Biliary Neuroendocrine Neoplasms: Clinical Profiles, Management, and Analysis of Prognostic Factors

Abstract

Biliary neuroendocrine neoplasms (NENs) represent <1% of all NENs. The aim of this retrospective study is to present the clinical characteristics, management and prognosis profiles of 28 biliary NEN patients from a large tertiary center, and identify factors related to prognosis. Nine tumors originated from the gallbladder, two from the extrahepatic bile duct and 17 from the ampulla of Vater. One patient was classified as neuroendocrine tumor (NET) Grade 1, three patients were classified as NET Grade 2, 18 were graded neuroendocrine carcinoma (NEC) Grade 3 and six were classified as mixed adenoneuroendocrine carcinoma (MANEC). The overall survival rate and disease-free survival rate did not have statistically significant differences between tumors of different locations or different grading. Recurrence of disease correlated with poor prognosis (p < 0.001). Lymphovascular invasion and invasion beyond the submucosa were related to higher risk of local lymph node metastases. Multivariate analysis identified patient age (p = 0.021) and R0 resection margin (p = 0.027) as independent prognostic factors associated with overall survival. Our study included relatively large numbers of biliary tract NENs with intact follow-up information. Patients with biliary neuroendocrine tumors showed different clinical outcomes according to tumor locations and tumor grades. Achieving R0 resection is important for better prognosis.

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

“…Data on gender were provided in 77 studies (n = 983) [68][69][70][72][73][74][75]79,80,82,[84][85][86]88,[93][94][95][96][97][99][100][101]; 65.6% (n = 645) were male, and 34.4% (n = 338) were female. The frequency of the two genders according to the primary tumour site could be explored in 71 studies (n = 580) 68,70,[72][73][74]79,80,82,86,88,[93][94][95]97,100,101]. In the majority of subgroups per primary tumour site, the male gender was prevalent; stomach 89.5% (n = 68 out of 976), oesophagus/OGJ 86.1% (n = 87 out of 101), pancreas 66.7% (n = 24 out of 36), colon 63.2% (n = 43 out of 68), rectum 63.1% (n = 12 out of 19), small bowel 60.0% (n = 3 out of 5), anus 100% (n = 2 out of 2), and liver 100% (n = 1 out of 1), whereas among MiNENs from the biliary tract (male 47.8%; n = 11 out of 23) and the appendix (male 51.0%; n = 127 out of 249) the two genders were represented in roughly equal proportions.…”

“…The stage of the disease at diagnosis was noted in 77 studies (n = 2117) [68][69][70][73][74][75]79,80,[84][85][86][87][88]91,[94][95][96][98][99][100][101], and could be classified as follows; localised (Loc), curatively treated, with or without loco-regional nodal involvement, without distant metastases (81.6%; n = 1727); advanced (Adv), not suitable for curative treatment, and with or without distant metastases (18.4%; n = 390).…”

“…Among 69 studies (n = 667) reporting the grade of differentiation of the neuroendocrine component [11][12][13][14][15][16][17][18][19][21][22][23][24][25][26][27][28][29][54][55][56][57][58][59][60][61][62]68,71,[73][74][75]79,80,82,[84][85][86][87]89,[91][92][93]96,97,100,101], a large proportion of MiNENs (92.5%; n = 617) had a grade 3 neuroendocrine component, whereas 4.3% (n = 29) and 3.1% (n = 21) had a grade 1 and a grade 2 neuroendocrine component, respectively. Among MiNENs with a grade 3 neuroendocrine component, the morphological subtype (large cell or small cell) was reported in 25 studies (n = 241) [11,…”

What is New in the 2019 World Health Organization (WHO) Classification of Tumors of the Digestive System: Review of Selected Updates on Neuroendocrine Neoplasms, Appendiceal Tumors, and Molecular Testing

“…Biliary NENs are extremely rare, accounting for less than 1% of all NENs and are often incidentally detected during cholecystectomy. 34 NECs are even rarer accounting for 4% of all malignant gallbladder neoplasms according to some studies. 5,35 Both NETs and NECs have a slight female predominance and usually occur in the mid-seventh decade of life.…”

“…5,35 Both NETs and NECs have a slight female predominance and usually occur in the mid-seventh decade of life. 34 NETs of the biliary tract tend to be associated with intraepithelial papillary neoplasms. 36 The tumor cells are arranged in nests, trabeculae, and occasionally tubules.…”