Kentaro Kai a , * , Kaei Nasu b , Haruto Nishida c , Tsutomu Daa c , Ayumi Shikama d , Takaya Shiozaki e , Masamitsu Kurakazu f , Mitsutake Yano g , Yuko Imamura h , Hideki Tokunaga i , Kazuto Tasaki j , Yasushi Iida k , Yuki Yamada l , Hiroyuki Morisawa m , Satoshi Nakagawa n , Etsuko Fujimoto o , Tomohiko Tsuruta p , Harunobu Matsumoto a , Atsushi Arakawa q , Michiko Nonaka r , Hirokuni Takano k , Takashi Ushiwaka s , Taisuke Mori t , Kimihiko Ito u , Takashi Motohashi v , Norihiro Teramoto w , Takashi Yamada x
25 February 2020
Background: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. Methods: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). Results: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids ( n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher’s exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93–586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54–480; p < 0.01). Conclusion: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.