Gallbladder neuroendocrine neoplasms: clinical characteristics, management, and survival in nine cases

Aims: Gastrointestinal and pancreatobiliary neuroendocrine tumors (GNETs) are rare malignancies, with gallbladder neuroendocrine neoplasms (GB-NENs) representing less than 0.5% of all NETs. This study aims to describe the clinical features, management strategies, and outcomes of gallbladder neuroendocrine neoplasms treated within the West Algerian NET Network.

Materials and Methods. A retrospective analysis was conducted on 9 cases of gallbladder neuroendocrine neoplasms diagnosed between December 2015 and September 2024 from a total of 301 patients with Gastrointestinal and pancreatobiliary neuroendocrine tumors. Data were collected on age, sex, clinical findings, tumor grade, Ki-67 levels, stage, management, and survival outcomes.

Results. Among the 9 patients (6 females, 3 males; mean age: 58.56 years), 4 had well-differentiated NETs, and 5 had large cell neuroendocrine carcinomas. Common clinical presentations included right hypochondrial pain (100%), jaundice (22%), palpable mass (33%), and weight loss (56%). Surgical resection was performed in 3 cases, achieving R0 resection with negative margins. The overall survival was 8.7 months, with those undergoing curative surgery surviving a mean of 17.7 months compared to 4.2 months for non-surgical patients. Jaundice at diagnosis was significantly associated with poorer survival (mean survival: 2.5 months vs. 10.4 months without jaundice.

Conclusion. Gallbladder neuroendocrine neoplasms are rare tumors that present unique clinical challenges. This case series highlights the importance of early diagnosis and aggressive management, with jaundice at presentation serving as a critical prognostic factor. Surgical resection appears to offer potential survival benefits, though further studies are needed to refine management strategies for these rare neoplasms.

1. Ahmed M. Gastrointestinal neuroendocrine tumors in 2020. World J. Gastrointest. Oncol. 2020; 12 (8): 791. https://doi.org/10.4251/wjgo.v12.i8.791

2. Rindi G., Mete O., Uccella S., Basturk O., La Rosa S., Brosens L.A.A., Ezzat S., de Herder W.W., Klimstra D.S., Papotti M., Asa S.L. Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms. Endocr. Pathol. 2022; 33 (1): 115–154. https://doi.org/10.1007/s12022-022-09708-2

3. Tidjane A., Boudjenan N., Bengueddach A., Kadri A., Ikhlef N., Benmaarouf N., Tabeti B. Pure large cell neuroendocrine carcinoma of the gallbladder, is surgical relentlessness beneficial? A case report and literature review. Int. Cancer Conf. J. 2021; 10 (2): 127. https://doi.org/10.1007/s13691-020-00461-z

4. Cai X.C., Wu S.D. Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review. World J. Clin. Cases. 2022; 10 (23): 8212–8223. https://doi.org/10.12998/wjcc.v10.i23.8212

5. Miyamoto R., Kikuchi K., Uchida A., Ozawa M., Nagai K., Maeda M., Kemmochi A., Inagawa S., Yamamoto M. Large cell neuroendocrine carcinoma of the gallbladder: a case report and literature review. Int. Surg. 2016; 101 (9–10): 458–464. https://doi.org/10.9738/INTSURG-D-16-00122.1

6. Dasari B.V.M., Ionescu M.I., Pawlik T.M., Hodson J., Sutcliffe R.P., Roberts K.J., Muiesan P., Isaac J., Marudanayagam R., Mirza D.F. Outcomes of surgical resection of gallbladder cancer in patients presenting with jaundice: A systematic review and meta-analysis. J. Surg. Oncol. 2018; 118 (3): 477–485. https://doi.org/10.1002/jso.25186

7. Yang X.W., Yuan J.M., Chen J.Y., Yang J., Gao Q.G., Yan X.Z., Zhang B.H., Feng S., Wu M.C. The prognostic importance of jaundice in surgical resection with curative intent for gallbladder cancer. BMC Cancer. 2014; 14 (1): 652. https://doi.org/10.1186/1471-2407-14-652

8. IHPBA-APHPBA International Study Group of Gallbladder Cancer; Palepu J., Endo I., Chaudhari V.A., Murthy G.V.S., Chaudhuri S. et al. ‘IHPBA-APHPBA clinical practice guidelines’: international Delphi consensus recommendations for gallbladder cancer. HPB (Oxford). 2024; 26 (11): 1311–1326. https://doi.org/10.1016/j.hpb.2024.07.411

9. Tidjane A., Boudjenan-Serradj N., Khalifa S., Ikhlef N., Bengueddach A., Larbi H. et al. Adenosquamous carcinoma of gallbladder associated with biliopancreatic maljunction and Todani 1c choledochal cyst: A case report. Adv. Dig. Med. 2023; 10 (3): 184–188.

10. Gogna S., Samson D., Gachabayov M., Rojas A., Felsenreich D.M., Koo D., Gu K., Quintero L., Miller K.R., Azim A., Da Eric Dong X. Neuroendocrine neoplasms of the gallbladder: early detection and surgery is key to improved outcome. Langenbecks Arch. Surg. 2022; 407 (1): 197–206. https://doi.org/10.1007/s00423-021-02256-z

11. Arrivi G., Verrico M., Roberto M., Barchiesi G., Faggiano A., Marchetti P., Mazzuca F, Tomao S. Capecitabine and temozolomide (CAPTEM) in advanced neuroendocrine neoplasms (NENs): a systematic review and pooled analysis. Cancer Manag. Res. 2022; 14: 3507–3523. https://doi.org/10.2147/CMAR.S372776