Authors
S. RIBEIRO (1), F. DE MAEYER (2), M. DE MAN (1), S. CARTON (3), P. CUYLE (3), T. VANDAMME (4), C. VERSLYPE (5), I. BORBATH (6), P. DEMETTER (7), N. VAN DAMME (8), L. VAN EYCKEN (8), A. HOORENS (9), K. GEBOES (1) / [1] UZ Gent, Gent, Belgium, Gastroenterology, [2] AZ Sint-Elisabeth, Zottegem, Belgium, Gastroenterology, [3] Imelda Hospital, Bonheiden, Belgium, Gastroenterology, [4] Netwerk, UZA, Edegem, Belgium, Gastroenterology, [5] KU Leuven, , Belgium, Gastroenterology, [6] UCLouvain, , Belgium, Gastroenterology, [7] Institut Jules Bordet, , Belgium, Pathology, [8] Belgian Cancer Registry, Brussel, Belgium, Register, [9] UZ Gent, Gent, Belgium, Pathology
Introduction
Appendiceal neuroendocrine neoplasms (aNEN) are rare tumors. Classification systems have changed significantly and repeatedly over the years, largely because of changes in terminology. There is a definite need for unbiased data on the epidemiology of NEN. Most existing data are incomplete because they are retrieved from registries kept by groups of (expert) centers, such as the DNET registry. In Belgium, data on patient and tumor characteristics of all newly diagnosed cancers is collected in a national and population based registry, the Belgian Cancer Registry (BCR). The BCR also receives the pathology protocols describing results of (pre-)malignant specimens.
Aim
The aim of the present study is to have epidemiological data of aNEN in Belgium and to investigate the evolution of pathological reporting.
Methods
Pathology reports of all aNENs diagnosed between 2010 and 2015 were thoroughly reviewed. A significant part of pathologists in Belgium use the College of American Pathologists (CAP) guidelines, first introduced for NET in June 2012. All reports were checked for clinicopathological data including size of tumor, WHO grade (Ki 67), grade of differentiation, lymphovascular invasion, location, infiltration of the mesoappendix, nodal involvement and margin status, because treatment algorithms are based on these parameters. Right hemicolectomy should be offered to all patients with appendiceal neuroendocrine tumors (aNET) > 2cm. It is also suggested to advise right hemicolectomy in patients with grade (G)2 aNET. In patients with a tumor size between 1 and 2 cm, right hemicolectomy should be discussed based on certain risk factors. Classification was examined and adapted to the WHO 2019 classification, if necessary.
Results
We identified 584 aNENs over a period of 6 years, corresponding to a steady incidence of 0.9/100.000/year. It was impossible to verify classification in 185 cases because of missing pathological data. Fifty-one patients had to be reclassified according to the WHO 2019 guidelines. After reclassification, there were 348 NET G1, 50 NET G2 and 1 neuroendocrine carcinoma (NEC). Fifty-six% of patients were female, mean age 39y. The size of the tumor was mentioned in 94% of 584 cases. WHO grade and grade of differentiation were both retrievable in 44% of cases in 2010 and in 80% and 72% of cases respectively in 2015. Twenty-one NET G1 and 6 NET G2 tumors were larger than 2cm. We found no information on tumor size in 18 G1 and 3 G2 patients. 71 patients had a G1 tumor sized between 1 and 2 cm. At least 1 of the 4 commonly used prognostic factors was missing for all these patients; 2 prognostic factors were missing for 28 (39,4%) patients, and 3 or more were missing for 23 (32,3%) patients. 15 patients had a G2 tumor between 1 and 2 cm. Only 1 of these patients had all the risk factors reported while at least 1 of the 4 prognostic factors was missing for the majority of them (n= 14; 93,3%) and 2 or more prognostic factors were missing for 7 (46,7%) patients. Of note, depth of infiltration of the mesoappendix is not included in the CAP checklist.
Conclusions
Based on the Belgian cancer registry data, we can withhold an incidence for aNEN of 0.9/100.000/year. Tumor size was reported in the majority of cases. Most patients have NEN < 1cm. We have real life data on the evolution of reporting upon introduction of the new WHO grading system, with uptake in 80% of cases by 2015. 32% of cases could not be verified for correct classification because of missing pathological data. 9% of cases had to be reclassified, pointing out that previous reports based on retrospective datasets should be interpreted with caution and original pathological reports (or specimens) should be checked for specific parameters. Missing information in other parameters may be influenced by size, because these parameters only affect decisions in tumors between 1-2cm. However, in all but 1 of these cases at least 1 of the known risk factors were missing
