title: Twenty years of gastroenteropancreatic neuroendocrine tumors: is reclassification worthwhile and feasible?
abstract: Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms with heterogeneous clinical behavior and potential long-term survival. In 2006/2007, the European Neuroendocrine Tumors Society introduced an important parameter, grade (based on mitoses and Ki-67 proliferation rate), which became part of the latest 2010-WHO classification. Since this is an important tool in the choice of therapeutic algorithm of patients with NETs, our aim was to audit whether retrospective reclassification is possible and feasible and correlate pathological findings with survival. From the histopathology archive, 338 GEP-NETs (1994-2014) were identified, of which 250 were diagnosed pre-2010 and 80 of these have needed, up till now, classification (morphology and grade-mitotic count/Ki-67). Morphology was well differentiated (WD) in 74 cases while only 6 cases were poorly differentiated (PD). Grade was reclassified: G1-45 cases (56 %); G2-28 cases (35 %); G3-7 cases (9 %). Overall survival (OS) in WD NETs was strikingly better compared to PD neoplasms. Differences in OS between grade were statistically significant (p < 0.0001) and, in particular, grade identified a subgroup of patients with WD lesions but with less favorable clinical behavior (OS at 5 years: G1-89 %; G2-48 %; G3-0 %; G1 vs G2 p = 0.03). Feasibility analysis quantified time for reclassification to be between 45 and 64 min/case. Our series confirms the importance of grade in prognostic stratification and underlines that reclassification is feasible, and may prove worthwhile in patient management, especially in view of the potential long survival of patients with NETs and risk of use of inappropriate therapies.
authors.affiliation: Histopathology, Department of Surgical Science (DISC), University of Genoa, Genoa, Italy.|IRCCS AOU San Martino IST, Largo R. Benzi, 10, 16132, Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Grillo
authors.affiliation: Endocrinology, Department of Internal Medicine (DIMI), University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy. manuela.albertelli@unige.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Albertelli
authors.affiliation: Endocrinology, Department of Internal Medicine (DIMI), University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Annunziata
authors.affiliation: IRCCS AOU San Martino IST, Largo R. Benzi, 10, 16132, Genoa, Italy.|Endocrinology, Department of Internal Medicine (DIMI), University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Boschetti
authors.affiliation: Endocrinology, Department of Internal Medicine (DIMI), University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.|Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, Via Palermo 636, 95122, Catania, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caff
authors.affiliation: Histopathology, Department of Surgical Science (DISC), University of Genoa, Genoa, Italy.|IRCCS AOU San Martino IST, Largo R. Benzi, 10, 16132, Genoa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pigozzi
authors.affiliation: IRCCS AOU San Martino IST, Largo R. Benzi, 10, 16132, Genoa, Italy.|Endocrinology, Department of Internal Medicine (DIMI), University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
authors.affiliation: Histopathology, Department of Surgical Science (DISC), University of Genoa, Genoa, Italy.|IRCCS AOU San Martino IST, Largo R. Benzi, 10, 16132, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Mastracci
mesh_terms: D006801:Humans; D007414:Intestinal Neoplasms / Q000145:classification* / Q000401:mortality / Q000473:pathology; D019394:Ki-67 Antigen; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000145:classification* / Q000401:mortality / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000145:classification* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000145:classification* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D019394:Ki-67 Antigen
keywords: Classification; Grade; Ki-67; Neuroendocrine tumors