenting a wide range of pathological and clinical manifestations. Herein, we retrospectively characterize ten patients diagnosticated with LNEC, five of which were defined as well-moderately differentiated neuroendocrine carcinomas, and five that were defined as poorly differentiated neuroendocrine carcinomas, according to the latest WHO classification. Clinical features were analyzed and compared between the two subgroups together with a microRNA study which evidenced a peculiar signature likely related to poorly differentiated larynx neuroendocrine carcinomas. These findings may offer new useful insights for clinicians to improve diagnosis efficiency, therapy response, and patients’ outcome for this aggressive neoplasm.

Neuroendocrine carcinoma of the larynx with Lambert-Eaton myasthenic syndrome: a rare case report and literature review

This current report describes a rare clinical case of neuroendocrine carcinoma (NEC) of the larynx with associated Lambert-Eaton myasthenic paraneoplastic syndrome (LEMS). A 68-year-old male patient presented with severe dysphonia and dysphagia. He underwent a total laryngectomy and the excised lesion was extremely large. A pathological examination demonstrated ‘morphological findings of a poorly differentiated carcinoma (G3) with aspects of neuroendocrine differentiation’ (i.e. a poorly differentiated neuroendocrine carcinomas [PD-NEC]). Based on the patient’s medical history and the immunohistochemical findings, he was treated with three cycles of neoadjuvant chemotherapy (cisplatin–etoposide) and then radiotherapy with a total dose of 70 Gy. Of the 10 cases of paraneoplastic syndrome (PNS) related to laryngeal NEC reported in the literature, nine of these syndromes were of an endocrine type. Only one case of PNS associated with laryngeal cancer had a neurological manifestation, which was LEMS. To the best of our knowledge, this current case has only one similar precedent in the literature and it is the second report of an association between a PD-NEC and LEMS. Laryngeal NECs are rare lesions with different prognostic characteristics. The diagnosis should be made using an endocrinological, neurological, radiological and histological multidisciplinary approach. A radical surgical approach is recommended.

Application of INSM1 in Diagnosis and Grading of Laryngeal Neuroendocrine Carcinoma.

Chromogranin (CHG), synaptophysin (Syn), and CD56 are generally used in a panel to support diagnoses of laryngeal neuroendocrine carcinomas (NECs). However, the absence of expression of these markers does not completely exclude the diagnosis. INSM1 is a novel marker that is considered sufficiently sensitive and specific for NE differentiation. The aim of this study is not only to detect its sensitivity and specificity, but also to evaluate its application in grading for laryngeal NECs. The clinicopathological characteristics of the 25 cases with laryngeal NECs were retrospectively analyzed. The expressions of INSM1, CHG, Syn, and CD56 were detected by immunohistochemistry. Of the 25 laryngeal NECs, INSM1 had higher sensitivity (92%) than Syn (84%), CHG (76%) and CD56 (76%). The average H scores of INSM1, CD56, Syn, and CHG were 160, 37.5, 300, 300 for well-differentiated neuroendocrine carcinoma (WD-NEC); 190, 149, 209, 215 for moderately differentiated neuroendocrine carcinoma (MD-NEC); 251, 208, 104, 25 for poorly differentiated neuroendocrine carcinoma with small cell (SCNEC); 109, 160, 98, 26 for large cell types (LCNEC), respectively. Of these 98 non-neuroendocrine tumors, INSM1 expression was seen in nine (9%) tumors, all were squamous cell carcinoma. And INSM1 staining was generally focal. INSM1 has high sensitivity and specificity in diagnosis of laryngeal NECs. For grading laryngeal NECs, Syn and CHG showed significant advantages in the diagnosis of WD-NEC and MD-NEC, whereas INSM1 and CD56 showed greater diagnostic value in the diagnosis of SCNEC and LCNEC, especially in SCNEC. 4 Laryngoscope, 131:E2662-E2668, 2021.

Update on Neuroendocrine Carcinomas of the Larynx.

Laryngeal neuroendocrine carcinomas are heterogeneous neoplasms characterized by neuroendocrine differentiation. Their prognoses are dependent on tumor type, therefore different classifications have been developed. Moreover, other tumors have overlapping pathologic features posing a range of diagnostic possibilities. A review of the literature was performed to comprehensively understand the classification and diagnosis of these tumors. We review the past and present classification systems, with emphasis to the latest 2017 World Health Organization Classification of Head and Neck Tumors. We highlight salient clinicopathologic features and discuss the presumptive etiologic role of human papilloma virus. We share a practical algorithmic approach to the diagnosis of suspected neuroendocrine neoplasms of the larynx including a novel marker for neuroendocrine differentiation, insulinoma-associated protein 1. Accurate diagnosis and grading of laryngeal neuroendocrine carcinomas is critical for prognostication and therapeutic decision making. The use of an algorithm is instrumental in assuring the exclusion of mimickers.

Carcinomas atípicos de la laringe. Descripción de dos casos

Introduction and objective: 95% of the malignant neoplasm of the larynx are squamous carcinoma. Neuroendocrine carcinomas correspond to at least 1 % of laryngeal tumors. The supraglottic is the most frequent laryngeal localization. Diagnosis is based on histological and immunohistochemically characteristic. They are divided into four histological types, which have a different natural evolution and prognosis. Description: We present two cases of laryngeal neuroendocrine carcinomas. One of them belongs to a small cell neuroendocrine carcinoma and the other one to a large cell carcinoma, which diagnosis generated controversy.

Metastatic large cell neuroendocrine carcinoma of larynx: Individualizing tumor biology by dual tracer positron emission tomography/computed tomography (68Ga-DOTATATE and 18F-fluorodeoxyglucose) molecular imaging and disease stabilization following 177Lu-DOTATATE peptide receptor radionuclide therapy after initial progression on chemoradiotherapy

Metastatic large cell neuroendocrine carcinoma of larynx: Individualizing tumor biology by dual tracer positron emission tomography/computed tomography (⁶⁸Ga-DOTATATE and ¹⁸F-fluorodeoxyglucose) molecular imaging and disease stabilization following ¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy after initial progression on chemoradiotherapy

Large Cell Neuroendocrine Carcinoma of the Larynx: A Case Report and Review of Literature

Laryngeal neuroendocrine carcinomas (LNEC) constitute <1% of all tumours originating from the larynx and are believed to originate from pluripotential stem cells located in the submucosa of the larynx. It is hard to estimate the true incidence of large-cell neuroendocrine carcinoma (LCNEC) because the WHO classification does not make a distinction between atypical carcinoid tumors and large-cell neuroendocrine carcinoma. In the current classification, laryngeal LCNEC is considered synonymous with atypical carcinoid/moderately-differentiated (Grade II) neuroendocrine carcinoma. This distinction is clinically important as the clinical behavior and response to treatment differs greatly between subtypes. We report a rare case of metastatic LCNEC of subglottic region of larynx who is treated with chemotherapy and radiotherapy and a review of literature on the diagnosis and treatment of these tumors is presented.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space.

Chapter3 "Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space" of the World Health Organization (WHO) Blue Book 2017 "Classification of Head and Neck Tumours" shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial-mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.

Primary large cell neuroendocrine carcinoma of the larynx

Neuroendocrine tumours (NETs) can arise in most organs of the body but are most frequently recorded in the gastrointestinal tract or lungs. They are rarely found in the head and neck region. The commonest site in the head and neck region is in the larynx. NETS in the larynx are almost invariably primary in origin. We describe a case of a middle-aged gentleman, a chronic smoker who was diagnosed with primary large cell neuroendocrine carcinoma of larynx with cervical nodal metastases. Large cell neuroendocrine carcinoma of larynx is a rare subset of NETs with a markedly more aggressive clinical course. He was initially treated with radiotherapy, and subsequently underwent total laryngectomy, total glossectomy. Right radical neck dissection and reconstruction with pectoralis major myocutaneous flap.

Calcitonin-Secreting Moderately Differentiated Neuroendocrine Carcinoma of Larynx with Solitary Papillary Thyroid Carcinoma: A Case Report with Immunohistochemical Study

A 51-year-old female presented with 2 months' history of sore throat, change in voice, odynophagia, along with neck and thyroid nodule. CT/PET scan showed thickening of epiglottis with enhancement after intravenous contrast. Laser resection of epiglottis was done and histopathology revealed moderately differentiated neuroendocrine carcinoma. A week later patient underwent total thyroidectomy with bilateral modified radical neck dissection. Adjuvant external beam radiotherapy to the larynx and neck was given post-operatively.

化学放射線療法が奏功した喉頭神経内分泌癌（NEC/G3）例

Neuroendocrine tumors is a generic term for tumors arising from neuroendocrine cells. In the present study, we encountered a patient with a Grade 3 laryngeal neuroendocrine carcinoma with liver and bone metastases who was successfully treated with a small cell lung cancer (SCLC) regimen. We report herin on this case with a review of the diagnosis, classification, and management of neuroendocrine tumors. Classically, neuroendocrine tumors have their own classification by the organs involved, and in some previous studies, the histopathology has been inconsistent with the clinical course. Then, in 2010, the WHO advocated a new pathological classification, whereby neuroendocrine tumors were to be stratified into 3 groups: Grade (G) 1, G2 and G3 based on the mitotic count and Ki67 index. A previously reported series of high-grade neuroendocrine tumors were equivalent to G3, and some reports have described that SCLC treatment was given. In our case, the patient was also treated as an SCLC patient, and the response of the primary lesion was evaluated as complete response (CR). Currently, 18 months have elapsed since the completion of therapy, the patient enjoys satisfactory levels of QOL without recurrence. We believe that this classification would be of assistance in discussion about prediction of the prognosis and statistical treatment.

A Case of Laryngeal Neuroendocrine Carcinoma (NEC/G3) which Responded Well to Chemoradiotherapy

A Case of Laryngeal Neuroendocrine Carcinoma (NEC/G3) which Responded Well to Chemoradiotherapy

High-Grade Neuroendocrine Carcinoma of the Larynx: The Mayo Clinic Experience.

To report a single institutional series of high-grade neuroendocrine carcinoma of the larynx (NCL), a very rare yet aggressive tumor. To review the management of NCL, including discussion of clinical behavior, treatment outcome, and prognosis. A retrospective chart review of high-grade laryngeal neuroendocrine carcinomas at a single institution, including small- and large-cell neuroendocrine carcinomas. A total of 8 patients with high-grade NCL treated at our institution from 1992 to 2014 were identified. The median age at diagnosis was 65.5 years (range, 43-80). Five patients were male. Two patients had a known smoking history. Primary tumor location was supraglottic in 7 patients and glottic in 1 patient. Primary treatment consisted of surgery alone (3 patients), radiotherapy alone (1 patient), combination of chemotherapy and radiotherapy (1 patient), and surgery followed by postoperative chemoradiotherapy (3 patients). Locoregional recurrence followed by distant metastasis occurred in 6 patients. Median overall survival was 44.0 months (95% CI, 3-62.0). High-grade NCL is a rare diagnosis. Compared to well- and moderately differentiated NCL, high-grade NCL has a far more aggressive clinical course and associated with a worse prognosis. To our knowledge, this is the largest series of patients with high-grade NCL treated at a single institution. Prompt diagnosis and multimodality therapy including elective neck dissection may improve survival.

Neuroendocrine carcinoma of the larynx with metastasis to the eyelid.

Neuroendocrine tumors are a rare type of neoplasms that comprise only 0.5% of all malignancies.¹ They usually arise from the gastrointestinal tract and the lung.¹,² Neuroendocrine carcinoma of the head and neck is a relatively rare malignancy described in the literature. The larynx is the most commonly affected region of the head and neck.³,⁴ Nevertheless, small-cell carcinoma comprises only 0.5% of all laryngeal cancers.⁵ Neuroendocrine carcinoma of the larynx carries variable prognosis depending on the histological subtype.⁶ Typical carcinoid rarely metastasizes, but atypical carcinoid and small-cell carcinoma have high rates of metastasis, usually in the lung and liver.² Cutaneous metastasis from neuroendocrine carcinoma is an extremely rare entity, with only few cases reported in the English literature.⁷,⁸ We report the case of an elderly man with recurrent laryngeal neuroendocrine carcinoma with metastasis to the eyelid.

Laryngeal Neuroendocrine Carcinoma: A Population-Based Analysis of Incidence and Survival.

Laryngeal neuroendocrine carcinoma (LNEC) is a rare malignancy with various subtypes, each with different characteristics. Classification of these subtypes is used to delineate treatment and management, as most are clinically aggressive with poor prognosis. This study analyzes the characteristics and survival outcomes of LNEC using population-based data. Analysis of a population-based tumor registry. Academic medical center. The Surveillance, Epidemiology, and End Results (SEER) database (1973-2011) was queried for LNEC cases. Data analyzed included patient demographics, incidence, treatment modality, and survival. In total, 257 LNEC cases were extracted from the SEER database. Sixty-three percent were male, and the mean age of diagnosis was 61.9 years. Most cases were located in the supraglottis (62.6%), were of the small cell carcinoma (52.9%) histologic subtype, and were grade IV (40.9%) and American Joint Committee on Cancer (AJCC) stage IV (59.4%). Surgery and radiotherapy were used as treatment modalities in 38.3% and 59.8% of patients, respectively. Overall 5-year disease-specific survival (DSS) for all LNEC was 30.2%, with lower grade, lower AJCC stage, and treatment with surgery having higher 5-year DSS. LNEC often presents as an aggressive tumor at an advanced stage and has poor survival outcomes. Poor prognostic factors include high histologic grade, advanced stage disease, and not undergoing surgical resection. LNEC may be best treated depending on its histologic differentiation, with surgery being beneficial for early grade tumors while radiotherapy is inconclusive in its benefit for late-stage disease.