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Yasuda K, Inokuchi S, Tsutsumi S, Takayama H, Ikebe M, Bandou T, Utsunomiya T, Urabe S. Long-term survival with complete remission after irinotecan plus cisplatin therapy for metachronous liver metastasis from a gastric mixed neuroendocrine-non-neuroendocrine neoplasm: a case report. Clin J Gastroenterol 2025:10.1007/s12328-025-02139-6. [PMID: 40310583 DOI: 10.1007/s12328-025-02139-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 04/17/2025] [Indexed: 05/02/2025]
Abstract
Gastric mixed neuroendocrine-non-neuroendocrine neoplasm, which consists of both exocrine and endocrine components, is rare and exhibits aggressive biological behavior and poor prognosis. A 64-year-old man underwent investigation for abdominal pain. An endoscopic examination revealed a 30-mm protruded lesion in the gastric antrum for which distal gastrectomy with lymph node dissection was performed. Histopathological examination showed two distinct components, an adenocarcinoma component and neuroendocrine carcinoma component, with immunohistochemical staining positive for CD56, chromogranin A, and synaptophysin. The final diagnosis was mixed neuroendocrine-non-neuroendocrine neoplasm, pT2, pN3, M0, stage IIIA. Multiple liver metastases were detected 3 months after surgery. The patient received irinotecan plus cisplatin therapy, which was effective, and the liver metastases disappeared. The patient remains alive, without any recurrence, more than 10 years after surgery. We present a rare case of gastric mixed neuroendocrine-non-neuroendocrine neoplasm and review the literature to contribute to improving our understanding of this kind of tumor.
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Affiliation(s)
- Kazuhiro Yasuda
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan.
| | - Shoichi Inokuchi
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Satoshi Tsutsumi
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Hiroomi Takayama
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Masahiko Ikebe
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Toshio Bandou
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Tohru Utsunomiya
- Department of Surgery, Oita Prefectural Hospital, 8-1 Bunyo, Oita, 870-8511, Japan
| | - Shogo Urabe
- Department of Pathology, Oita Prefectural Hospital, Oita, Japan
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Wang T, Cheng Y, Hu F, Wang Q. Residual gastric cancer with a mixed small cell neuroendocrine and keratinizing squamous cell carcinoma: A case report. World J Clin Oncol 2025; 16:102301. [PMID: 40130043 PMCID: PMC11866079 DOI: 10.5306/wjco.v16.i3.102301] [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: 10/14/2024] [Revised: 11/19/2024] [Accepted: 12/09/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Despite advancements in early detection and treatment, the prognosis and histological types for residual gastric cancer (GC) remains poor. CASE SUMMARY This case report presents a rare occurrence of residual GC featuring a combination of small cell neuroendocrine carcinoma (SCNEC) and squamous cell carcinoma (SCC) in a 60-year-old male patient. The patient, with a history of Billroth II gastrectomy for duodenal ulcer bleeding, presented with gastrointestinal bleeding. Preoperative computed tomography and positron emission tomography-computed tomography indicated adenocarcinoma with tumor and abdominal lymph node metastasis. The patient underwent laparoscopic total gastrectomy and lymph node dissection for residual GC. Histological examination of the resected tumor confirmed the presence of both SCNEC and SCC. Postoperatively, the patient underwent adjuvant chemotherapy four times. Two years later, the patient was found to occur esophageal cancer and was performed a small bowel stoma and radical esophagectomy. CONCLUSION In this case report, we detail a rare instance of residual GC with mixed SCNEC and SCC, emphasizing the complexity of diagnosis and treatment, and the need for ongoing research.
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Affiliation(s)
- Tian Wang
- Department of Gastroenterology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, Jiangxi Province, China
| | - Yang Cheng
- Department of Pathology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, Jiangxi Province, China
| | - Fan Hu
- Department of Pathology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, Jiangxi Province, China
| | - Qiang Wang
- Department of Gastroenterology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, Jiangxi Province, China
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Kwak Y, Nam SK, Park Y, Suh YS, Ahn SH, Kong SH, Park DJ, Lee HJ, Kim HH, Yang HK, Lee HS. Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma. Mod Pathol 2024; 37:100568. [PMID: 39029904 DOI: 10.1016/j.modpat.2024.100568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 06/30/2024] [Accepted: 07/11/2024] [Indexed: 07/21/2024]
Abstract
This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies.
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Affiliation(s)
- Yoonjin Kwak
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Soo Kyung Nam
- Department of Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Korea
| | - Yujun Park
- Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk-Joon Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Ho Kim
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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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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Matsueda K, Uedo N, Kitamura M, Shichijo S, Maekawa A, Kanesaka T, Takeuchi Y, Higashino K, Ishihara R, Michida T, Kawano S, Kawahara Y. Endoscopic features of gastric neuroendocrine carcinoma. J Gastroenterol Hepatol 2023; 38:1808-1817. [PMID: 37527834 DOI: 10.1111/jgh.16309] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 08/03/2023]
Abstract
BACKGROUND AND AIM The endoscopic features of gastric neuroendocrine carcinoma (G-NEC) have not been clarified; therefore, they were investigated in relation to clinicopathological findings. METHODS Consecutive patients with G-NECs who had undergone endoscopic or surgical resection at our institution between January 2005 and March 2022 were included in this retrospective study. The endoscopic and clinicopathological findings of the lesions were analyzed to provide information of diagnostic value. In addition, cases of gastric neuroendocrine tumor (G-NET) and common-type gastric adenocarcinoma treated in the same study period were identified to compare the endoscopic findings between each G-NEC versus G-NET, and G-NEC versus common-type gastric adenocarcinoma. Patients with common-type gastric adenocarcinoma were matched for age, sex, tumor size, and depth of tumor invasion in 1:3 ratio. RESULTS Among 15 patients with 15 G-NECs, submucosal tumor-like marginal elevation (87%), adherent white coat (67%), and ulceration with a distinct border (60%) were characteristic endoscopic findings in white-light images. Magnifying narrow-band imaging endoscopy revealed an absent microsurface (MS) pattern plus disrupted irregular microvessel (MV) in five (71%) of seven cases with evaluable MS and MV patterns. The area with an absent MS pattern plus disrupted irregular MV corresponded to the histological finding of NEC component in all five cases. These endoscopic features were all significantly more frequent in G-NECs than G-NETs (n = 22) or common-type gastric adenocarcinomas (n = 45). CONCLUSIONS These endoscopic features should be taken into consideration to increase the index of suspicion and to improve the accuracy of target biopsies for G-NEC.
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Affiliation(s)
- Katsunori Matsueda
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
- Department of Gastroenterology, Okayama University Hospital, Okayama, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Masanori Kitamura
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Satoki Shichijo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Akira Maekawa
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Kanesaka
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Koji Higashino
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tomoki Michida
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Seiji Kawano
- Department of Gastroenterology, Okayama University Hospital, Okayama, Japan
| | - Yoshiro Kawahara
- Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Ikegame K, Hatakeyama K, Terashima M, Sugino T, Aizawa D, Furukawa K, Fujiya K, Tanizawa Y, Bando E, Yamaguchi K. Molecular profiling of gastric neuroendocrine carcinomas. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106987. [PMID: 37463826 DOI: 10.1016/j.ejso.2023.106987] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 06/05/2023] [Accepted: 07/11/2023] [Indexed: 07/20/2023]
Abstract
Gastric neuroendocrine carcinoma (G-NEC) usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because common pathogenic mutations are shared. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis. We aimed to elucidate the tumorigenesis of G-NEC by focusing on the proportion of NEC components. Thirteen patients with G-NEC were included in this study. Comprehensive genetic analysis using whole-exome sequencing was performed. G-NEC without an adenocarcinoma component was defined as pure NEC. TP53 was detected as the most frequent gene mutation (85% of the patients), independent of classification. RB1, KMT2C, LTBP1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Pure NEC has different somatic mutation profile than other NECs. This study provides insights into the mechanism of tumorigenesis in G-NEC.
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Affiliation(s)
- Ko Ikegame
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Keiichi Hatakeyama
- Cancer Multiomics Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Daisuke Aizawa
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Kenichiro Furukawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Keiichi Fujiya
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Yutaka Tanizawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Etsuro Bando
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Ken Yamaguchi
- Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
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Early gastric mixed neuroendocrine–non-neuroendocrine neoplasms with endoscopic findings of neuroendocrine cell carcinoma components exposed on the mucosal surface: a case report. J Med Case Rep 2022; 16:416. [PMID: 36372896 PMCID: PMC9661742 DOI: 10.1186/s13256-022-03657-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/24/2022] [Indexed: 11/15/2022] Open
Abstract
Background Gastric mixed neuroendocrine–non-neuroendocrine neoplasms are rare malignant tumors. The lack of specific findings makes it difficult to diagnose endoscopically. We report the case of early gastric mixed neuroendocrine–non-neuroendocrine neoplasms treated by endoscopic submucosal dissection. Case presentation An 81-year-old Japanese female underwent esophagogastroduodenoscopy for screening and was treated with endoscopic submucosal dissection for the diagnosis of early gastric cancer. Histopathologically, the lesion was diagnosed as mixed neuroendocrine–non-neuroendocrine neoplasms (tubular adenocarcinoma 2 60%, endocrine cell carcinoma 40%), pT1b(submucosa (SM) 900 μm), pUL(−), Ly(+), v(−), pHM0, pVM0. After additional surgical resection without adjuvant chemotherapy, she has had no recurrences or metastases for 3 years. Conclusions Comparing narrow-band imaging magnified endoscopic findings with pathological findings, the depressed area with a lack of surface structure was consistent with the neuroendocrine cell carcinoma component, while narrow-band imaging magnification findings showed non-network vessels. In this case, we examined endoscopic findings of early stage mixed neuroendocrine—non-neuroendocrine neoplasms in detail and compared it with the pathological findings. We believe that these endoscopic findings contribute to the diagnosis of mixed neuroendocrine–non-neuroendocrine neoplasms and can lead to its early detection.
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Cai XC, Wu SD. Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review. World J Clin Cases 2022; 10:8212-8223. [PMID: 36159526 PMCID: PMC9403678 DOI: 10.12998/wjcc.v10.i23.8212] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/21/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored.
AIM To review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database.
METHODS Data of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)".
RESULTS The GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006–1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839–5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC.
CONCLUSION The clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.
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Affiliation(s)
- Xing-Chen Cai
- Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China
| | - Sheng-Dong Wu
- Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China
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Li ZF, Lu HZ, Chen YT, Bai XF, Wang TB, Fei H, Zhao DB. Mixed large and small cell neuroendocrine carcinoma of the stomach: A case report and review of literature. World J Clin Cases 2022; 10:5502-5509. [PMID: 35812663 PMCID: PMC9210888 DOI: 10.12998/wjcc.v10.i16.5502] [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: 12/27/2021] [Revised: 02/18/2022] [Accepted: 04/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric neuroendocrine carcinoma (GNEC) is a rare histological subtype of gastric cancer, which is categorized into small cell and large cell neuroendocrine carcinomas. It is characterized by strong invasiveness and poor prognosis. Mixed large and small cell neuroendocrine carcinoma (L/SCNEC) is an extremely rare pathological type of gastric cancer, and there have been no reports on this situation until now.
CASE SUMMARY Herein, we first present a 57-year-old patient diagnosed with L/SCNEC of the stomach. A 57-year-old Chinese male presented with epigastric discomfort. Outpatient gastroscopic biopsy was performed, and pathological examination revealed that the cardia was invaded by adenocarcinoma. The patient underwent laparoscopic-assisted radical proximal subtotal gastrectomy and was diagnosed with L/SCNEC. He refused adjuvant treatment and was followed up every 3 mo. Eight months after the operation, the patient showed no evidence of local recurrence or distant metastasis.
CONCLUSION We advocate conducting further genomic studies to explore the origin of gastric large cell and small cell neuroendocrine carcinoma and using different chemotherapy schemes according to large or small cell neuroendocrine carcinoma of the stomach for clinical research to clarify the heterogeneity of GNEC and improve the prognosis of patients with GNEC.
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Affiliation(s)
- Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hai-Zhen Lu
- Department of Pathology, National Cancer Center/National Clinical Research 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 for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao-Feng Bai
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tong-Bo Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research 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 for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Iwasaki K, Barroga E, Enomoto M, Tsurui K, Shimoda Y, Matsumoto M, Miyoshi K, Ota Y, Matsubayashi J, Nagakawa Y. Long-term surgical outcomes of gastric neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasms. World J Surg Oncol 2022; 20:165. [PMID: 35610656 PMCID: PMC9131531 DOI: 10.1186/s12957-022-02625-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/06/2022] [Indexed: 11/25/2022] Open
Abstract
Background Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital. Methods We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN. Results The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62–84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0–95)%, and the mean mitotic score was 107.9 (0–400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0–129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408–0.912). Conclusion The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis.
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Affiliation(s)
- Kenichi Iwasaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
| | - Edward Barroga
- Graduate School of Nursing Science, St. Luke's International University, Tokyo, Japan
| | - Masaya Enomoto
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Kazushige Tsurui
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Yota Shimoda
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Moe Matsumoto
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Kenta Miyoshi
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Yoshihiro Ota
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Jun Matsubayashi
- Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
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11
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Tomita Y, Seki H, Matsuzono E, Kobayashi Y, Sogabe S, Sugai N, Fujita J, Suzuki A. Early gastric mixed neuroendocrine‐non‐neuroendocrine neoplasm with early poor prognosis after endoscopic submucosal dissection: A case report. DEN OPEN 2022; 2:e10. [PMID: 35310728 PMCID: PMC8828207 DOI: 10.1002/deo2.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 11/12/2022]
Abstract
Early gastric mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNENs) are rare diseases, with no data on their incidence and prognosis. We report the case of intramucosal gastric MiNENs for endoscopic submucosal dissection (ESD) treatment. An 80‐year‐old male underwent esophagogastroduodenoscopy for screening and was suspected of early gastric cancer type 0‐IIa+IIc on the lesser curvature of the antrum, for which ESD treatment was performed. Histopathologically, the diagnosis was MiNENs. Synaptophysin‐positive adenoductal structures were observed in the adenocarcinoma component, suggesting that adenocarcinoma had dedifferentiated into neuroendocrine carcinoma. The tumor was located within the mucosal layer, with lympho‐vascular invasion. The patient was kept under observation; however, 6 months after the ESD, computed tomography scan revealed prominent ascites, enlarged lymph nodes, and liver metastases, and MiNENs were suspected to have poor prognosis. If MiNENs diagnosis is made preoperatively or postoperatively, surgical resection may be considered as treatment regardless of the tumor depth or lympho‐vascular invasion.
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Affiliation(s)
- Yusuke Tomita
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | - Hideyuki Seki
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | - Emi Matsuzono
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | | | - Susumu Sogabe
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | - Nozomu Sugai
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | - Jun Fujita
- Department of Gastroenterology KKR Sapporo Medical Center Hokkaido Japan
| | - Akira Suzuki
- Department of Pathology KKR Sapporo Medical Center Hokkaido Japan
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12
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Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: A review. World J Clin Cases 2021; 9:7973-7985. [PMID: 34621854 PMCID: PMC8462212 DOI: 10.12998/wjcc.v9.i27.7973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
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Affiliation(s)
- Hüseyin Köseoğlu
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| | - Tolga Duzenli
- Department of Gastroenterology, Hitit University Erol Olçok Education and Research Hospital, Çorum 19200, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
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13
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Alawad M, Gupta R, Haseeb MA, Brunicardi FC. Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder. Gastroenterology Res 2020; 13:269-278. [PMID: 33447306 PMCID: PMC7781272 DOI: 10.14740/gr1323] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/23/2020] [Indexed: 12/17/2022] Open
Abstract
Neuroendocrine neoplasms of the gallbladder are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. These neoplasms can also be found along with other malignant neoplasms of epithelial origin, mostly adenocarcinomas. Herein, we describe an unusual finding of a three-component mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) of the gallbladder. We also review the literature on 29 similar cases and summarize key features. We report on a 62-year-old woman who presented with right upper quadrant pain with a positive Murphy’s sign. A clinical diagnosis of neoplasia was entertained and she underwent cholecystectomy. Gross examination of the specimen revealed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma, an adjacent neuroendocrine carcinoma (each of these two components composed more than 30% of the neoplasm), and a superficial adenocarcinoma (composing 10% of the neoplasm). Gallbladder MiNENs present with similar symptoms and in the same age group as do carcinomas; however, their prognosis is often poor. Specific management and treatment guidelines have not been established since MiNENs are very rare.
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Affiliation(s)
- Mouyed Alawad
- Department of Pathology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Raavi Gupta
- Department of Pathology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA.,Department of Cell Biology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - M A Haseeb
- Department of Pathology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA.,Department of Cell Biology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - F Charles Brunicardi
- Department of Surgery, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
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14
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Abstract
An 80-year-old woman presented with a 30-mm protruding lesion-like submucosal tumor with a central depression located at the anterior wall of the upper gastric body. The depressed area had a well-demarcated margin, while the other area was covered by a non-neoplastic mucosa. A biopsy specimen revealed neuroendocrine carcinoma. Endoscopic ultrasonography revealed a heterogeneous mass with a clearly distinguished border in the submucosal layer. The mass had two distinct areas adjacent to each other. In addition, a hypoechoic zone was observed on the margin of the mass. Distal gastrectomy was performed. The final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm arising from the heterotopic gastric gland.
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Affiliation(s)
- Yasuyuki Tanaka
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Yumi Tokubayashi
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Shigehiko Fujii
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Toshihiro Kusaka
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | | | - Hiroyuki Kokuryu
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
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15
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Qin Y, Jiang S, Liu P, Yang J, Yang S, He X, Zhou S, Gui L, Lin J, Du X, Yi Y, Sun Y, Shi Y. Characteristics and Management of TP53-Mutated Diffuse Large B-Cell Lymphoma Patients. Cancer Manag Res 2020; 12:11515-11522. [PMID: 33204162 PMCID: PMC7666999 DOI: 10.2147/cmar.s269624] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 09/08/2020] [Indexed: 01/21/2023] Open
Abstract
Background/Aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP–like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53mut DLBCL patients compared to R-CHOP–only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.
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Affiliation(s)
- Yan Qin
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Shiyu Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Peng Liu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Jianliang Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Sheng Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Xiaohui He
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Shengyu Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Lin Gui
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Jing Lin
- Burning Rock Biotech, Guangzhou, Mainland China
| | - Xinhua Du
- Geneplus Beijing, Beijing, People's Republic of China
| | - Yuting Yi
- Geneplus Beijing, Beijing, People's Republic of China
| | - Yan Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
| | - Yuankai Shi
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People's Republic of China
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16
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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: 6] [Impact Index Per Article: 1.2] [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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17
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Koh J, Nam SK, Kwak Y, Kim G, Kim KK, Lee BC, Ahn SH, Park DJ, Kim HH, Park KU, Kim WH, Lee HS. Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas. J Pathol 2020; 253:94-105. [PMID: 32985687 DOI: 10.1002/path.5556] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 09/05/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022]
Abstract
We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients - 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs - and 21 matched non-neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components. TP53 was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). All TP53 mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset of TP53WT MANECs had a microsatellite-unstable phenotype or amplifications in various oncogenes including ERBB2 and NMYC, and the only TP53WT pure NEC harbored MYC amplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequent RB1 mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Jiwon Koh
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Soo Kyung Nam
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Yoonjin Kwak
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Gilhyang Kim
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | | | | | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Kyoung Un Park
- Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Woo Ho Kim
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.,Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
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18
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Hirose S, Hasegawa N, Kawai H, Yamaura M, Mizui T, Komatsu Y, Nagase M, Sato M, Hattori J, Endo M, Yamamoto Y, Ishige K, Fukuda K, Hyodo I, Mizokami Y. Mediastinal Neuroendocrine Carcinoma Slowly Growing for 8 Years after Surgical Resection of Esophageal Squamous Cell Carcinoma. Intern Med 2020; 59:2505-2509. [PMID: 32641665 PMCID: PMC7662036 DOI: 10.2169/internalmedicine.4584-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 70-year-old woman was referred to our department due to a solitary mediastinal tumor which gradually grew near the site of anastomosis for 8 years after radical surgery of esophageal squamous cell carcinoma. It was difficult to distinguish the lymph node recurrence of esophageal cancer from another tumor of unknown primary origin. Endoscopic ultrasound-guided fine-needle aspiration was performed, and the tumor was diagnosed to be neuroendocrine carcinoma. She received concurrent chemoradiotherapy with etoposide plus cisplatin. After the completion of chemoradiotherapy, the tumor disappeared. A solitary growing tumor which develops after radical resection of cancer would be better to be examined histologically in order to make an accurate diagnosis and select the most appropriate treatment.
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Affiliation(s)
- Suguru Hirose
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Naoyuki Hasegawa
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Hitomi Kawai
- Department of Pathology, University of Tsukuba Hospital, Japan
| | - Masamichi Yamaura
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Tsuneo Mizui
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Yoshiki Komatsu
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Masaomi Nagase
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Masashi Sato
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Junji Hattori
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Masato Endo
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Yoshiyuki Yamamoto
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Kazunori Ishige
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Kuniaki Fukuda
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Ichinosuke Hyodo
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
| | - Yuji Mizokami
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Japan
- Endoscopic Center, University of Tsukuba Hospital, Japan
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19
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Neuroendocrine carcinoma arising from Barrett's esophageal adenocarcinoma: a case report. Clin J Gastroenterol 2020; 13:1028-1035. [PMID: 32852724 DOI: 10.1007/s12328-020-01210-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/12/2020] [Indexed: 12/12/2022]
Abstract
Neuroendocrine carcinoma in Barrett's esophagus is rare and its developmental mechanisms remain unclear. Neuroendocrine carcinoma arising in Barrett's esophagus with adenocarcinoma was detected at an early stage and resected by endoscopic submucosal dissection. Detailed pathological examination revealed that the neuroendocrine carcinoma originated via differentiation of the preexisting adenocarcinoma. A 79-year-old man presented with a flat protruding lesion in the esophagogastric junction. Esophagogastroduodenoscopy revealed a red flat 10-mm protruding lesion in the Barrett's epithelium and a shallow depression at the distal end. Narrow band imaging with magnification showed that the blood vessels in the protrusion were dilated and meandered irregularly, while those in the depression were small and did not form a network; the blood vessels were missing in some parts of the depression. Well-differentiated adenocarcinoma was diagnosed after analysis of the biopsy specimen of the protrusion, and endoscopic submucosal dissection was performed. The pathological diagnosis was neuroendocrine carcinoma with an adenocarcinoma component.
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20
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Chen J, Wang A, Ji K, Bu Z, Ji J. Comparison of overall survival of gastric neoplasms containing neuroendocrine carcinoma components with gastric adenocarcinoma: a propensity score matching study. BMC Cancer 2020; 20:777. [PMID: 32811471 PMCID: PMC7437076 DOI: 10.1186/s12885-020-07281-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/09/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Gastric neoplasms containing neuroendocrine carcinoma (NEC) components are rare malignancies with highly aggressive behavior and a poor prognosis and include pure NEC and mixed tumors containing NEC components. We aimed to investigate whether there is a distinct difference in overall survival (OS) between gastric neoplasms containing NEC components and gastric adenocarcinoma. METHODS Surgically resected gastric neoplasms containing NEC components (n = 180) and gastric adenocarcinomas (n = 785) from January 2013 to December 2019 at Peking University Cancer Hospital were retrospectively analysed. Patients were categorized into a surgical group and a neoadjuvant group and adjusted using propensity score matching. In the two groups, gastric neoplasms containing NEC components were divided into pure NEC and mixed tumors with less than 30% (< 30% G-HMiNEN), between 30 and 70% (G-HMiNEN) and more than 70% (> 70% G-HMiNEN) neuroendocrine carcinoma components. OS was compared between these groups and the gastric adenocarcinoma group. RESULTS The OS of gastric neoplasms containing neuroendocrine NEC components was poorer than that of gastric adenocarcinomas in the surgical group, regardless of whether the percentage of neuroendocrine cancer components was less than 30%, between 30 and 70%, more than 70% or 100%. Cox multivariable regression analysis suggested that tumor category (neoplasms containing NEC components or gastric adenocarcinoma) was an independent risk factor for prognosis. Interestingly, among patients receiving neoadjuvant therapy, the difference was not significant. CONCLUSIONS Gastric neoplasms containing any proportion of NEC components had poorer overall survival than gastric adenocarcinoma in patients treated with surgery directly, indicating that these neoplasms are more malignant than gastric adenocarcinoma. Among the patients receiving neoadjuvant therapy, the difference in overall survival was not significant, which was in sharp contrast with the results of the surgery group, suggesting that neoadjuvant therapy may have a good effect in the treatment of these neoplasms.
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Affiliation(s)
- Jiahui Chen
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Anqiang Wang
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Ke Ji
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Zhaode Bu
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Jiafu Ji
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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21
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Jiao X, Wang Z, Peng X, Zhang L, Zhou L. Effects of tumor types on treatment strategy formulation and prognostic evaluation of gastric neuroendocrine tumors. Future Oncol 2020; 16:2197-2207. [PMID: 32687408 DOI: 10.2217/fon-2020-0150] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Aim: The effects of different types of gastric neuroendocrine tumors (G-NETs) on treatment strategy formulation and prognostic evaluation still remain controversial due to their rarity. Methods: 187 patients diagnosed with G-NETs were subdivided into four types based on the pathophysiology, etiology and presentation. Results: Type I, II G-NETs >1.0 cm and type III, IV G-NETs >2.0 cm are proved with aggressive behavior (p < 0.05). Type III G-NETs with higher Ki-67 index and tumor stage showed more invasive potential than type I and II G-NETs (p < 0.05). Endoscopic resection is the primary treatment for type I, II G-NETs, while surgical combined with chemotherapy is associated with favorable outcomes for type IV G-NETs. Conclusion: The clinical classifications of G-NETs are of great significance for the choice of treatment and the evaluation of prognosis.
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Affiliation(s)
- Xiaoxiao Jiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Zhaodi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Xiaoqian Peng
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Lianfeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
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Bocchini M, Nicolini F, Severi S, Bongiovanni A, Ibrahim T, Simonetti G, Grassi I, Mazza M. Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management-An Updated Review. Front Oncol 2020; 10:831. [PMID: 32537434 PMCID: PMC7267066 DOI: 10.3389/fonc.2020.00831] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 04/28/2020] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PanNENs) are rare sporadic cancers or develop as part of hereditary syndromes. PanNENs can be both functioning and non-functioning based on whether they produce bioactive peptides. Some PanNENs are well differentiated while others-poorly. Symptoms, thus, depend on both oncological and hormonal causes. PanNEN diagnosis and treatment benefit from and in some instances are guided by biomarker monitoring. However, plasmatic monoanalytes are only suggestive of PanNEN pathological status and their positivity is typically followed by deepen diagnostic analyses through imaging techniques. There is a strong need for new biomarkers and follow-up modalities aimed to improve the outcome of PanNEN patients. Liquid biopsy follow-up, i.e., sequential analysis on tumor biomarkers in body fluids offers a great potential, that need to be substantiated by additional studies focusing on the specific markers and the timing of the analyses. This review provides the most updated panorama on PanNEN biomarkers.
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Affiliation(s)
- Martine Bocchini
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Fabio Nicolini
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Stefano Severi
- Nuclear Medicine and Radiometabolic Units, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alberto Bongiovanni
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Toni Ibrahim
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giorgia Simonetti
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Ilaria Grassi
- Nuclear Medicine and Radiometabolic Units, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Massimiliano Mazza
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
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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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Boons G, Vandamme T, Peeters M, Van Camp G, Op de Beeck K. Clinical applications of (epi)genetics in gastroenteropancreatic neuroendocrine neoplasms: Moving towards liquid biopsies. Rev Endocr Metab Disord 2019; 20:333-351. [PMID: 31368038 DOI: 10.1007/s11154-019-09508-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
High-throughput analysis, including next-generation sequencing and microarrays, have strongly improved our understanding of cancer biology. However, genomic data on rare cancer types, such as neuroendocrine neoplasms, has been lagging behind. Neuroendocrine neoplasms (NENs) develop from endocrine cells spread throughout the body and are highly heterogeneous in biological behavior. In this challenging disease, there is an urgent need for new therapies and new diagnostic, prognostic, follow-up and predictive biomarkers to aid patient management. The last decade, molecular data on neuroendocrine neoplasms of the gastrointestinal tract and pancreas, termed gastroenteropancreatic NENs (GEP-NENs), has strongly expanded. The aim of this review is to give an overview of the recent advances on (epi)genetic level and highlight their clinical applications to address the current needs in GEP-NENs. We illustrate how molecular alterations can be and are being used as therapeutic targets, how mutations in DAXX/ATRX and copy number variations could be used as prognostic biomarkers, how far we are in identifying predictive biomarkers and how genetics can contribute to GEP-NEN classification. Finally, we discuss recent studies on liquid biopsies in the field of GEP-NENs and illustrate how liquid biopsies can play a role in patient management. In conclusion, molecular studies have suggested multiple potential biomarkers, but further validation is ongoing.
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Affiliation(s)
- Gitta Boons
- Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650, Edegem, Belgium
| | - Timon Vandamme
- Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650, Edegem, Belgium
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE, Rotterdam, The Netherlands
| | - Marc Peeters
- Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium
| | - Guy Van Camp
- Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium.
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650, Edegem, Belgium.
| | - Ken Op de Beeck
- Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610, Wilrijk, Belgium
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650, Edegem, Belgium
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Zhu X, Jing H, Yao T. Clinical characteristics of early neuroendocrine carcinoma in stomach: A case report and review of literature. Medicine (Baltimore) 2019; 98:e16638. [PMID: 31348317 PMCID: PMC6709248 DOI: 10.1097/md.0000000000016638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Gastric neuroendocrine carcinoma (NEC) is rare. It is considered to be aggressive and has a poor prognosis since the diagnosis is usually made at its advanced stage. However, the survival rate is increased in some early gastric NECs. This study showed a case and reviewed the clinical characteristics of early NECs in stomach. PATIENT CONCERNS A 38-year-old man displayed no symptoms and underwent the gastric endoscopy test for his health examination, which showed a red slightly depressed lesion 1.0 cm in size on the lesser curvature of gastric cardia. Magnifying endoscopy with narrow-band imaging (NBI) revealed a clear demarcation and an irregular mesh in vessels within the depressed area. The background mucosa was negative for atrophic gastritis and Helicobacter Pylori infection. A contrast-enhanced computed tomography (CT) scan disclosed no obvious thickening of stomach and lymphadenopathy. Blood tests and physical examination were unremarkable. He had not received any surgical treatment and denied a family history of cancer and any genetic disorders. The pathologic result of biopsy from the lesion was suspicious of superficial carcinoma. Then endoscopic submucosal dissection (ESD) was performed. DIAGNOSIS Gastric NEC G3 in the early stage (T1aN0M0). INTERVENTIONS Concerning this patient's situation, we considered the ESD as a curable treatment. And no radical surgery or adjuvant chemotherapy was arranged. OUTCOMES The patient is doing well and displays no recurrence for 11 months, who is still in follow-up. LESSONS SUBSECTIONS AS PER STYLE The early diagnosis and effective treatment by endoscopy would contribute to improve the prognosis of gastric NECs.
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Affiliation(s)
| | - Haiyan Jing
- Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China
| | - Takashi Yao
- Department of Human Pathology, Juntendo University, Tokyo 113-8421, Japan
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Mafficini A, Scarpa A. Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms. Endocr Rev 2019; 40:506-536. [PMID: 30657883 PMCID: PMC6534496 DOI: 10.1210/er.2018-00160] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Accepted: 12/27/2018] [Indexed: 12/11/2022]
Abstract
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are heterogeneous regarding site of origin, biological behavior, and malignant potential. There has been a rapid increase in data publication during the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal neuroendocrine tumors (NETs). This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NENs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways, including DNA damage repair, cell cycle regulation, and phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also owing to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification, and planning of personalized therapy.
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Affiliation(s)
- Andrea Mafficini
- ARC-Net Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.,Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- ARC-Net Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.,Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
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27
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The Significant Influence of the Neuroendocrine Component on the Survival of Patients with Gastric Carcinoma Characterized by Coexisting Exocrine and Neuroendocrine Components. JOURNAL OF ONCOLOGY 2019; 2019:3671268. [PMID: 30992704 PMCID: PMC6434268 DOI: 10.1155/2019/3671268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 01/30/2019] [Accepted: 02/18/2019] [Indexed: 12/14/2022]
Abstract
Background Gastric adenocarcinoma patients with a neuroendocrine (NE) component are frequently observed in routine practice. Several previous studies have investigated the influence of a NE component on the survival of these patients; however, the results were inconsistent. Methods We retrospectively investigated a consecutive series of 95 gastric adenocarcinoma patients with a NE component and 190 gastric adenocarcinoma patients without a NE component. We adopted 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% as the cut-off proportions of the NE component, respectively, and analyzed the patients' overall survival according to the proportion of the NE component. Results The 1-, 3-, and 5-year actual survival rates of the patients with a NE component were 90.1%, 72.3%, and 67.2%, respectively, and for those without a NE component 94.2%, 79.3%, and 75.7%, respectively. The multivariate analysis showed that the patients with NE components >70% (HR: 2.156; 95% CI: 1.011, 4.597; p=0.047) and >90% (HR: 2.476; 95% CI: 1.088, 5.634; p=0.031) had significantly worse survival than those without a NE component. Only the diameter of tumors (>4.64 cm) (HR: 2.585; 95% CI: 1.112, 6.006; p=0.027) and pN3 (HR: 2.953; 95% CI: 1.051, 8.293; p=0.040) were independently associated with worse overall survival for gastric adenocarcinoma patients with a NE component (all p<0.05). Conclusion Gastric adenocarcinoma patients with a NE component >70% and >90% have significantly worse survival than those without a NE component. Only the diameter of tumors and the number of metastatic lymph nodes are independent prognostic factors for gastric adenocarcinoma patients with a NE component.
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Gastric Endocrine Carcinoma: A New Look at a Rare Tumor From Cases in Japan. Int Surg 2019. [DOI: 10.9738/intsurg-d-19-00015.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective:
We evaluated the clinicopathologic factors associated with gastric neuroendocrine carcinoma (NEC) in patients who underwent surgical resection. Gastric NEC is rare, accounting for only about 0.6% of all malignant gastric tumors. Neither its pathogenesis nor its treatment has been fully established.
Methods:
We assessed 10 patients with gastric NEC who underwent surgical resection in our hospital between September 2007 and June 2019.
Results:
The patients consisted of 9 men and 1 woman, aged 63 to 78 years. The tumors were localized in the upper region (n = 5), middle region (n = 3), and lower region (n = 2). The macroscopic types were evaluated as 0-IIc (n = 3), 1 (n = 3), 2 (n = 1), 3 (n = 2), and 4 (n = 1). The stages were ascertained as IA (n = 3), IIB (n = 3), IIIA (n = 2), IIIB (n = 1), and IIIC (n = 1). Radical resection was performed in all the patients. After surgery, relapse-free survival was achieved in 6 patients. The mean postoperative survival time was 63.5 months. On immunostaining, 6 patients were positive for CD56, and all were positive synaptophysin and chromogranin A. Of the 10 patients, standard-type adenocarcinoma was concomitantly present in 6.
Conclusions:
Some patients with surgically resected gastric NEC survived over a long period, suggesting the usefulness of radical resection. In future studies, the pathogenesis of gastric NEC should be fully clarified, and therapeutic strategies must be further developed.
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29
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Yan B, Cui M, You J, Li F, Liu H. Gastric adenocarcinoma is concurrent with metastatic neuroendocrine cancer treated with nivolumab and chemotherapy: A case report. Mol Clin Oncol 2018; 9:607-612. [PMID: 30546888 PMCID: PMC6256192 DOI: 10.3892/mco.2018.1740] [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: 06/28/2018] [Accepted: 09/21/2018] [Indexed: 11/23/2022] Open
Abstract
Gastric adenocarcinoma concurrent with metastatic neuroendocrine cancer (NEC) is rare. In the present case report, a 39-year-old male was first pathologically diagnosed by gastric endoscopy as having a highly differentiated adenocarcinoma. Next, positron emission tomography-computed tomography examination and bone marrow biopsy confirmed extensive metastasis. Subsequently, the patient underwent 6 cycles of immunotherapy (nivolumab, 160 mg) and 5 cycles of chemotherapy based on the XELOX regimen (oxaliplatin + capecitabine). Following this, the patient received the final cycles of nivolumab and XELOX; however, the patient then succumbed. Further biopsy of the metastatic collarbone lymph nodes indicated NEC. Overall, the progression-free survival was ~3.5 months, and overall survival (OS) was ~6 months. The case presented the possibility of concurrent gastric adenocarcinoma and NEC in the clinic. In addition, the efficacy of a combined regimen such as immunotherapy and chemotherapy for such disorders still requires further validation in the future.
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Affiliation(s)
- Bing Yan
- Department of Oncology, Hainan Branch of PLA General Hospital, Sanya, Hainan 572000, P.R. China
| | - Meiqi Cui
- Department of Outpatient, Hainan Branch of PLA General Hospital, Sanya, Hainan 572000, P.R. China
| | - Junhao You
- Department of Oncology, Hainan Branch of PLA General Hospital, Sanya, Hainan 572000, P.R. China
| | - Fang Li
- Department of Oncology, Hainan Branch of PLA General Hospital, Sanya, Hainan 572000, P.R. China
| | - Hui Liu
- Department of Oncology, Hainan Branch of PLA General Hospital, Sanya, Hainan 572000, P.R. China
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Ochiai T, Ominami M, Nagami Y, Fukunaga S, Toyokawa T, Yamagami H, Tanigawa T, Watanabe T, Ohira M, Ohsawa M, Fujiwara Y. Lymph Node Metastasis of Mixed Adenoneuroendocrine Carcinoma after Curative Resection Using the Expanded Criteria for Early Gastric Cancer. Intern Med 2018; 57:2837-2842. [PMID: 29780112 PMCID: PMC6207817 DOI: 10.2169/internalmedicine.0311-17] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Endoscopic submucosal dissection (ESD) of lesions using expanded indications for early gastric cancer (EGC) has been accepted as an alternative treatment for cases without lymph node metastasis. We herein report a rare case of metastatic lymph node tissue in mixed adenoneuroendocrine carcinoma (MANEC) after curative ESD using the expanded pathological criteria. A 70-year-old man underwent ESD for two EGC lesions. A pathological examination revealed lesions that required curative resection based on the expanded pathological criteria of the Japanese classification of gastric carcinoma. However, lymph node metastasis was detected at 26 months after ESD. Additional surgical resection was performed and MANEC was pathologically diagnosed in the metastatic lymph node. The patient subsequently underwent additional chemotherapy and remains alive at 2 years after surgery. Even though MANEC is a rare tumor, this case suggests that periodic follow-up is important when patients undergo curative resection by ESD based on the expanded indications because of the high malignant potential and the poor prognosis.
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Affiliation(s)
- Tadashi Ochiai
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Masaki Ominami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Shusei Fukunaga
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Takahiro Toyokawa
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
| | - Masaichi Ohira
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Japan
| | - Masahiko Ohsawa
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan
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Mixed adenoneuroendocrine carcinoma of the esophagogastric junction: a case report. Surg Case Rep 2018; 4:56. [PMID: 29900476 PMCID: PMC5999592 DOI: 10.1186/s40792-018-0464-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 06/04/2018] [Indexed: 01/05/2023] Open
Abstract
Background Mixed adenoneuroendocrine carcinoma (MANEC) is a tumor of the gastrointestinal tract that contains both exocrine and endocrine components, with each component exceeding 30% of the total tumor area. Because MANECs are exceedingly rare, no therapeutic strategies have been established yet. Case presentation An 81-year-old man was referred to our hospital with a 5-month history of dysphagia. Esophagogastroduodenoscopy revealed an ulcerated mass in the lower thoracic esophagus, extending up to the esophagogastric junction (33 to 40 cm from the incisors). The initial biopsy diagnosis was adenocarcinoma. Computed tomography revealed no evidence of lymph node or distant metastasis. The patient was treated by thoracoscopic esophagectomy with three-field lymph node dissection and gastric tube reconstruction via a posterior mediastinal approach, under the diagnosis of esophagogastric junctional cancer (T3N0M0, stage IIA). Histopathological examination revealed two distinct components, namely, a neuroendocrine carcinoma component and an adenocarcinoma component, and the patient was diagnosed as having mixed adenoneuroendocrine carcinoma (MANEC). He presented with liver metastasis 6 months after the surgery. Thereafter, the tumor became even more aggressive, and the patient died 8 months after the surgery. Conclusions We report a patient with MANEC of the esophagogastric junction. Close attention should be paid to such patients, as MANEC can be a highly aggressive tumor, showing rapid progression. In the treatment of MANEC, it is necessary to carefully consider the pathological features in each individual case.
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Kusunoki R, Fujishiro H, Onoda Y, Suemitsu S, Fujiwara A, Tsukano K, Kotani S, Kuroki D, Ogawa S, Yamanouchi S, Aimi M, Ito S, Miyaoka Y, Miyake T, Kohge N, Imaoka T, Takamura M, Ohnuma H, Ishihara S, Kinoshita Y. Large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa. Clin J Gastroenterol 2018; 11:133-137. [PMID: 29305822 DOI: 10.1007/s12328-017-0816-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 12/27/2017] [Indexed: 12/30/2022]
Abstract
Gastritis cystica polyposa is a polypoid lesion that arises from the gastric mucosa at the gastrojejunal anastomotic site and is characterized by cystic dilation of the gastric glands. A 78-year-old man who underwent distal gastrectomy for a gastric ulcer with Billroth II reconstruction approximately 40 years previously, exhibited a gastritis cystica polyposa at the anastomotic site. Ulceration was observed on an annual endoscopic examination. Endoscopic ultrasonography revealed a submucosal hypoechoic mass with multiple cystic lesions. Gastrectomy was performed and histological examination revealed a large-cell neuroendocrine carcinoma with cystic dilation of the gastric glands. Here, we report the first case of a large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa. Endoscopic ultrasonography was effective at diagnosing a submucosal hypoechoic mass with cystic dilation of the gastric glands.
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Affiliation(s)
- Ryusaku Kusunoki
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan.
| | - Hirofumi Fujishiro
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Yuji Onoda
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Shinsuke Suemitsu
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Aya Fujiwara
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Kousuke Tsukano
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Satoshi Kotani
- Departments of Endoscopy, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Daisuke Kuroki
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Sayaka Ogawa
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Satoshi Yamanouchi
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Masahito Aimi
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Satoko Ito
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Youichi Miyaoka
- Departments of Endoscopy, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Tatsuya Miyake
- Departments of Hepatology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Naruaki Kohge
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Tomonori Imaoka
- Departments of Gastroenterology, Shimane Prefectural Central Hospital, 4-1-1 Himebara, Izumo, Shimane, 693-8555, Japan
| | - Michio Takamura
- Departments of Surgery, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Hideyuki Ohnuma
- Departments of Pathology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Shunji Ishihara
- Department of Internal Medicine 2, Shimane University School of Medicine, Izumo, Japan
| | - Yoshikazu Kinoshita
- Department of Internal Medicine 2, Shimane University School of Medicine, Izumo, Japan
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Chai SM, Brown IS, Kumarasinghe MP. Gastroenteropancreatic neuroendocrine neoplasms: selected pathology review and molecular updates. Histopathology 2017; 72:153-167. [DOI: 10.1111/his.13367] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Siaw M Chai
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
| | - Ian S Brown
- Envoi Pathology; Kelvin Grove; Queensland Australia
| | - M Priyanthi Kumarasinghe
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
- School of Pathology and Laboratory Medicine; University of Western Australia; Perth Australia
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Uesugi N, Sugimoto R, Eizuka M, Fujita Y, Osakabe M, Koeda K, Kosaka T, Yanai S, Ishida K, Sasaki A, Matsumoto T, Sugai T. Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. World J Clin Cases 2017; 5:397-402. [PMID: 29204428 PMCID: PMC5700389 DOI: 10.12998/wjcc.v5.i11.397] [Citation(s) in RCA: 2] [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: 05/31/2017] [Revised: 07/13/2017] [Accepted: 09/13/2017] [Indexed: 02/05/2023] Open
Abstract
Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor (NET) G2, NET G3, and neuroendocrine carcinoma (NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic imbalance (AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22q was commonly found in all components, AI of 4p was found in NET G3 and NEC components (but not in the NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within the same tumor.
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Affiliation(s)
- Noriyuki Uesugi
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Ryo Sugimoto
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Makoto Eizuka
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Yasuko Fujita
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Mitsumasa Osakabe
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Keisuke Koeda
- Department of Surgery, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Takashi Kosaka
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Shunichi Yanai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Kazuyuki Ishida
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Akira Sasaki
- Department of Surgery, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
| | - Tamotsu Sugai
- Department of Diagnostic Molecular Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
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Iida S, Ban S, Kato K, Endo S, Matsuo R, Hirano K, Okuyama T, Yamagata Y, Ueda Y. Gastric Adenocarcinoma with Dual Differentiation toward Neuroendocrine and α-Fetoprotein-Producing Features: Report of 2 Cases. Case Rep Gastroenterol 2017; 11:652-660. [PMID: 29282387 PMCID: PMC5731171 DOI: 10.1159/000480075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 08/01/2017] [Indexed: 11/19/2022] Open
Abstract
Some gastric carcinomas show composite features of neuroendocrine carcinoma (NEC) and α-fetoprotein (AFP)-producing carcinoma, which are very rare; only a few cases have been reported to date. We reviewed an additional 2 such cases of gastric carcinoma, which were both advanced aggressive tumors showing regional lymph node metastasis and distant metastasis. Both cases were accompanied by ordinary adenocarcinoma forms, implying that they had preceded the NEC and AFP-producing carcinoma components. A distinctive feature was the finding suggestive of dual differentiation of tumor cells to neuroendocrine and AFP-producing phenotypes, which was identified even in the metastatic tumor in the regional lymph node. Because both tumors predominantly showed poorly differentiated forms, the final pathologic diagnosis must rely on the immunohistochemistry. Pathologists should always keep in mind the existence of such tumors for the correct diagnosis of some gastric carcinomas with specific phenotypes, especially in pathologic diagnosis on biopsy.
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Affiliation(s)
- Shun Iida
- Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
| | - Shinichi Ban
- Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Japan
| | - Shinji Endo
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Japan
| | - Ryota Matsuo
- Division of Surgery, Shinmatsudo Central General Hospital, Matsudo, Japan
| | - Kosuke Hirano
- Department of Surgery, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
| | - Takashi Okuyama
- Department of Surgery, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
| | - Yukinori Yamagata
- Department of Surgery, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
| | - Yoshihiko Ueda
- Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan
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36
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Collision tumor of choriocarcinoma and small cell carcinoma of the stomach: A case report. Int J Surg Case Rep 2017; 37:216-220. [PMID: 28709051 PMCID: PMC5508625 DOI: 10.1016/j.ijscr.2017.06.055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 06/23/2017] [Accepted: 06/25/2017] [Indexed: 12/25/2022] Open
Abstract
We detailed a collision tumor of gastric choriocarcinoma and small cell carcinoma. We found a clear colliding point between choriocarcinoma and small cell carcinoma. Immunohistochemical staining results of HER2 were different for the two components. Introduction Both gastric choriocarcinoma and small cell carcinoma are extremely rare, both accounting for approximately 0.1% of all gastric cancers. Therefore, simultaneous occurrence of gastric choriocarcinoma and small cell carcinoma is even rarer. Presentation of case An 84-year-old Japanese man was referred to our hospital with the chief complaint of dysphagia. Laboratory data showed iron deficiency anemia. Contrast-enhanced computed tomography of the abdomen revealed thickened wall of the stomach at the fundus and several enlarged abdominal lymph nodes. Upper gastrointestinal endoscopy showed a friable gastric tumor with necrosis in the gastric cardia extending to the abdominal esophagus. Small cell carcinoma was diagnosed based on pathological examination of biopsy specimens. The anemia, which was probably because of tumor bleeding, progressed despite repeated transfusion; therefore, a semi-urgent laparotomy was performed to control hemorrhage. Finally, total gastrectomy and lymph node resection were performed. Based on pathological findings, a diagnosis of collision tumor of choriocarcinoma and small cell carcinoma of the stomach was confirmed. Discussion When encountering large tumors with necrosis or hemorrhage in the stomach, the possibility of choriocarcinoma component should be considered. Moreover, when small cell carcinoma is morphologically suspected, even if slightly, additional immunohistochemical staining must be performed. Conclusion This report detailed an extremely rare case of collision tumor of choriocarcinoma and small cell carcinoma of the stomach.
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Kim BS, Park YS, Yook JH, Kim BS. Comparison of relapse-free survival in gastric neuroendocrine carcinoma (WHO grade 3) and gastric carcinoma. Therap Adv Gastroenterol 2017; 10:407-415. [PMID: 28507599 PMCID: PMC5415098 DOI: 10.1177/1756283x17697870] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND We compared relapse-free survival (RFS) in gastric neuroendocrine carcinoma (WHO grade 3) and gastric carcinoma (GC). This is one of very few studies that compare the prognosis of poorly differentiated neuroendocrine carcinoma (WHO grade 3, G3 NEC) with that of GC. METHODS Between 1996 and 2014, 63 patients were diagnosed with G3 NEC of the stomach and 56 with gastric neuroendocrine tumors (NETs) with GC at Asan Medical Center in Seoul, Korea. We also randomly selected 762 patients diagnosed with GC between 1999 and 2008. RESULTS Patients with G3 NEC tumors that invaded the muscularis propria or shallower had poorer RFS than those with GC of the same type, while G3 NEC that invaded the subserosa or deeper had similar RFS to GC of that type. Patients diagnosed with G3 NEC with N0 or N2 had poorer RFS than the corresponding patients with GC, while those who had G3 NEC with N1 or N3 had similar RFS to the corresponding patients with GC. G3 NEC patients had poorer RFS than well-differentiated, moderately differentiated and poorly differentiated GC patients, while G3 NEC patients had similar RFS to that of those with signet ring cell carcinoma (SRC). In addition, patients with G3 NEC of stages I or IIa had poorer RFS than those with corresponding GC, while G3 NEC stage IIb or greater had similar RFS to the corresponding GC. CONCLUSIONS Non-advanced G3 NEC showed poorer RFS than GC excluding SRC, while advanced G3 NEC has a similar RFS to that of GC without SRC. Therefore, we recommend that patients with non-advanced G3 NEC of the stomach be given a more aggressive treatment and surveillance than those with non-advanced GC excluding SRC.
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Affiliation(s)
- Beom Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jeong Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
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38
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Girardi DM, Silva ACB, Rêgo JFM, Coudry RA, Riechelmann RP. Unraveling molecular pathways of poorly differentiated neuroendocrine carcinomas of the gastroenteropancreatic system: A systematic review. Cancer Treat Rev 2017; 56:28-35. [PMID: 28456055 DOI: 10.1016/j.ctrv.2017.04.002] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 04/04/2017] [Accepted: 04/05/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive tumors. Their molecular pathogenesis is still largely unknown, and consequently, the best therapeutic management also remains to be determined. We conducted a systematic review on molecular alterations found in gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of targeted therapies in setting. MATERIALS AND METHODS Systematic review of studies about molecular features in tumor tissues of patients with GEP-NECs. The Medline, Lilacs, Embase, Cochrane, Scopus and Opengrey databases were sought, without time, study design or language restrictions. RESULTS Of the 1.564 studies retrieved, 41 were eligible: 33 were retrospective studies and eight were case reports. The studies spanned the years 1997-2017 and involved mostly colorectal, stomach and pancreas primary tumors. Molecular alterations in the TP53 gene and the p53 protein expression were the most commonly observed, regardless of the primary site. Other consistently found molecular alterations were microsatellite instability (MSI) in approximately 10% of gastric and colorectal NEC, and altered signaling cascades of p16/Rb/cyclin D1, Hedgehog and Notch pathways, and somatic mutations in KRAS, BRAF, RB1 and Bcl2. In studies of mixed adeno-neuroendocrine carcinomas (MANECs) the molecular features of GEP-NEC largely resemble their carcinoma/adenocarcinomas tumor counterparts. CONCLUSIONS Despite the paucity of data about the molecular drivers associated with GEP-NEC, some alterations may be potentially targeted with new cancer-directed therapies. Collaborative clinical trials for patients with advanced GEP-NEC are urgently needed.
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Affiliation(s)
- Daniel M Girardi
- Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil.
| | - Andrea C B Silva
- Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil.
| | - Juliana Florinda M Rêgo
- Unit of Oncology and Hematology, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Rio Grande do Norte, Brazil.
| | | | - Rachel P Riechelmann
- Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil; Oncology Center, Hospital Sírio Libanês, São Paulo, Brazil.
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39
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Makuuchi R, Terashima M, Kusuhara M, Nakajima T, Serizawa M, Hatakeyama K, Ohshima K, Urakami K, Yamaguchi K. Comprehensive analysis of gene mutation and expression profiles in neuroendocrine carcinomas of the stomach. Biomed Res 2017; 38:19-27. [PMID: 28239029 DOI: 10.2220/biomedres.38.19] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The gene mutation and expression profiles of gastric neuroendocrine carcinoma (NEC) have not been comprehensively determined. Here, we examined the gene mutation and expression profiles of NEC using whole exome sequencing (WES) and microarray analysis. Six patients with gastric NEC and 13 with gastric adenocarcinoma (GAD) were included in this study. Single nucleotide variants were compared and multivariate statistical investigation with orthogonal partial least squares discriminant analysis (OPLS-DA) was performed to compare the difference in expression profiles between NEC and GAD. NEC showed a significantly higher mutation rate than GAD and the percentage difference in the mutation pattern of NEC compared with GAD was 92.8%. OPLSDA clearly discriminated between NEC and GAD. We identified 35 genes, including CPLX2 (Complexin 2), which were expressed more strongly in NEC than in GAD, of which 14 were neural-related. Immunohistochemical analysis showed the strong expression of CPLX2 in all NECs, versus expression in only 2 of 13 GADs. Gastric NEC had a specific mutation pattern with a significantly higher gene mutation rate than GAD, and completely differed from GAD on the basis of gene expression profile. CPLX2 might be a potential novel biomarker for the diagnosis of NEC.
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Affiliation(s)
- Rie Makuuchi
- Division of Gastric Surgery, Shizuoka Cancer Center
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40
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Nie L, Li M, He X, Feng A, Wu H, Fan X. Gastric mixed adenoneuroendocrine carcinoma: correlation of histologic characteristics with prognosis. Ann Diagn Pathol 2016; 25:48-53. [PMID: 27806846 DOI: 10.1016/j.anndiagpath.2016.09.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 09/11/2016] [Accepted: 09/13/2016] [Indexed: 12/14/2022]
Abstract
Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.
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Affiliation(s)
- Ling Nie
- Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Mingna Li
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xiaofeng He
- Department of Cardiothoracic Surgery, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Anning Feng
- Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Hongyan Wu
- Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiangshan Fan
- Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
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41
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Aoyagi K, Kizaki J, Isobe T, Akagi Y. A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:274-9. [PMID: 27102318 PMCID: PMC4844275 DOI: 10.12659/ajcr.896625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Patient: Male, 67 Final Diagnosis: Gastric cancer with neuroendocrine carcinoma Symptoms: — Medication: — Clinical Procedure: Total gastrectomy • splenectomy with D2 lymph node dissection Specialty: Surgery
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Affiliation(s)
- Keishiro Aoyagi
- Department of Surgery, Kurume University, School of Medicine, Kurume, Fukuoka, Japan
| | - Junya Kizaki
- Department of Surgery, Kurume University, School of Medicine, Kurume, Fukuoka, Japan
| | - Taro Isobe
- Department of Surgery, Kurume University, School of Medicine, Kurume, Fukuoka, Japan
| | - Yoshito Akagi
- Department of Surgery, Kurume University, School of Medicine, Kurume, Fukuoka, Japan
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Wei JM, Zhang ZZ, Shen YY, Shen DP, Ni XZ. A rare gastric neuroendocrine carcinoma coexisting with Brunner's gland adenoma: A case report. Oncol Lett 2015; 10:1251-1254. [PMID: 26622658 DOI: 10.3892/ol.2015.3465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 01/22/2015] [Indexed: 11/06/2022] Open
Abstract
Gastric neuroendocrine carcinoma (G-NEC) is a rare neoplasm known for its aggressive behavior and poor prognosis. Brunner's gland adenoma (BGA) is a rare benign proliferative lesion that develops most commonly in the duodenum. To the best of our knowledge, no cases of G-NEC coexisting with BGA have previously been reported. The present study therefore reports the first case of G-NEC combined with BGA. A 67-year-old female presented with upper abdominal discomfort. No distant metastases were detected upon pre-operative abdominal computed tomography imaging. The patient underwent a radical distal gastrectomy, D2 lymphadenectomy and Billroth I gastroenterostomy. The resected masses were histologically confirmed to be G-NEC and BGA, respectively. The patient did not receive neoadjuvant or adjuvant chemotherapy or radiotherapy, and remains alive with no evidence of metastasis or recurrence at four years post-surgery.
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Affiliation(s)
- Jian-Ming Wei
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Zi-Zhen Zhang
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Yan-Ying Shen
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Dan-Ping Shen
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Xing-Zhi Ni
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
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Kishi K, Fujisawa A, Horikita M, Nakai Y, Ooshimo K, Kishi F, Kimura M, Lin CC, Takayama T. Unusual endoscopic findings of gastric neuroendocrine tumor. THE JOURNAL OF MEDICAL INVESTIGATION 2015; 62:251-7. [PMID: 26399359 DOI: 10.2152/jmi.62.251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Gastric neuroendocrine tumor (NET) is sometimes found as a submucosal tumor on upper gastrointestinal endoscopy. Gastric NET with malignant profile and neuroendocrine carcinoma (NEC) show various forms which are difficult to distinguish from gastric cancer and other disease. We report a case of a cauliflower-shaped NET of the stomach. A 61-year-old man was referred to our hospital with a complaint of abdominal fullness. Upper gastrointestinal endoscopic examination revealed an unusual, whitish cauliflower-shaped tumor that belongs to Borrmann type I on the lesser curvature of the gastric antrum. Histological examination of the biopsy specimen revealed NET G2, because the tumor cells were CD56- and synaptophysin-positive by immunohistochemical analysis. A distal gastrectomy with D2 lymphadenectomy was performed. A recurrence in the liver was revealed by follow up computed tomography after 11 months from operation. Combined chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP) was treated. The patient achieved a partial response, but he died after 31 months from gastrectomy. There is no independent, large-scaled prospective study and no standard treatment for gastric NETs with distant metastases. Our case is reported with a literature review of the treatment of metastatic gastric NET G2.
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Affiliation(s)
- Kazuhiro Kishi
- Department of Gastroenterology, Kagawa Prefectural Shirotori Hospital
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44
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Solid-pseudopapillary neoplasm of the pancreas with extensive pleomorphic neuroendocrine differentiation. Pathology 2015; 47:468-72. [DOI: 10.1097/pat.0000000000000279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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45
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Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review. Diagnostics (Basel) 2015; 5:119-76. [PMID: 26854147 PMCID: PMC4665594 DOI: 10.3390/diagnostics5020119] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 03/24/2015] [Accepted: 03/26/2015] [Indexed: 02/07/2023] Open
Abstract
To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities.
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46
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A resected case of neuroendocrine carcinoma of the stomach with unusual lymph node metastasis. Med Mol Morphol 2015; 49:34-41. [DOI: 10.1007/s00795-015-0100-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 03/18/2015] [Indexed: 01/14/2023]
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47
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Gastric mixed adenoneuroendocrine carcinoma with thyroid transcription factor-1-positive neuroendocrine component. Clin J Gastroenterol 2015; 8:82-7. [DOI: 10.1007/s12328-015-0562-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 03/04/2015] [Indexed: 01/04/2023]
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48
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Park JY, Ryu MH, Park YS, Park HJ, Ryoo BY, Kim MG, Yook JH, Kim BS, Kang YK. Prognostic significance of neuroendocrine components in gastric carcinomas. Eur J Cancer 2014; 50:2802-9. [PMID: 25201164 DOI: 10.1016/j.ejca.2014.08.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 07/06/2014] [Accepted: 08/05/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gastric neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs) are aggressive tumours but the prognostic significance of a neuroendocrine component in <30% of the tumour remains unclear. Here, the implication of neuroendocrine components in gastric carcinomas was assessed according to proportion. METHODS Surgically resected primary gastric carcinomas with neuroendocrine morphology (NEM; n=88) from 2000 to 2012 at Asan Medical Center were retrospectively reviewed. Neuroendocrine differentiation (NED) was defined as immunopositivity for one of three neuroendocrine markers (synaptophysin, chromogranin or CD56) within the NEM area. To validate the prognostic significance of NED, these cases were compared with 650 randomly selected gastric adenocarcinomas without NEM from the same time period. RESULTS Gastric carcinomas with NEM were reclassified as NEC (⩾70% NED, n=47), MANEC (30-70% NED, n=10), gastric carcinoma with 10-30% NED (GCNED, n=8) and carcinoma with <10% NED (n=23). The survival rates of patients with ⩾10% NED were significantly poorer than those with <10% NED but no survival difference was observed between NEC and MANEC. In univariate analyses, older age (⩾60years), larger tumour size (⩾4cm), advanced stage group, ⩾10% NED and lymphovascular or perineural invasion were indicative of a poor prognosis. Stage group and ⩾10% NED remained as independent prognostic factors by multivariate analysis. CONCLUSIONS A minor proportion (10-30%) of NED should not be overlooked in gastric carcinomas with NEM. NED should be carefully evaluated to predict patient outcomes and plan optimal additional therapies.
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Affiliation(s)
- Ji Y Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea.
| | - Hye Jin Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Min Gyu Kim
- Department of Surgery, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri, Gyeonggi-do 471-701, Republic of Korea
| | - Jeong Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Byung Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea
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Domori K, Nishikura K, Ajioka Y, Aoyagi Y. Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis. Gastric Cancer 2014; 17:263-72. [PMID: 23828549 DOI: 10.1007/s10120-013-0281-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 06/11/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric neuroendocrine neoplasia has been classified as neuroendocrine tumor (NET), a less-malignant type, and neuroendocrine carcinoma (NEC), a more-malignant type. We investigated phenotypic expression profiles to clarify the differences between NET and NEC in terms of histopathology and carcinogenesis. METHODS We assayed 86 cases of gastric neuroendocrine neoplasms (NET G1, n = 25; NET G2, n = 9; NEC, n = 52), using six exocrine markers (MUC5AC, human gastric mucin, MUC6, M-GGMC-1, MUC2, and CDX2). RESULTS NEC frequently coexisted with adenocarcinomatous components (75 %; 39 of 52) and the majority (71.8 %; 28 of 39) showed intraglandular endocrine cell hyperplasia, although no cases of NET showed adenocarcinomatous components. Mucin phenotype significantly differed between NET and NEC; none of NET cases expressed any exocrine markers other than CDX2, although the majority of NEC (86.5 %; 45 of 52) expressed at least one or more exocrine markers with various positive rates for each marker (range, 8.2-74.0 %). Each NEC component showed only the phenotype expressed in the adenocarcinomatous component in the same tumor. Furthermore, double immunohistochemistry revealed dual expression of CDX2 and chromogranin A in half the NEC cases (23 of 46). CONCLUSIONS These data suggest that gastric NETs (G1 and G2) and NECs have different processes of carcinogenesis, and gastric NECs may be generated from preceding adenocarcinomas.
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Affiliation(s)
- Koji Domori
- Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
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Kadowaki Y, Nishimura T, Komoto S, Yuasa T, Tamura R, Okamoto T, Ishido N. Gastroduodenal intussusception caused by a gastric collision tumor consisting of adenocarcinoma and neuroendocrine carcinoma. Case Rep Gastroenterol 2014; 8:89-94. [PMID: 24803892 PMCID: PMC3999580 DOI: 10.1159/000356818] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Adenocarcinoma is the most common histological type of gastric tumor. Gastric tumor arising from collision of an adenocarcinoma with a neuroendocrine carcinoma is extremely rare. Moreover, this uncommon gastric collision tumor in our case had prolapsed into the duodenum. A 77-year-old woman was admitted to our hospital complaining of vomiting and severe weight loss. Abdominal X-ray showed gastric distension, and computed tomography revealed a duodenal giant mass spreading from the bulb to the horizontal part of the duodenum. Upper gastrointestinal endoscopy was not helpful in confirming the diagnosis of the tumor. We suspected duodenal malignant tumor and performed laparotomy. The operative findings indicated that the gastric antrum was deeply invaginated into the duodenum because of the gastric tumor. Partial resection of the stomach and duodenum was performed because the tumor was irreducible. Intraoperative diagnosis of the frozen section was well-differentiated adenocarcinoma and undifferentiated carcinoma. Additional distal gastrectomy with lymphadenectomy was performed. We herein report the first case of gastroduodenal intussusception caused by a gastric collision tumor consisting of well-differentiated adenocarcinoma and poorly differentiated neuroendocrine carcinoma.
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Affiliation(s)
| | | | - Satoshi Komoto
- Department of Surgery, Kobe Red Cross Hospital, Kobe, Japan
| | - Takeshi Yuasa
- Department of Surgery, Kobe Red Cross Hospital, Kobe, Japan
| | - Ryuji Tamura
- Department of Surgery, Kobe Red Cross Hospital, Kobe, Japan
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