Clinical features of ovarian large-cell neuroendocrine carcinoma: Four case reports and review of the literature

Abstract

Abstract. The objective of the present study was to present 4 recently encountered ovarian large-cell neuroendocrine carcinoma (LCNEC) cases, and to evaluate their clinicopathological features in the context of the previously reported 29 LCNEC cases. First, we described the clinical features of 4 recently encountered cases. Routine H&E staining and immunohistochemistry for CD56, synaptophysin and chromogranin A were performed on sections of both the LCNEC and epithelial carcinoma components. Clinical data for the total of 33 LCNEC cases were summarized, and the Kaplan-Meier survival curve was estimated. Our cases were observed in women aged 42-81 years. One case is clinically classified as FIGO stage IV with multiple metastases, and the others are classified as FIGO stages Ic, IIc and IIIb by post-surgical findings. Pathological features, assessed by H&E staining, were similar to lung LCNEC, and at least one neuroendocrine marker was positive staining in both LCNEC and the epithelial component. One case was pure type LCNEC and the others were mixed carcinoma. Paclitaxel/carboplatin chemotherapy was performed for all cases and 3 of the 4 treatments were effective. The prognoses of our cases were as follows: 1 in stage Ic died from the disease after only 2 months, but the others survived, with or without recurrence, for 32-64 months, whereas the total 5-year survival of the 33 LCNEC cases was 34.9%. In summary, our 3 LCNEC cases revealed ordinary chemo-sensitivity, resulting in a better prognosis than those previously described, apart from 1 case which exhibited aggressive behavior. For the future, a retrospective survey to elucidate the prognostic factors and prospective clinical studies to evaluate the efficacy of treatment modalities of ovarian LCNEC are necessary, particularly for aggressive LCNEC cases. IntroductionThe World Health Organization (WHO) defines large-cell neuroendocrine carcinoma (LCNEC) as a tumor with a large nucleus and a tendency to have neuroendocrine differentiation, and it defines ovarian LCNECs as miscellaneous tumors (1). In Japan, the term LCNEC was described for the first time in The General Rules for Clinical and Pathological Management of Ovarian Tumors by the Japan Society of Obstetrics and Gynecology and the Japanese Society of Pathology in December 2009. Until these classifications were established, LCNEC had been classified as anaplastic or poorly differentiated carcinoma and was synonymous with undifferentiated carcinoma of the non-small cell neuroendocrine type (1,2). According to the WHO classification of lung cancer (3), the pathological structures by H&E staining reveal a characteristic organization, such as round nest and sheet-like formation with frequently central coagulative necrosis, and rosette-like formation of tumor cells is often observed everywhere. The nucleus is large with granular or coarse chromatin, a prominent nucleolus and moderate or abundant cytoplasm. Additionally, neuroendocrine differentiation by immunohistochemical analysis, such as chromogranin A, sy...

Role of diagnostic laparoscopy in patients with large cell neuroendocrine carcinoma of the ovary with cancerous peritonitis: case report and review of the literature

“…There were no significant differences between the cases with FIGO stage I/II (n = 28) and III/IV (n = 25), with total 5-year survival of 38.8 and 29.2% and median survival time of 19 and 9 months, respectively (p = 0.458). These results were almost similar to the previous report by Oshita et al [18], suggesting that cases with LCNEC showed much worse clinical outcomes than the other subtypes, such as epithelial ovarian cancer even in early disease, regardless of FIGO stage. In particular, cases with carcinomatous peritonitis (n = 11) showed significantly much poorer clinical outcomes than cases without carcinomatous peritonitis (n = 42), with median survival time of 7 and 20 months, respectively (p = 0.036), suggesting that a different therapeutic strategy should be considered in these cases ( Fig.…”

“…The clinicopathological features of 31 cases with FIGO stage I/II (Table 1) and 25 cases with FIGO stage III/IV (Table 2) [7,8,14,17,18,20,[25][26][27][28][29][30][31][32][33][34][35] were reviewed. A Kaplan-Meier survival curve (SPSS Statistics version 24; IBM, Armonk, NY) of all 53 cases excluding 3 cases without clinical outcome data showed total 5year survival of 34.6% and median survival time of 17 months.…”

“…Therefore, pathological examination has to be performed to differentiate non-epithelial ovarian cancer or other diseases including inflammation in these LCNEC cases. In the previous cases with stage III/IV [7,8,14,17,18,20,[25][26][27][28][29][30][31][32][33][34], most patients underwent laparotomy for diagnosis and treatment. However, complete surgery could not be performed in many cases, leading to the deterioration of the patients' general condition and much poorer outcomes.…”

Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review

“…This extremely rare clinical presentation of a huge mass arising from an anatomically normal ovary confirmed laparoscopically, 9 months back was reiterating the fact that this tumour was rapidly growing. Some authors have similar opinion [1][2][3][4][5][6].…”

Pure Large Cell Neuroendocrine Carcinoma of Ovary: A Rare Clinical Entity and Review of Literature

“…This extremely rare clinical presentation of a huge mass arising from an anatomically normal ovary confirmed laparoscopically, 9 months back was reiterating the fact that this tumour was rapidly growing. Some authors have similar opinion [1–6]. …”