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Díaz-López S, Jiménez-Castro J, Robles-Barraza CE, Ayala-de Miguel C, Chaves-Conde M. Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract. World J Gastrointest Oncol 2024; 16:1166-1179. [PMID: 38660639 PMCID: PMC11037054 DOI: 10.4251/wjgo.v16.i4.1166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/17/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.
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Affiliation(s)
- Sebastián Díaz-López
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | | | | | - Carlos Ayala-de Miguel
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | - Manuel Chaves-Conde
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
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Liu L, Li Q, Liu W, Qiu Z, Wu Z, Yu D, Deng W. Gastric mixed neuroendocrine non-neuroendocrine neoplasms. Front Oncol 2024; 14:1335760. [PMID: 38655135 PMCID: PMC11036886 DOI: 10.3389/fonc.2024.1335760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 03/26/2024] [Indexed: 04/26/2024] Open
Abstract
The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.
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Affiliation(s)
- Li Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Qian Li
- Department of Ultrasound Imaging, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenxuan Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zhendong Qiu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zhongkai Wu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Danli Yu
- Department of Ultrasound Imaging, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenhong Deng
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5323-5331. [DOI: 10.12998/wjcc.v11.i22.5323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer.
CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively.
CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5329-5337. [PMID: 37621602 PMCID: PMC10445072 DOI: 10.12998/wjcc.v11.i22.5329] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Nguyen THC, Nguyen Tran BS, Nguyen TP, Ha TMT, Pham NC, Nguyen TGT, Hoang H, Dang Cong T. Deficient Mismatch Repair Proteins in Gastric Mixed Neuroendocrine Non-Neuroendocrine Neoplasm: A Rare Case Report. Case Rep Oncol 2023; 16:1172-1182. [PMID: 37900850 PMCID: PMC10601832 DOI: 10.1159/000533707] [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: 07/25/2023] [Accepted: 08/16/2023] [Indexed: 10/31/2023] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare type of gastric carcinoma with controversial diagnosis and treatment. Recent data implies that deficiency mismatch repair proteins inducing microsatellite instability are considered one of the potential drivers of this disease. Hence, we report a stomach MiNEN with MMR protein loss. An admitted 60-year-old woman complained of epigastric pain. The pathological analysis of the gastro-endoscopic biopsy specimen revealed gastric adenocarcinoma. The radiological staging was cT3N1M0; therefore, she received D2 distal gastrectomy. Suspecting neuroendocrine component admix with adenocarcinoma part on the resected specimen microscopy, applying biomarkers including AE 1/3, synaptophysin, and chromogranin A to confirm the diagnosis of MiNEN. The neuroendocrine part was classified as neuroendocrine tumor grade 2 with Ki 67 at 16.5%. To further understand the molecular characterization of this disease, we evaluated mismatch protein expression by staining MLH1, MSH2, MSH6, and PMS2 antibodies. Interestingly, both components lost MLH1 and PMS2 proteins. Her radical surgery followed oxaliplatin/capecitabine adjuvant chemotherapy. The patient is still well after eight cycles of chemotherapy. dMMR gastric MiNENs and dMMR gastric cancer share many clinical and genetic characteristics. Further studies are necessary to survey the role of dMMR in the prognosis and treatment of this entity.
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Affiliation(s)
- Thi Hong Chuyen Nguyen
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Bao Song Nguyen Tran
- Department of Histology, Embryology, Pathology, and Forensic Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thanh Phuc Nguyen
- Department of Anatomy and Surgical Training, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | | | - Thu Giang Thi Nguyen
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Huu Hoang
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thuan Dang Cong
- Department of Histology, Embryology, Pathology, and Forensic Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
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Miyaguchi K, Kawasaki T, Tashima T, Ryozawa S. Mixed neuroendocrine–non‐neuroendocrine neoplasm arising from long‐segment Barrettʼs esophagus showing exceptionally aggressive clinical behavior. Cancer Rep (Hoboken) 2022; 5:e1644. [PMID: 35801304 PMCID: PMC9458485 DOI: 10.1002/cnr2.1644] [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] [Received: 01/11/2022] [Revised: 04/29/2022] [Accepted: 05/12/2022] [Indexed: 11/08/2022] Open
Abstract
Background Case Conclusion
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Affiliation(s)
- Kazuya Miyaguchi
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
| | - Tomonori Kawasaki
- Department of Pathology Saitama Medical University International Medical Center Saitama Japan
| | - Tomoaki Tashima
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
| | - Shomei Ryozawa
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
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Szekely TB, Toganel C, Kadar Z, Sava AD, Bara T, Roman D, Gurzu S. Adenosquamous and squamous cell carcinoma of the pancreas: two histopathological variants of ductal adenocarcinoma. ACTA MARISIENSIS - SERIA MEDICA 2021; 67:173-176. [DOI: 10.2478/amma-2021-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Abstract
Introduction: Primary squamous cell carcinoma (SCC) and adenosquamous carcinoma of the pancreas are rare malignancies for which diagnostic and treatment strategy are challenging. In this paper we present a literature review of these tumors based on two case reports.
Case presentation: In the first case, a 55-year-old male presented with an inoperable pancreatic head/body junction tumor. Endoscopic ultrasound-guided fine needle aspiration was practiced, and histopathological examination revealed a squamous cell carcinoma of the pancreas. After exclusion of any another tumor, the diagnosis of cT4N0M0-staged primary pancreatic SCC was made. The patient is under treatment with gemcitabine and oxaliplatin. The second case is represented by a 73-year-old patient in which imagistic examinations highlighted a cystic mass of the pancreatic body. Following coporeo-caudal splenic-pancreatectomy and histopathological-proved diagnosis of adenosquamous carcinoma, the patient started chemotherapy but died at 11 months after surgery. Both tumor components displayed positivity for markers which prove ductal (cytokeratin19, maspin) and squamous differentiation (p63, cytokeratin5/6) same as vimentin, as indicator of epithelial mesenchymal transition (EMT).
Conclusions: SCC and adenosquamous carcinoma of the pancreas are aggressive malignancies which prognosis remains highly reserved. These tumors might be variants of ductal adenocarcinomas which are dedifferentiated through EMT phenomenon.
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Affiliation(s)
| | - Cornelia Toganel
- Department of Oncology , Clinical County Hospital , Targu Mures , Romania
- Department of Oncology , George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures , Romania
| | - Zoltan Kadar
- Department of Oncology , Clinical County Hospital , Targu Mures , Romania
- Department of Oncology , George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures , Romania
| | | | - Tivadar Bara
- Department of Surgery , George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures , Romania
| | - Daniela Roman
- Department of Oncology , Clinical County Hospital , Targu Mures , Romania
| | - Simona Gurzu
- Department of Pathology , George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures , Romania
- Research Center of Oncopathology and Translational Medicine (CCOMT) , George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures , Romania
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Arencibia Pérez B, Delgado Sánchez JJ, Marchena Gómez J. Mixed adenoneuroendocrine carcinoma of the colon, complex and unique clinical duality. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:796-797. [PMID: 34154366 DOI: 10.17235/reed.2021.7873/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In relation to the article "A case of a mixed adenoneuroendocrine tumor of colon" 1, we want to contribute a new case of this exceptional and biphasic clinical entity which are the MANECs (Mixed adenoneuroendocrine carcinoma), tumors represented by the mix of pathological components highly aggressive that affect the gastrointestinal and pancreatobiliary tract characterized by the dual presence of glandular and neuroendocrine epithelial elements, where each component represents at least 30% of the tumor.
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Affiliation(s)
- Beatriz Arencibia Pérez
- Cirugía General y del Aparato Digestivo, Hospital Universitario de Gran Canaria Dr. Negrín, España
| | | | - Joaquín Marchena Gómez
- Cirugía General y del Aparato Digestivo, Hospital Universitario de Gran Canaria Dr. Negrín, España
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Grossi U, Bonis A, Carrington EV, Mazzobel E, Santoro GA, Cattaneo L, Centonze G, Gallo G, Kazemi Nava A, Romano M, Di Tanna GL, Zanus G. Mixed adenoneuroendocrine carcinoma (MANEC) of the lower gastrointestinal tract: A systematic review with Bayesian hierarchical survival analysis. Eur J Surg Oncol 2021; 47:2893-2899. [PMID: 34052038 DOI: 10.1016/j.ejso.2021.05.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/25/2021] [Accepted: 05/07/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Mixed adeno-neuroendocrine carcinomas (MANEC) are a subgroup of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) described as mixed neoplasms containing dual neuroendocrine and non-neuroendocrine components. The aim of this study was to appraise the prevalence of MANEC in the lower gastrointestinal (GI) tract and provide reliable estimates of survival. METHOD A systematic review was undertaken in accordance with PRISMA guidelines using PubMed, Embase, Cochrane Library of Systematic Review, Web of Science, and Scopus databases, and a Bayesian hierarchical survival pooled analysis was performed. RESULTS Of 182 unique records identified, 71 studies reporting on 752 patients met the inclusion criteria. Mean age was 64.2 ± 13.6, with a male-to-female ratio of 1.25. Overall, 60.3% of MANEC were located in the appendix, 29.3% in the colon, and 10.4% in the anorectum. More than a quarter (29%) of patients had stage IV disease at diagnosis, with higher prevalence in appendiceal than colonic and anorectal primaries. More than 80% had a high-grade (G3) endocrine component. Of the 152 patients followed up for a median of 20 months (interquartile range limits, 16.5-32), median overall survival was 12.3 months (95% credible interval [95%CrI], 11.3-13.7), with a 1.12 [95%CrI, 0.67-1.83] age-adjusted hazard ratio between metastatic and non-metastatic MANEC. Stage IV disease at diagnosis was more prognostically unfavorable in cases of colonic compared to anorectal origin. CONCLUSION MANEC is a clinically aggressive pathological entity. The results of this study provide new insights for the understanding of tumor location within the lower GI tract and its prognosis in terms of overall survival.
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Affiliation(s)
- Ugo Grossi
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy.
| | - Alessandro Bonis
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy
| | - Emma V Carrington
- Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Enrico Mazzobel
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy
| | | | - Laura Cattaneo
- Department of Diagnostic Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Centonze
- Department of Diagnostic Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy
| | - Andrea Kazemi Nava
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy
| | - Gian Luca Di Tanna
- Statistics Division, The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, Italy
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Huang YC, Yang NN, Chen HC, Huang YL, Yan WT, Yang RX, Li N, Zhang S, Yang PP, Feng ZZ. Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients. World J Gastroenterol 2021; 27:624-640. [PMID: 33642833 PMCID: PMC7901054 DOI: 10.3748/wjg.v27.i7.624] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/24/2020] [Accepted: 01/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is low. To improve our understanding of this rare tumor type and optimally guide clinical treatment, associated risk factors, clinical manifestations, and prognosis must be explored.
AIM To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN (GEP-MiNEN).
METHODS We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College (Anhui, China) between January 2013 and December 2017. Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models. We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors, 47 with neuroendocrine carcinomas (NEC), and 58 with poorly differentiated adenocarcinoma.
RESULTS Among the 46 patients with GEP-MiNEN, thirty-five had gastric tumors, nine had intestinal tumors (four in the small intestine and five in the colon and rectum), and two had pancreatic tumors. The median age of the patients was 66 (41-84) years, and the male-to-female ratio was 2.83. Thirty-three (71.7%) patients had clinical stage III and IV cancers. Distant metastasis occurred in 14 patients, of which 13 had metastasis to the liver. The follow-up period was 11-72 mo, and the median overall survival was 30 mo. Ki-67 index ≥ 50%, high proportion of NEC, lymph node involvement, distant metastasis, and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN. The median overall survival was shorter for patients with NEC than for those with MiNEN (14 mo vs 30 mo, P = 0.001), but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN (30 mo vs 18 mo, P = 0.453).
CONCLUSION A poor prognosis is associated with rare, aggressive GEP-MiNEN. Ki-67 index, tumor composition, lymph node involvement, distant metastasis, and clinical stage are important factors for patient prognosis.
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Affiliation(s)
- Yu-Chen Huang
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Ning-Ning Yang
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Hong-Chun Chen
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Yuan-Li Huang
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Wen-Tian Yan
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Ru-Xue Yang
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Nan Li
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
| | - Shan Zhang
- Department of Pathology, The Second People's Hospital of Hefei, Hefei 230000, Anhui Province, China
| | - Pan-Pan Yang
- Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Zhen-Zhong Feng
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China
- Department of Pathology, Bengbu Medical College, Bengbu 233000, Anhui Province, China
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Gurzu S, Jung I. Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe. Cancers (Basel) 2021; 13:cancers13030366. [PMID: 33498377 PMCID: PMC7864036 DOI: 10.3390/cancers13030366] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 01/12/2021] [Accepted: 01/19/2021] [Indexed: 02/05/2023] Open
Abstract
In this review the authors aimed to emphasize the practical value of nuclear expression of the mammary serine protease inhibitor (maspin), also known as serpin B5 protein, in colorectal carcinoma (CRC), from pre-malignant disorders to carcinogenesis and metastasis. As the role of maspin is controversial and not yet understood, the present update highlights the latest data revealed by literature which were filtrated through the daily experience of the authors, which was gained at microscopic examination of maspin expression in CRCs and other tumors for daily diagnosis. Data regarding the subcellular localization of maspin, in correlation with the microsatellite status, grade of tumor dedifferentiation, and epithelial-mesenchymal transition (EMT) phenomenon of the tumor buds were presented with details. An original observation refers to the maspin capacity to mark the tumor cells which are "at the point of budding" that were previously considered as having "hybrid EMT phenotype". It refers to the transitional status of tumor cell that is between "epithelial status" and "mesenchymal status". The second original hypothesis highlights the possible role of maspin in dysregulating the intestinal microbiota, in patients with idiopathic inflammatory bowel diseases (IBD) and inducing IBD-related CRC. The dynamic process of budding and EMT of tumor buds, possible mediated by maspin, needs further investigation and validation in many human CRC samples. The histological and molecular data reveal that synthesis of maspin-based therapeutics might represent a novel individualized therapeutic strategy for patients with CRC.
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Affiliation(s)
- Simona Gurzu
- Correspondence: ; Tel.: +40-7-4567-3550; Fax: +40-2-6521-0407
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Yang M, Zeng L, Yao WQ, Ke NW, Tan CL, Tian BL, Liu XB, Xiang B, Zhang Y. A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms. Medicine (Baltimore) 2020; 99:e22291. [PMID: 33181635 PMCID: PMC7668515 DOI: 10.1097/md.0000000000022291] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.
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Affiliation(s)
| | | | | | - Neng-wen Ke
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, the People's Republic of China
| | - Chun-lu Tan
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, the People's Republic of China
| | - Bo-le Tian
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, the People's Republic of China
| | - Xu-bao Liu
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, the People's Republic of China
| | | | - Yi Zhang
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, the People's Republic of China
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Choi NY, Kim BS, Oh ST, Yook JH, Kim BS. Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach. Am Surg 2020; 87:631-637. [PMID: 33142079 DOI: 10.1177/0003134820950000] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. METHODS This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. RESULTS DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN (P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN (P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN (P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs (P < .05 each). CONCLUSION DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.
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Affiliation(s)
- Nam Young Choi
- 443078 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Byung-Sik Kim
- 443078 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung Tae Oh
- 443078 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jeong Hwan Yook
- 443078 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Beom Su Kim
- 443078 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Yamashita S, Abe H, Kunita A, Yamashita H, Seto Y, Ushiku T. Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma. Histopathology 2020; 78:381-391. [PMID: 32767778 DOI: 10.1111/his.14230] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/28/2020] [Accepted: 08/04/2020] [Indexed: 01/10/2023]
Abstract
AIMS Gastric neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. We aim to investigate expression profiles of HER2 and programmed death ligand 1 (PD-L1) in gastric NEC to test the potential applicability of drugs targeting these molecules. METHODS AND RESULTS Expression levels of HER2 and PD-L1 were evaluated in 25 gastric NECs, including 10 pure NECs and 15 mixed adenocarcinoma-NECs, and a combined positive score (CPS) was used to evaluate PD-L1 expression. The correlations of expression levels with both clinicopathological features and the expression of p53, retinoblastoma protein (Rb) and mismatch repair proteins were also analysed. Eighteen of the 25 (72%) cases showed a PD-L1 CPS of ≥ 1, which was previously shown to be associated with response to pembrolizumab. Positive nodal metastasis and low tumour-infiltrating lymphocyte (TIL) levels at the invasive margin were significantly associated with a PD-L1 CPS of < 1. The NEC component was HER2-negative in all cases, whereas HER2 positivity was observed in the adenocarcinoma component of six of 15 (40%) mixed adenocarcinoma-NECs. Mismatch repair deficiency, a mutant pattern of p53 expression and loss of Rb expression were observed in four (16%), 17 (68%) and nine (36%) cases, respectively, although these alterations were not associated with the PD-L1 CPS or other clinicopathological characteristics. CONCLUSIONS HER2 is unlikely to be an effective target in gastric NEC owing to the lack of HER2 expression, whereas the PD-1/PD-L1 pathway is a potential therapeutic target for gastric NEC because of the relatively high prevalence of a PD-L1 CPS of ≥ 1 in this subtype.
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Affiliation(s)
- Satoshi Yamashita
- Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.,Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroyuki Abe
- Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Akiko Kunita
- Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Kanthan R, Tharmaradinam S, Asif T, Ahmed S, Kanthan SC. Mixed epithelial endocrine neoplasms of the colon and rectum - An evolution over time: A systematic review. World J Gastroenterol 2020; 26:5181-5206. [PMID: 32982118 PMCID: PMC7495040 DOI: 10.3748/wjg.v26.i34.5181] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 06/18/2020] [Accepted: 08/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms ["mixed tumors colon" OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs). CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.
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Affiliation(s)
- Rani Kanthan
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon S7N 0W8, SK, Canada
| | - Suresh Tharmaradinam
- Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon S7N 0W8, SK, Canada
| | - Tehmina Asif
- Division of Oncology, Saskatoon Cancer Centre, Saskatoon S7N 0W8, SK, Canada
| | - Shahid Ahmed
- Division of Oncology, Saskatoon Cancer Centre, Saskatoon S7N 0W8, SK, Canada
| | - Selliah C Kanthan
- Division of General Surgery, University of Saskatchewan, Saskatoon S7N 0W8, SK, Canada
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Zheng M, Li T, Li Y, Zhang T, Zhang L, Ma W, Zhou L. Survival Profile and Prognostic Factors for Appendiceal Mixed Neuroendocrine Non-neuroendocrine Neoplasms: A SEER Population-Based Study. Front Oncol 2020; 10:1660. [PMID: 32903647 PMCID: PMC7438709 DOI: 10.3389/fonc.2020.01660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 07/28/2020] [Indexed: 12/17/2022] Open
Abstract
Introduction Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare form of neuroendocrine neoplasms (NENs). The purpose of this study was to investigate the characteristics and survival profile of appendiceal MiNENs, with a view of providing robust clinical features of this rare disease. Methods Patients were selected from the Surveillance, Epidemiology, and End Results database (2004–2016). The prognosis of MiNEN (n = 315) was compared with other histological subtypes including neuroendocrine tumor (NETs) (n = 1734), neuroendocrine carcinoma (NECs) (n = 375), goblet cell carcinoid (GCC) (n = 968), signet ring cell carcinoma (n = 463), mucinous adenocarcinoma (MAC) (n = 2355), and non-mucinous adenocarcinoma (NMAC) (n = 1187) in the appendix. Age-adjusted incidence was calculated using Joinpoint regression. The Cox proportional hazards model and the Fine–Gray competing risk model were used to perform overall survival (OS) and cancer-specific mortality (CSM) analyses, respectively. Results The age-adjusted incidence of MiNENs increased from 0.01/100,000 person-years in 2004 to 0.07/100,000 person-years in 2016. The 3-, 5-, and 10-year OS rates for MiNENs were 69.5, 57.4, and 43.7%, respectively, and the corresponding CSM rates were 23.1, 36.4, and 45.1%, respectively. Multivariate analysis revealed that the prognosis of MiNENs was worse than that of NETs, NECs, GCC, and MAC but better than that of NMAC and signet ring cell carcinoma. Tumor extension was the only independent factor influencing the prognosis of MiNENs, but tumor size, grade, and surgical approaches were not. Moreover, when compared with local excision or appendectomy, extensive surgery such as hemicolectomy or colectomy did not prolong the survival of individuals with MiNENs. Conclusion MiNEN is a rare but aggressive tumor with a poor prognosis differing from NENs, GCC and adenocarcinomas. To improve the prognosis of the disease, early diagnosis and comprehensive evaluation are necessary.
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Affiliation(s)
- Mengzhen Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tong Li
- Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Li
- Xinxiang Medical University, Xinxiang, China
| | - Tengfei Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lianfeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wang Ma
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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