Twenty years of gastroenteropancreatic neuroendocrine tumors: is reclassification worthwhile and feasible?

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.