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Aourarh B, Aourarh A, Belkouchi L, Saouab R, Essaoudi MA. Esophageal neuroendocrine carcinoma: A clinical perspective on a rare and challenging disease. Radiol Case Rep 2025; 20:3021-3023. [PMID: 40230713 PMCID: PMC11994303 DOI: 10.1016/j.radcr.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 02/24/2025] [Accepted: 03/01/2025] [Indexed: 04/16/2025] Open
Abstract
Neuroendocrine carcinomas (NECs) of the esophagus are exceptionally rare, comprising only 0.04% of all neuroendocrine tumors. These malignancies can remain asymptomatic or manifest through digestive symptoms such as dysphagia and abdominal discomfort. Due to their rarity, limited studies exist, resulting in insufficient knowledge about their prognosis and treatment, with conflicting data in the literature. This report presents the case of a 62-year-old male chronic smoker with chronic dysphagia. Diagnostic evaluations, including gastroscopy and CT, revealed a circumferential lesion in the lower esophagus. Histopathological analysis confirmed a diagnosis of poorly differentiated large-cell neuroendocrine carcinoma. Esophageal NECs are aggressive and poorly understood tumors. Tumor size, lymph node involvement, and metastatic status are critical factors influencing treatment decisions. However, there are no established guidelines for their management. Extensive research is urgently needed to develop standardized treatment approaches and improve the prognosis of patients with high-grade esophageal NECs.
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Affiliation(s)
- Benayad Aourarh
- Department of Gastroenterology I, Mohammed V Military Hospital, Mohammed V University, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco
| | - Aziz Aourarh
- Department of Gastroenterology I, Mohammed V Military Hospital, Mohammed V University, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco
| | - Lina Belkouchi
- Department of Radiology, Mohammed V Military Hospital, Mohammed V University, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco
| | - Rachida Saouab
- Department of Radiology, Mohammed V Military Hospital, Mohammed V University, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco
| | - Mohamed Amine Essaoudi
- Department of Pathology, Mohammed V Military Hospital, Mohammed V University, Faculty of medicine and Pharmacy of Rabat, Rabat, Morocco
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Wang B, Si Y, Dou Y, Li Y, Liu Z, Huang C, Xu X. Clinical and pathological characteristics of gastric large cell neuroendocrine carcinoma: A report of 2 cases series and literature review. Medicine (Baltimore) 2024; 103:e39851. [PMID: 39465709 PMCID: PMC11460907 DOI: 10.1097/md.0000000000039851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Indexed: 10/29/2024] Open
Abstract
RATIONALE Gastric large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive neuroendocrine carcinoma that arises from the stomach and with high malignancy. Patients with gastric LCNEC usually have a poor prognosis. The standard treatment plan has not been established and its curative effect is poor. The present study described 2 cases diagnosed with gastric LCNEC and reviewed in depth the literature to improve our understanding more about this uncommon tumor and further to provide more experience to diagnose and treat this disease. PATIENT CONCERNS The present study reported 2 cases of gastric LCNEC in male patients aged 51 and 73 years old, respectively. Both patients had epigastric discomfort, pain, acid reflux and heartburn. The medical history was unremarkable. DIAGNOSES The ulcerative lesion located at gastric was examined in the 2 patients by taking the esophagogastroduodenoscopy (EGO), computed tomography (CT) and digital gastrointestinal radiography (GI), that both were suspected gastric malignancy. Endoscopic biopsies of the tumor led to the initial diagnosis of gastric cancer. Postoperative pathological and immunohistochemical examinations of the surgical specimens confirmed that 1 case had mixed adeno-neuroendocrine carcinoma (MANEC) and the other had LCNEC. INTERVENTIONS Both patients underwent surgical resection and received etoposide-cisplatin combination chemotherapy following surgery. OUTCOMES The operation was successful. Both patients had uneventful recoveries following surgery, and had been followed-up regularly. The general condition was satisfactory, and no tumor metastasis was observed at present.
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Affiliation(s)
- Bo Wang
- Department of Pathology, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Yuan Si
- Endoscopic Center, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Yan Dou
- Department of Pathology, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Yongcai Li
- Department of Computed Tomography and Magnetic Resonance Imaging, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Zhongxin Liu
- Department of Pathology, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Chaokang Huang
- Department of Pathology, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
| | - Xin Xu
- Department of Pathology, Xingtai People’s Hospital, Hebei Medical University Affiliated Hospital, Xingtai, Hebei, P.R. China
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Zhong L, Pan Y, Han S, Qi Q, Liao H, Jiang Y, Shen J. The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma. Indian J Cancer 2023; 60:512-520. [PMID: 38206083 DOI: 10.4103/ijc.ijc_151_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 03/01/2021] [Indexed: 01/12/2024]
Abstract
PURPOSE The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. METHODS Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. RESULTS In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). CONCLUSIONS Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.
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Affiliation(s)
- Liping Zhong
- Department of Medical Oncology, Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Zhejiang, China
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Zhang Y, Liao JT, Lin Y, Liu C, Wu ZH, Yu B, Sun S, Yu H, Hui XH, Wu XH, Zhao XM, Wang HJ, Zheng Q, Li Y, Hu ZH, Wang JL. Clinicopathological features, treatment modalities, and prognosis of esophageal neuroendocrine carcinoma: A single-center retrospective study. J Dig Dis 2023; 24:472-479. [PMID: 37596865 DOI: 10.1111/1751-2980.13219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 08/09/2023] [Accepted: 08/16/2023] [Indexed: 08/20/2023]
Abstract
OBJECTIVES Esophageal neuroendocrine carcinoma (ENEC) is a rare cancer that is highly malignant and related to a poor prognosis. In this retrospective study we aimed to elucidate the clinical characteristics, diagnosis and management of patients with ENEC and to evaluate the potential prognostic factors. METHODS Altogether 82 patients diagnosed with ENEC between January 2009 and December 2020 at the Fudan University Shanghai Cancer Center were retrospectively enrolled. Patients' survival was analyzed using the Kaplan-Meier and log-rank methods. Univariate and multivariate analyses and a Cox regression model were used to identify the prognostic factors. RESULTS The median overall survival (mOS) was 13 months in all patients. Multivariate analysis revealed that advanced tumor stage (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.07-6.66, P = 0.0353), liver (HR 3.36, 95% CI 1.53-7.41, P = 0.0026) and lung metastasis (HR 3.37, 95% CI 1.20-9.51, P = 0.0214) were associated with a poor prognosis. While positive chromogranin A (CgA) expression was related to a favorable outcome (HR 0.21, 95% CI 0.09-0.49, P < 0.001). Also, patients had adjustment of chemotherapy (dose reduction or less than three cycles) were prone to a worse prognosis compared with those did not (HR 4.36, 95% CI 2.10-9.08, P < 0.001). CONCLUSION In patients with ENEC, advanced cancer stage, adjustment of chemotherapy, liver and lung metastasis were associated with a poor survival, while CgA expression was related to a favorable prognosis.
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Affiliation(s)
- Yao Zhang
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiao Tao Liao
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ying Lin
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chang Liu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhen Hua Wu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Bo Yu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Si Sun
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hui Yu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao Hua Hui
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiang Hua Wu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xin Min Zhao
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hui Jie Wang
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qiang Zheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yuan Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhi Huang Hu
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jia Lei Wang
- Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Thoracic Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Cheng Y, Zhang X, Zhou X, Xu K, Lin M, Huang Q. Differences in clinicopathology and prognosis between gastroesophageal junctional and gastric non-cardiac neuroendocrine carcinomas: a retrospective comparison study of consecutive 56 cases from a single institution in China. Am J Cancer Res 2022; 12:4737-4750. [PMID: 36381336 PMCID: PMC9641387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 10/12/2022] [Indexed: 06/16/2023] Open
Abstract
Gastric neuroendocrine carcinoma (NEC), including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), is uncommon and differences in clinicopathological features and outcomes of NEC arising in various gastric regions remain elusive. We investigated 56 consecutive NECs identified among 3961 gastrectomies performed at our center between 2005 and 2021. We then compared clinicopathological characteristics and prognosis between gastroesophageal junctional (GEJ) NECs (N=39) and gastric non-cardiac NECs (N=17). No significant difference was found between the two groups in age, gender, tumor size, mixed non-neuroendocrine carcinoma component, MiNEN, NEC type, metastatic NEC component in lymph nodes, tumor infiltrating lymphocyte, lymph node metastasis, lymphovascular or perineural invasion, intestinal metaplasia in adjacent non-neoplastic mucosa, and expression of P53, PD-L1, TTF-1, HER2, and Ki-67. However, compared to gastric non-cardiac NECs, GEJ NECs displayed a significantly higher frequency of prevalence (2.79% versus 0.66%), pT3-T4 (92.3% versus 64.7%), advanced pathological stage (IIb-IV) (76.9% versus 47.1%), and a significantly lower 5-year overall survival rate (46.1% versus 73.1%) (P<0.05). The GEJ location was the only independent risk factor for overall survival. In stage-stratified comparisons, patients with stage II GEJ NEC demonstrated a significantly lower 5-year survival rate than those with gastric non-cardiac NEC at the same stage. Compared to non-NECs matched for age, gender, tumor location, and pathological summary stage, GEJ NEC was associated with significantly worse prognosis. In conclusion, GEJ NEC showed deeper invasion, more advanced pathological stages, and worse prognosis than gastric non-cardiac NEC. The findings provide pathologic evidence for individualized management strategies for patients with GEJ NEC. Future studies with larger samples are needed.
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Affiliation(s)
- Yuqing Cheng
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
| | - Xinwen Zhang
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
- Graduate School of Dalian Medical UniversityDalian, Liaoning, China
| | - Xiaoli Zhou
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
| | - Kequn Xu
- Department of Oncology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
| | - Min Lin
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
| | - Qin Huang
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou, Jiangsu, China
- Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Harvard Medical School and Brigham and Women’s HospitalBoston, Massachusetts, USA
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Vest M, Shah D, Nassar M, Niknam N. Neuroendocrine Carcinoma of the Esophagus With Liver Metastasis: A Case Report. Cureus 2022; 14:e28842. [PMID: 36225482 PMCID: PMC9536476 DOI: 10.7759/cureus.28842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2022] [Indexed: 11/05/2022] Open
Abstract
Neuroendocrine carcinoma (NEC) of the esophagus is a rare and aggressive malignancy. It is challenging to manage NEC due to its rarity. NEC may be asymptomatic or present with various symptoms such as dysphagia, abdominal discomfort, weight loss, melena, hot flushes, or diarrhea. We present the case of a 55-year-old male with a large cell neuroendocrine carcinoma of the esophagus. His aggressive and rapid progression of neuroendocrine carcinoma of the esophagus resulted in a poor clinical outcome.
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Affiliation(s)
- Mallorie Vest
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals Queens, New York City, USA
| | - Deesha Shah
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals Queens, New York City, USA
| | - Mahmoud Nassar
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals Queens, New York City, USA
| | - Negar Niknam
- Gastroenterology, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals Queens, New York City, USA
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7
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Gushima R, Miyamoto H, Imamura M, Sonoda T, Matsuno K, Yamasaki A, Furuta Y, Hashigo S, Tateyama M, Naoe H, Tanaka Y. Mixed Neuroendocrine Non-Neuroendocrine Neoplasm Arising in the Ectopic Gastric Mucosa of Esophagus. Case Rep Gastroenterol 2022; 16:637-645. [PMID: 36605731 PMCID: PMC9808311 DOI: 10.1159/000527699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 10/12/2022] [Indexed: 12/12/2022] Open
Abstract
Esophageal neuroendocrine neoplasms are extremely rare, and their prognosis is poor. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are even more rare and are defined as tumors consisting of neuroendocrine carcinoma and either adenocarcinoma or squamous cell carcinoma. We report a rare case featuring endoscopic submucosal dissection (ESD) for an esophageal MiNEN, arising from the ectopic gastric mucosa in the lower thoracic esophagus. A 92-year-old male patient was referred to this hospital for investigation of an esophageal tumor. An endoscopic examination revealed a 10 mm elevated lesion, with 8 mm flat areas on the anal side, within the ectopic gastric mucosa located in the lower thoracic esophagus. ESD was carried out, and a histopathological examination revealed a tubular adenocarcinoma composed of differentiated neuroendocrine cells. Immunohistochemical staining was positive for synaptophysin and negative for chromogranin A. The labeling index of Ki-67 was more than 80%. Based on these results, we diagnosed the lesion as an esophageal MiNEN, arising in the ectopic gastric mucosa of the esophagus. The patient remains alive, without recurrence of cancer, 24 months after ESD.
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Affiliation(s)
- Ryosuke Gushima
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideaki Miyamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Miyuki Imamura
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Sonoda
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenshi Matsuno
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Yamasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoki Furuta
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shunpei Hashigo
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masakuni Tateyama
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideaki Naoe
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Tang N, Feng Z. Endoscopic submucosal dissection combined with adjuvant chemotherapy for early-stage neuroendocrine carcinoma of the esophagus: A case report. World J Clin Cases 2022; 10:3164-3169. [PMID: 35603334 PMCID: PMC9082696 DOI: 10.12998/wjcc.v10.i10.3164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 10/25/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine carcinoma (NEC) of the esophagus is rare and highly aggressive, and lacks biological features. Currently, there are no established standard treatments for this cancer. In this report, we describe a patient with large-cell NEC of the esophagus who was successfully treated using endoscopic submucosal dissection (ESD) combined with adjuvant chemotherapy.
CASE SUMMARY A 55-year-old woman presented with intermittent mild dysphagia for 2 mo. Gastroscopy revealed a disc-shaped protruding lesion about 18 mm × 18 mm in size on the upper esophagus. Endoscopic ultrasonography demonstrated that the bulged lesion originated from the muscularis mucosa. We assessed en bloc resections using ESD for therapeutic diagnosis to devise a safe and appropriate treatment. Histopathological examination revealed a poorly differentiated neoplasm comprising of large cells with marked nuclear atypia and multifocal necrosis. In addition, the specimens had a negative horizontal margin and vertical margins. Depth of invasion was classified as submucosa 2 (SM2) without lymphovascular invasion. These histopathological results were consistent with a diagnosis of esophageal NEC, large cell type. Adjuvant therapy has been considered for ESD patients with SM2/SM3 lesions and patients with poorly differentiated lesions. After comprehensive consideration, we initiated combination treatment, i.e., ESD plus adjuvant chemotherapy. The patient remained disease-free at the 2-year follow-up.
CONCLUSION En bloc resection approach using ESD may play a vital role as a diagnostic and therapeutic modality for esophageal NEC.
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Affiliation(s)
- Nan Tang
- Department of Gastroenterology, Shanghai Xuhui Center Hospital, Shanghai 200031, China
| | - Zhen Feng
- Department of Gastroenterology, Shanghai Xuhui Center Hospital, Shanghai 200031, China
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Galanis I, Simou M, Floros G. Large-Cell Esophageal Neuroendocrine Carcinoma: Report of a Rare Case. Cureus 2022; 14:e22041. [PMID: 35340509 PMCID: PMC8913815 DOI: 10.7759/cureus.22041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2022] [Indexed: 12/02/2022] Open
Abstract
Neuroendocrine tumors (NETs) are neoplasms with neuroendocrine characteristics such as secretion of neuropeptides, large secretory vesicles, and a lack of neural structures. Neuroendocrine carcinoma (NEC) of the esophagus is a very rare malignancy. We present the case of a 58-year-old male with a pure large cell NEC of the esophagus.
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Basu S, Sitani K. High-grade esophageal neuroendocrine neoplasm with waxing and waning disease course and differential response to chemotherapy: Dual tracer positron emission tomography-computed tomography (18F-flurodeoxyglucose and 68Ga-DOTATATE) features and disease monitoring with functional molecular imaging. JOURNAL OF RADIATION AND CANCER RESEARCH 2022. [DOI: 10.4103/jrcr.jrcr_51_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Immunohistochemical Staining With Neuroendocrine Markers is Essential in the Diagnosis of Neuroendocrine Neoplasms of the Esophagogastric Junction. Appl Immunohistochem Mol Morphol 2021; 29:454-461. [PMID: 33480601 DOI: 10.1097/pai.0000000000000906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 12/20/2020] [Indexed: 12/13/2022]
Abstract
Neuroendocrine neoplasms (NENs) of the esophagogastric junction (EGJ) are uncommon and the classification of these tumors has been revised several times. Since 2016, at the Department of Pathology, Rigshospitalet, Denmark, all adenocarcinomas and poorly differentiated carcinomas of the EGJ have been stained routinely with the neuroendocrine markers, synaptophysin and chromogranin A, to detect a possible neuroendocrine component. This study aimed to determine if routine immunohistochemical staining is necessary to detect neuroendocrine differentiation of the EGJ tumors by evaluating how often a neuroendocrine component of the tumors was correctly identified or missed on routine hematoxylin and eosin-stained slides, and by evaluating the interobserver agreement among several pathologists. Of 262 cases a NEN was identified in 24 (9.2%). Up to 22.7% of all EGJ NENs would have been missed without routinely performed neuroendocrine staining in all EGJ tumors. The interobserver agreement between 3 pathologists was slight to moderate. In conclusion, immunohistochemical staining with neuroendocrine markers is essential for the diagnosis of NENs, and to detect all NENs, we recommend to perform this routinely on all resected tumors of the EGJ.
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12
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Cai MY, Cardoso MF, Zhu Y, Zhong YS, Zhou PH. An esophageal submucosal tumor treated with submucosal tunneling endoscopic resection: an unexpected result. Gastroenterol Rep (Oxf) 2020; 9:269-271. [PMID: 34316377 PMCID: PMC8309675 DOI: 10.1093/gastro/goaa073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 03/30/2020] [Indexed: 11/24/2022] Open
Affiliation(s)
- Ming-Yan Cai
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | | | - Yan Zhu
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Yun-Shi Zhong
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Ping-Hong Zhou
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
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13
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Zhou Y, Hou P, Zha KJ, Wang F, Zhou K, He W, Gao JB. Prognostic value of pretreatment contrast-enhanced computed tomography in esophageal neuroendocrine carcinoma: A multi-center follow-up study. World J Gastroenterol 2020; 26:4680-4693. [PMID: 32884225 PMCID: PMC7445868 DOI: 10.3748/wjg.v26.i31.4680] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/22/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The rare incidence of esophageal neuroendocrine carcinoma (NEC) and limited treatment experience result in insufficient clinical observations and unsuitable guidelines for its management.
AIM To investigate the prognostic value of pretreatment contrast-enhanced computed tomography (CT) characteristics in patients with esophageal NEC.
METHODS Seventy-seven esophageal NEC patients who received contrast-enhanced CT at two hospitals were enrolled in this study from June 2014 to December 2019. The clinical features and image characteristics were recorded accordingly. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank test, and multivariate analysis was carried out with a Cox proportional hazards model.
RESULTS The multivariate analysis performed using the Cox proportional hazards model showed that N stage, adjuvant chemotherapy, and degree of enhancement were independent prognostic factors for overall survival (OS). Meanwhile, adjuvant chemotherapy was an independent prognostic factor for progression-free survival (PFS). The hazard ratios (HRs) of N stage, adjuvant chemotherapy, and degree of enhancement (mild vs moderate/marked) for OS were 0.426 (P = 0.024), 3.862 (P = 0.006), and 2.169/0.809 (P = 0.037), respectively. The HR of adjuvant chemotherapy for PFS was 6.432 (P < 0.001). Adjuvant chemotherapy was significantly associated with degree of enhancement (P = 0.018).
CONCLUSION Adjuvant chemotherapy is an independent prognostic factor for OS and PFS. Additionally, N stage and degree of enhancement are prognostic factors for OS in patients with esophageal NEC.
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Affiliation(s)
- Yue Zhou
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Ping Hou
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Kai-Ji Zha
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Feng Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Kun Zhou
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Wei He
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
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14
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Treatment strategies for neuroendocrine carcinoma of the upper digestive tract. Int J Clin Oncol 2020; 25:842-850. [PMID: 32036480 DOI: 10.1007/s10147-020-01631-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 01/30/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy. METHODS Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12). RESULTS Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively. CONCLUSIONS A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.
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15
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Zhang G, Wu B, Wang X, Li J. A competing-risks nomogram and recursive partitioning analysis for cause-specific mortality in patients with esophageal neuroendocrine carcinoma. Dis Esophagus 2019; 32:5304731. [PMID: 30715226 DOI: 10.1093/dote/doy129] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Indexed: 12/11/2022]
Abstract
The objective of this study is to estimate the probability of cause-specific mortality using a competing-risks nomogram and recursive partitioning analysis in a large population-based cohort of patients with esophageal neuroendocrine carcinoma. The surveillance, epidemiology and end results database was used to identify 162 patients diagnosed with esophageal neuroendocrine carcinoma from 1998 to 2014. We estimated a cumulative incidence function for cause-specific mortality. A nomogram was constructed by using a proportional subdistribution hazard model, validated using bootstrap cross-validation, and evaluated with a decision curve analysis to assess its clinical utility. Finally, we performed risk stratification using a recursive partitioning analysis to divide patients with esophageal neuroendocrine carcinoma into clinically useful prognostic groups. Tumor location, distant metastasis, surgery, radiotherapy, and chemotherapy were significantly associated with cause-specific mortality. The calibration plots demonstrated good concordance between the predicted and actual outcomes. The discrimination performance of a Fine-Gray model was evaluated by using the c-index, which was 0.723 for cause-specific mortality. The decision curve analysis ranged from 0.268 to 0.968 for the threshold probability at which the risk model provided net clinical benefits relative to hypothetical all-screening and no-screening scenarios. The risk groups stratified by a recursive partitioning analysis allowed significant distinction between cumulative incidence curves. We determined the probability of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and developed a nomogram and recursive partitioning analysis stratification system based on a competing-risks model. The nomogram and recursive partitioning analysis appear to be suitable for risk stratification of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and will help clinicians to identify patients at increased risk of cause-specific mortality to guide treatment and surveillance decisions.
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Affiliation(s)
- G Zhang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - B Wu
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - X Wang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - J Li
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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16
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Kikuchi Y, Shimada H, Yamaguchi K, Igarashi Y. Systematic review of case reports of Japanese esophageal neuroendocrine cell carcinoma in the Japanese literature. Int Cancer Conf J 2019; 8:47-57. [PMID: 31149547 PMCID: PMC6498360 DOI: 10.1007/s13691-019-00359-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 01/17/2019] [Indexed: 12/18/2022] Open
Abstract
Esophageal neuroendocrine cell carcinoma (NEC) is extremely rare, and its treatment strategy has not been established. Systematic review and meta-analysis were carried out to assess the treatment and prognosis of patients with esophageal NEC in Japan. The Ichushi-Web database was searched from January 1964 to May 2018. In total, 141 cases of esophageal NEC were included in the analysis. The survival of the chemotherapy group with stage II/III esophageal NEC was better than that of the surgery group. Meanwhile, the survival of the adjuvant treatment group with stage II/III esophageal NEC was significantly better than that of the surgery alone group. In patients with stage IV esophageal NEC, no significant differences were observed in terms of treatment response from the three regimens: irinotecan/platinum and etoposide/platinum compared with 5-fluorouracil/platinum. Moreover, no significant differences were observed in the survival of patients who received the chemotherapy regimens. However, the 2-year survival rates of the irinotecan/platinum (26%) group and etoposide/platinum (27%) group were higher than that of the 5-fluorouracil/platinum (0%) group. In esophageal NEC, chemotherapy may be used as the first-line treatment. Irinotecan/platinum or etoposide/platinum can be the first-line regimen for chemotherapy. However, the additive effects of surgery remain unclear.
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Affiliation(s)
- Yoshinori Kikuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
- Department of Clinical Oncology, Toho University Graduate School of Medicine, Toho University, Tokyo, Japan
| | - Hideaki Shimada
- Department of Clinical Oncology, Toho University Graduate School of Medicine, Toho University, Tokyo, Japan
- Department of Surgery, School of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 142-8541 Japan
| | - Kazuhisa Yamaguchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
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17
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Zhang P, Wang W, Lu M, Zeng C, Chen J, Li E, Tan H, Wang W, Yu X, Tang Q, Zhao J, Shen L, Li J. Clinicopathological features and outcome for neuroendocrine neoplasms of gastroesophageal junction: A population-based study. Cancer Med 2018; 7:4361-4370. [PMID: 30062861 PMCID: PMC6143924 DOI: 10.1002/cam4.1702] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 07/01/2018] [Accepted: 07/03/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Gastroesophageal Junction neuroendocrine neoplasms (GEJ-NENs) are rare and heterogeneous tumors. We aim to analyze the clinicopathlogical features and prognostic factors of GEJ-NENs and to compare the outcome of GEJ-NENs with other gastric NENs. METHODS A total of 297 GEJ-NENs patients were enrolled from 10 Chinese hospitals and 3152 gastric NENs patients, including 274 GEJ-NENs, were retrieved from Surveillance, Epidemiology, and End Results (SEER) database. RESULTS The clinical characteristics of GEJ-NENs among different races were different. All Chinese patients had GEJ-NENs of grade 3, with 67.7% of poorly differentiated NEC and 32.3% of MANEC. In SEER database, 70.8% of white, 62.5% of black, and 87.5% of AP patients had poorly differentiated/undifferentiated tumors. In Cox multivariate analysis, NEC/MANEC (HR 2.09, 95%CI 1.24-3.56; P = 0.006), lymph node metastasis (HR 3.52, 95%CI 1.68-7.34; P = 0.001), and distant metastases (HR 3.90, 95%CI 2.50-6.08; P < 0.001) are independent predictors of overall survival. Surgical resection showed a median OS improvement of 13.1-73.3 months (HR 0.21, 95% CI 0.14-0.33, P < 0.001). Adjuvant therapy did not improve survival for postoperative GEJ-NEN patients (P = 0.141). GEJ-NENs were larger, higher grade, more distant metastasis, and worse prognosis than other gastric NENs. CONCLUSION GEJ-NENs were mostly poorly differentiated carcinomas, and all of Chinese patients were NEC/MANEC. The outcome of MANEC was preferable to NECs. Both lymph nodes metastasis and distant disease were independent predictors of prognosis. Surgical resection can improve survival, but postoperative adjuvant therapy had no additional benefit. GEJ-NENs have worse survival than other gastric NENs.
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Affiliation(s)
- Panpan Zhang
- Beijing Cancer HospitalPeking University Cancer Hospital & InstituteBeijingChina
| | - Wei Wang
- Sun Yat‐sen University Cancer CenterGuangzhouChina
| | - Ming Lu
- Beijing Cancer HospitalPeking University Cancer Hospital & InstituteBeijingChina
| | | | - Jie Chen
- The First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Enxiao Li
- The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | | | | | - Xianjun Yu
- Fudan University Shanghai Cancer CenterShanghaiChina
| | | | | | - Lin Shen
- Beijing Cancer HospitalPeking University Cancer Hospital & InstituteBeijingChina
| | - Jie Li
- Beijing Cancer HospitalPeking University Cancer Hospital & InstituteBeijingChina
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