Is There a Need for New Classifications to Predict Prognosis in Gastroenteropancreatic Neuroendocrine Carcinomas?

Objective: Neuroendocrine neoplasms (NEN) are frequently located in the lung and gastroenteropancreatic (GEP) system organs. Neuroendocrine carcinoma (NEC) constitutes 5% of GEP NENs and has a very high malignancy potential. In this study, it is aimed to determine a new threshold value in addition to the 20% Ki-67 proliferation index that was specified as a threshold value for predicting survival in patients with grade (G) 3 tumors according to World Health Organization (WHO) 2010 classification. Method: Demographic, clinicopathologic features and survival rates of 34 patients diagnosed with GEP NEC between 2008-2015 in İzmir Katip Celebi University Atatürk Training and Research Hospital Medical Pathology Clinic were evaluated retrospectively. Results: Most of the 34 (76.5%) cases were male and the average age was 63.9 years. Median survival rates were 15, and 7 months in patients with Ki-67 indexes of ≤65% and >65%, respectively (p=0.232). Conclusion: Recent studies have shown heterogeneity of high-grade NENs, identified as NEC and foreseen their subdivision into biological subgroups. The researchers suggest that the NECs should be divided into two categories as patients with Ki-67 indexes of 20-55% and >55%. In our study, the most significant difference in survival rates was observed when 65% was selected as threshold value for Ki-67 index which supports the results of other studies in the literature. Since the number of our cases is limited and it is a single-center study, the findings obtained needs to be further investigated in studies with greater number of case series.

Gastroenteropancreatic neuroendocrine tumors: clinicopathological evaluation at Shifa International Hospital, Islamabad. A single centre experience

Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have rarely been studied in the Pakistani population. We investigated the clinical characteristics of these tumors according to the updated World Health Organization (WHO) 2010 classification. Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018. Results: One hundred and eighteen patients (mean age, 52.2 years; male, 55.1%) were identified. 83.1% of the patients were symptomatic including5.1% functional tumors. Pancreas (28%) was the most frequent primary site noted. The most common histologic type was well differentiated neuroendocrine tumor (WDNET) in 81.4% followed by neuroendocrine carcinoma (NEC) in 16.1%. 45.8% cases of WDNET were grade 1, 27.1% were grade 2, and 8.5% were grade 3.15.3% had distant metastasis at the time of diagnosis with liver (77.7%) as the most common metastatic site. Synaptophysin positivity was seen in 96.8% of grade 1 & grade 2 WDNET, 100% of grade 3 WDNET and 92.3% of NEC and chromogranin was positive in 94.2% of grade 1 &grade 2 WDNET, 83.3% of grade 3 WDNET and 45.4% of NEC. Conclusion: GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most site of involvement by the GEP-NET however grade 3 WDNET had a predilection for the colon. Small cell carcinomas were commonly observed in esophagus. Keywords: Gastroenteropancreatic neuroendocrine tu­mor, well differentiated neuroendocrine tumor, neuroendocrine carcinoma. Continuous...

Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism

Background. The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods. From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results. Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p=0.017), were larger (p<0.001), and presented more vascular (p=0.004) and lymphatic (p=0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion. In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.

Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2 and neuroendocrine carcinoma: NEC) on the basis of Ki-67 proliferation index and mitotic count according to the 2010 WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic backround together with preclinical studies to develop new agents, including those already under investigation for SCLC, will be needed to improve the prognosis.

Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic

Objective.To characterize GEP-NENs in routine biopsies and surgical specimen in the Czech Republic and to evaluate how WHO Classification (2010) is acceptable in diagnostic practice.Methods.Paraffin-embedded blocks and bioptic reports were collected from 17 departments of pathology. Histologic slides were stained with H&E and immunohistologically for CgA, synaptophysin, and Ki-67.Results.Out of 28 gastric NENs, there were 22 NETs, G1, 5 NETs, G2, and 1 NEC. Ten duodenal NENs were NETs, G1. Among 27 NENs of jejunum and ileum, 23 were NETs, G1, 2 NETs, G2, and 1 NEC and 1 mixed adenoneuroendocrine carcinoma (MANEC). Among 42 appendiceal “incidentalomas”, 39 were NETs G1, 2 goblet cell carcinoids, and 1 MANEC. Out of 34 large intestinal NENs, 30 were NETs, G1, 3 NETs, G2, and 1 NEC. One small intestinal and 6 large bowel neoplasms were reclassified as poorly differentiated adenocarcinomas. In 12 pancreatic NENs, there were 7 NETs, G1, 3 NETs, G2, and 2 NECs.Conclusions.Our study demonstrates differences in GEP-NENs frequency in sites of origin in our region, comparing to other countries. Regarding routine bioptic diagnostics, we gave evidence that the WHO 2010 classification of NENs is fully acceptable for exact categorisation of tumours.