This paper briefly illustrates the basis, rules of application, and present outcome of the current World Health Organization (WHO) classification for neuroendocrine neoplasms. Established in 2010 upon the proposal from the European Neuroendocrine Tumor Society (ENETS), the WHO 2010 fostered some definitional changes (most notably the use of neuroendocrine tumor (NET) instead of carcinoid) and indicated the tools of grading and staging. Specific rules for its application were also defined. The data generated from the use of WHO 2010 classification substantially endorsed its rules and prognostic efficacy. In addition, the application demonstrated some issues, among which are the possible re-definition of the cutoff for grading G1 vs G2, as well as the possible identification of cases with somewhat different clinical behavior within the G3 neuroendocrine cancer class. Overall, since the recent introduction of WHO 2010 grading and staging, it appears wise to keep the current descriptors to avoid unnecessary confusion and to generate comparable data. Homogenous data on large series are ultimately needed to solve such issues.
The recent proposals for a TNM classification of midgut and hindgut endocrine tumors made by the European Neuroendocrine Tumor Society (ENETS) are presented and commented. Certain particular points, such as the evaluation of the risk of malignancy of an endocrine tumor discovered fortuitously after appendicectomy and the indication of an additional surgical treatment, are developed. Finally, other questions frequently asked about digestive endocrine tumors are addressed.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.
Tumors of the disseminated/diffuse neuroendocrine system (NET) are characterized by a common phenotype. However, the biology varies according to histomorphology, endocrine symptoms and organ of origin. The WHO classification takes these differences into account and uses a common framework, where the parameters size and extent of invasion vary according to the organ of origin. In order to achieve a further standardization of reporting the European Neuroendocrine Tumor Society (ENETS) recently proposed a tumor-node-metastasis (TNM) staging and grading system for gastro-entero-pancreatic NET.
Comparison of WHO Classifications (2004, 2010), the Hochwald grading system, and AJCC and ENETS staging systems in predicting prognosis in locoregional well-differentiated pancreatic neuroendocrine tumors.
It is difficult to predict prognosis in patients with locoregional well-differentiated (WD) pancreatic neuroendocrine tumors (PanNET). We aimed to examine commonly used stratification systems [World Health organization (WHO) 2004 and 2010 classifications, American Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society (ENETS) staging, and the Hochwald grading system] for their power in predicting recurrence-free survival (RFS) in these patients. Seventy-five such patients (mean age 56 y, mean follow-up 79 mo) who underwent resection with sufficient tissue material and follow-up data were studied. RFS was correlated with variable clinicopathologic features and stratified with above-mentioned systems. Concordance index (CI) was then calculated. With the WHO 2004 classification, 16, 35, and 24 PanNETs were classified as benign behavior, uncertain behavior, and WD endocrine carcinoma, respectively. By the WHO 2010 classification, 26, 41, and 8 tumors were grade 1, 2, and 3, respectively. Using the Hochwald system, 47 were low grade, and 28 were intermediate grade. The AJCC staging information was complete for 62 patients (13 had the lymph node status Nx) and included: stages IA (19/62), IB (10/62), IIA (10/62), and IIB (23/62). The ENETS staging information was stages I (16/62), IIa (8/62), IIb (14/62), IIIa (0/62), and IIIb (24/62). The average Ki-67 proliferation index (PI) was 8.1%. Factors that predicted RFS included tumor size, nodal metastasis, vascular invasion, perineural invasion, necrosis, mitosis, and Ki-67 PI (all P
Cites: J Clin Oncol. 2007 Dec 10;25(35):5609-1518065733
The lack of uniform criteria for coding of gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) has hampered previous epidemiological studies. The epidemiology of GEP-NEN was investigated in this study using currently available criteria.
All patients diagnosed with GEP-NEN between January 2003 and December 2013 in a well defined Norwegian population of approximately 350 000 people were included. Age- and sex-adjusted incidence rates were calculated. The current 2010 World Health Organization criteria, European Neuroendocrine Tumour Society classification and International Union Against Cancer (UICC) classification were used.
A total of 204 patients (114 male, 55.9 per cent) were identified. The median age at diagnosis was 61 (range 10-94) years. The annual overall crude incidence was 5.83 per 100,000 inhabitants, with an increasing trend (P = 0.033). The most frequent location was small intestine (60 patients, 29.4 per cent) followed by appendix (48 patients, 23.5 per cent) and pancreas (33 patients, 16.2 per cent). Grade 1 tumours were more common in gastrointestinal (100 patients, 58.5 per cent) than in pancreatic (9 patients, 27 per cent) NEN. According to the UICC classification, 77 patients (37.7 per cent) had stage I, 17 patients (8.3 per cent) stage II, 37 patients (18.1 per cent) stage III and 70 patients (34.3 per cent) had stage IV disease. No patient with stage I disease had grade 3 tumours; advanced tumour grade increased with stage.
A high crude incidence of GEP-NEN, at 5.83 per 100,000 inhabitants, was noted together with a significant increasing trend over time.
Gastroenteric neuroendocrine neoplasms (GE-NENs) display highly variable clinical behavior. In an attempt to assess a better prognostic description, in 2010, the World Health Organization (WHO) updated its previous classification, and the European Neuroendocrine Tumors Society (ENETS) proposed a new grading and TNM-based staging system. In the current study, the authors evaluated the prognostic significance of these models and compared their efficacy in describing patients' long-term survival to assess the best prognostic model currently available for clinicians.
The study cohort was composed of 145 patients with extrapancreatic GE-NEN who were observed from 1986 to 2008 at a single center and were classified according to the WHO and ENETS classifications. Survival evaluations were performed using Kaplan-Meyer analyses on 131 patients. Only deaths from neoplasia were considered. A P value
Neuroendocrine neoplasms (NEN) appear homogeneous in terms of morphology, but constitute a very heterogeneous group of tumors in terms of biological and clinical features. NEN may occur in any organ, but are most commonly observed in the lung and the gastroenteropancreatic system (GEP). The European Neuroendocrine Tumor Society (ENETS) developed guidelines in the last 5 years to standardize and improve the diagnosis and therapy of GEP-NEN. Taking these guidelines into account, the TNM classification of the Union for International Cancer Control (UICC) was introduced in 2009. The new GEP-NEN classification of the World Health Organization (WHO) was presented 1 year later. According to the guidelines of the ENETS, the UICC, and the WHO, the pathology classification of NEN of GEP consists of several basic components: (1) evidence of the neuroendocrine nature of the tumor, (2) histological distinction between well and poorly differentiated tumors, (3) proliferation-based grading. (4) TNM staging (including data about vascular invasion and resection margins), (5) with reference to the clinical question: evidence of hormones and biogenic amines, and (6) optional, especially in cases of initial diagnosis of NEN: expression of the somatostatin receptor type 2A. Based on these criteria, a standardized prognostic stratification of GEP-NEN can be performed in combination with other clinical parameters. The novel classifications constitute the basis for selecting the procedures of molecular and metabolic imaging as well as for tumor-specific treatments and permit comparisons of larger tumor populations. Close interdisciplinary cooperation is a prerequisite.
With increasing interest in neuroendocrine tumors (NETs), three staging systems for NETs of the colon and rectum have been published. Their prognostic relevance has not been examined and compared in an independent clinical database.
From the National Cancer Database (NCDB), 5457 patients diagnosed with colorectal neuroendocrine tumor (CRNETs) between 1998 and 2002 were staged according to the staging systems from (1) European Neuroendocrine Tumor Society (ENETS, 2006; n = 1537); (2) American Joint Committee on Cancer (AJCC, 2009; n = 1140); and (3) location-specific staging systems from the Surveillance Epidemiology and End Results (SEER, 2008; n = 942). Stage-stratified overall survival (OS) and Cox-specific concordance indices were calculated for each system. Independent prognostic factors were identified by multivariate analysis.
Five-year OS for stage I, II, III, and IV CRNETs as defined by the ENETS staging system were 90.8, 77.3, 53.1, and 14.8 %, respectively. For well-differentiated CRNETs, the 5-year OS for stage I, II, III, and IV as defined by the AJCC staging system were superior: 90.6, 83.9, 64.8, and 24.9 %, respectively. Both staging systems had a concordance index of 0.72. After specifying location in the colon versus rectum, all three systems demonstrated acceptable performance. Histologic grade was a significant independent predictor of OS not currently incorporated in the staging systems.
The three staging systems showed comparable prognostic stratification of CRNETs, while the AJCC and ENETS systems are the most parsimonious. The current analysis supports the use of the AJCC for well-differentiated disease and ENETS systems for all CRNETs until there is further evidence for modification.