Histopathology of gastrointestinal neuroendocrine neoplasms (original) (raw)
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Neuroendocrine neoplasms (NENs) of the digestive system are composed of cells with a neuroendocrine phenotype. These tumors produce and secrete peptide hormones and biogenic amines and they are called neuroendocrine neoplasms because of the marker proteins that they share with the neural cell system. The classification and nomenclature used to designate NENs have undergone changes over the past decades due to the accumulation of evidence related to the biological characteristics and their evolution. The European Neuroendocrine Tumor Society (ENETS) proposed a classification system based on the tumor grading and staging according to their localization. The latest internationally recognized NEN classification was published by the World Health Organization (WHO) in 2010. In accordance with the 2010 WHO criteria, the determination of the NEN malignancy potential is based on grading, depending on the mitotic activity and the Ki67 proliferation index, as well as on the tumor TNM stage. It is worth emphasizing that the terms neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC), without reference to grading or differentiation, are inadequate for prognostic assessment or the therapy determination, being inappropriate in pathology reports. The functional status of the tumor is based on the clinical findings but not on the pathological data or immunohistochemically profile. Despite the inability to establish a single system of sites, these are common features to establish the basis of most systems, documentation of these features allowing for greater reliability in the pathology reporting of these neoplasms.
Ann Ital Chir, Digital Edition 2020; , 2020
Recent classifications systems for gastroenteropancreatic neuroendocrine tumors. A single-center experience AIM: In this study, we aimed to review the demographic histopathological and clinical findings and long-term results of our GEP-NET cases, as well as to re-evaluate our cases according to the new classification systems. MATERIAL AND METHOD: 46 patients diagnosed as GEPNETs were presented. Immunohistochemical studies were performed in all cases. The cases were divided into 3 groups according to their embryogenic origin (Foregut, Midgut and Hindgut). All cases re-evaluated according to recent WHO (2019) and AJCC (2017) TNM calcification. Investigation was made to find differences between the embryonic origins and to find correlation between stage and grading systems with each other. RESULTS: The most common localization was appendix (52.3%) The distribution of cases according to embryologic origin were as follows: foregut tumors 13 cases (27.7%), midgut tumors 27 cases (57.4%) and hindgut tumors in 6 cases (12.8%). The Ki-67 ratio was evaluated in all patients, with a mean of 6.34%±2.51 (range: 1-80). The Ki-67 ratio was less than 3% in 82.6% of patients. Mitotic count was less than 2 per/10 HPF in 76% of patients. According to WHO 2019 most of patients were Grade 1 Neuroendocrine Tumor (65.2%) and there were only 2 Neuroendocrine Carcinoma (NEC) cases. According to AJCC 2017 most cases were Stage 1 (52.1%) and only 4 cases were Stage 4. The grades and stages of our cases were statistically significantly correlated. Overall survival did not differ significantly with regard to embryologic origin (log-rank test, p=0.062). The median overall survival was 106±7.4 months. The 5-year cumulative survival rate was 84.1±5.6 years. Seven patients died during this time with a median time of 5 months (range: 1-31 months). In the Cox regression analysis, the percentage of Ki-67 was found to have a statistically significant effect on overall survival (p=0.000) CONCLUSION: Correlation was noticed between WHO 2019 and AJCC 2017 classification for grade and stage and controlled trials must be undertaken to develop a single diagnostic algorithm and to change the future management of such patients.
Journal of gastrointestinal oncology, 2017
The gastroenteropancreatic neuroendocrine tumors (GEPNET) have a characteristic histologic appearance unrelated of the exact site of origin. However the behavior of these tumors are different in each of these sites. In this article we study the clinicopathological features of GEPNET. These tumors were classified and graded according to WHO 2010 criteria. The immunohistochemical (IHC) features were evaluated and the grade of the tumor was correlated with Ki67. A total of 40 cases of GEPNET diagnosed on biopsies as well as resected specimens were analyzed from January 2012 to June 2015. There were 28 resected specimens and 12 biopsies. Majority of the gastric neuroendocrine tumors (NET) showed classic morphology of cells arranged in islands. There were 3 cases each of grade 1 and grade 2 and one was diagnosed as mixed adenoneuroendocrine carcinoma (MANEC). All the duodenal NET were well differentiated (grade 1). There were 8 cases in colon and rectum, of which 4 cases were grade 3 and...
Journal of the Chinese Medical Association : JCMA, 2015
High-grade malignant mixed adenoneuroendocrine carcinoma (MANEC) is a highly malignant combined neoplasm formed by an adenocarcinomatous component and a poorly differentiated (Grade 3) neuroendocrine (NE) carcinoma. Tumors from 21 patients with gastrointestinal high-grade malignant MANECs or tumors with varying percentages of Grade 3 NE component were examined, and the NE component was confirmed by morphological analysis and immunohistochemical staining. Patients were divided into high NE (NE component > 50% in the primary tumor) and low NE (NE component ≤ 50% in the primary tumor) component groups. High NE component was a poor prognostic factor for patients with high grade MANEC (p = 0.021). Out of 13 patients with high-grade malignant MANEC, eight had a pure NE component, one had a pure adenocarcinomatous component, and four had mixed-type cancer in the metastatic lymph nodes. We further enrolled eight patients who had a Grade 3 NE component in the primary tumor and found that ...
Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms
Cancers, 2022
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape ...
Clinicopathological profile of neuroendocrine tumors of gastrointestinal tract
IP Journal of Diagnostic Pathology and Oncology, 2020
Introduction: Neuroendocrine neoplasms are derived predominately from enterochromaffin or Kulchitsky's cells. The estimated prevalence of neuroendocrine tumors (NET) is 1 to 2 cases per 100,000 people, of which gastrointestinal tract (GIT) is the most common site. And being a rare tumor, it is less studied Aim of the Study: To study the clinicopathological profile of Neuroendocrine tumors of GIT. Materials and Methods: All specimens of neuroendocrine tumors received from the Department of Surgery and Department of digestive health diseases during the period from September 2008 to September 2012 were included. Clinical details were collected from the medical records in all cases. The tumors were classified based on WHO classification 2010 using morphological findings on H&E slides. Immunohistochemistry was done in 40 cases using Synaptophysin, Chromogranin and Neuron specific enolase. Results: There were 886 neoplasms diagnosed in GIT of which 53 (5.98%) were NET. The mean age of presentation was 50 years. The male: Female ratio observed is 2:1. The most common presenting symptoms were abdominal pain followed by loss of appetite and weight. Carcinoid syndrome was seen in 2/53 (3.8%) patients .The most common site involved was Stomach followed by duodenum and ileum. NET Grade 1 was seen in 22 cases, NET Grade 2 was seen in 9cases, NET Grade3 was seen 4 cases and mixed adenocarcinoma and neuroendocrine carcinoma (MANEC) was seen in 18 cases. Metastasis to liver was seen in 3 cases Most of the NET tumors expressed the IHC markers, 95% were positive for NSE, 87.5% were positive for Synaptophysin and 82.5% cases were positive for Chromogranin Conclusion: Neuroendocrine tumors (NETs) are uncommon malignancies of GIT. Stomach was the most common anatomical site. NET grade 1 was the most common histological subtype. IHC markers NSE, Synaptophysin and chromogranin can be used in diagnosis of NETs
Cureus, 2021
The two broad subcategories of neuroendocrine neoplasms (NENs) are well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs), based on tumor architecture and cytology. Grade 3 WDNETs are a subset of WDNETs that not only are high grade by mitotic activity or proliferative index but exhibit a well-differentiated histology. In this study, we evaluated the clinicopathological features of primary neuroendocrine tumors of the gastrointestinal (GI)/pancreatobiliary tract with emphasis on high-grade WDNETs, as it is a newly defined entity. Methods We conducted a retrospective observational study, including a total number of 122 cases of primary GI and pancreatobiliary tract NENs. Slides and blocks of all cases were retrieved from the departmental archives. Immunohistochemical stains including Ki67 were applied to selected tissue blocks of all cases. Tumors were then evaluated for their histological differentiation and tumor grade. Results Our results showed that the mean age of patients was 46.8 ± 17.1 years. Majority of the NENs were GI tract origin (86.9%). The most common site of tumor in gastroenteropancreatic tract was the small bowel (31.1%), followed by the stomach (26.2%). Ninety five percent of the tumors were WDNETs, of which the most common grade was G2. The mean Ki67 index was 15.8 ± 23.8. Grade 3 WDNETs were noted to have an older mean age than grades 1 and 2 WDNETs. Ten out of 102 (9.8%) WDNETs of GI tract were grade 3, compared with four out of 14 (28.6%) of pancreatobiliary tract. Conclusion In this study, we found that high-grade (grade 3) WDNETs were more frequent in pancreatobiliary tract than GI tract. Moreover, high-grade WDNETs were associated with a higher mean age than low-grade (grade 1-2) WDNETs. It is extremely important to recognize this subset (high grade) of WDNETs and to distinguish it from PDNECs, as the latter are known to be associated with a worse overall survival. Despite high mitotic rate/proliferative index, high-grade WDNETs are characterized by organoid architecture and monomorphic cell population.
Mixed Adenoneuroendocrine Carcinomas (MANECs) of the Gastrointestinal Tract: An Update
Cancers, 2012
The systematic application of immunohistochemical techniques to the study of tumors has led to the recognition that neuroendocrine cells occur rather frequently in exocrine neoplasms of the gut. It is now well known that there is a wide spectrum of combinations of exocrine and neuroendocrine components, ranging from adenomas or carcinomas with interspersed neuroendocrine cells at one extreme to classical neuroendocrine tumors with a focal exocrine component at the other. In addition, both exocrine and neuroendocrine components can have different morphological features ranging, for the former, from adenomas to adenocarcinomas with different degrees of differentiation and, for the latter, from well differentiated to poorly differentiated neuroendocrine tumors. However, although this range of combinations of neuroendocrine and exocrine components is frequently observed in routine practice, mixed exocrine-neuroendocrine carcinomas, now renamed as mixed adenoneuroendocrine carcinomas (MANECs), are rare; these are, by definition, neoplasms in which each component represents at least 30% of the lesion. Gastrointestinal MANECs can be stratified in different prognostic categories according to the grade of malignancy of each component. The present paper is an overview of the main clinicopathological, morphological, immunohistochemical and molecular features of this specific rare tumor type.