Mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder: a case report

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Abstract

Background

Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare.

Case presentation

We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy.

Conclusions

GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

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Most cited references 14

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Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC).

A. Duffy, M Capanu, G K Abou-Alfa … (2008)

The incidence of gallbladder cancer (GBC) in the US is 1.2/100,000. This report examines the patterns of presentation, adjuvant treatment and survival of a large cohort of patients with GBC evaluated at MSKCC over a 10-year period. A retrospective analysis of patients referred to MSKCC with a diagnosis of GBC between January 1995 and December 2005 was performed. Patients were identified from the MSKCC cancer registry. Information extracted included, demographics, clinical and pathological stage, surgical management, pathology, adjuvant and palliative therapy, date of relapse, death or last follow-up. Date of diagnosis was defined as date of surgery or biopsy. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Four hundred thirty-five GBC cases were identified: 285 (65.5%) females,150 (34.5%) males. Median age 67 years (range 28-100). Pathology: 88% adenocarcinoma, 4% squamous, 3% neuroendocrine, 2% sarcoma. 36.6% presented as AJCC Stage IV. 47% were discovered incidentally at laparoscopic cholecystectomy. One hundred thirty-six of these were re-explored, of whom 100 (73.5%) had residual disease. Of those who underwent curative resections (N = 123), 8 (6.5%) received adjuvant chemotherapy, 8 (6.5%) chemoradiation alone and 8 (6.5%) both chemoradiation and systemic chemotherapy. Median overall survival for the cohort was 10.3 months (95% CI 8.8-11.8) with a median follow up of 26.6 months. The median survival for those presenting with stage Ia-III disease was 12.9 months (95% CI 11.7-15.8 months) and 5.8 months (95% CI 4.5-6.7) for those presenting with stage IV disease. Median survival was 15.7 months (95% CI 12.4-18.4) for those discovered incidentally at laparoscopic cholecystectomy. For those who underwent re-exploration, median survival was 14.6 months (95% CI 12.6-18.3) if residual disease was present, and 72 months (95% CI 34 to infinity) if no evidence of disease. The median survival for those who received adjuvant therapy was 23.4 months (95% CI 15.7-47). GBC is commonly diagnosed incidentally (47%). Re-exploration reveals a high incidence of residual disease (74%). Median survival is better for patients who have no evidence of disease on re-exploration (72 months) compared to those with residual disease detected (P < 0.0001). Overall prognosis is poor. Although we did not observe a survival benefit for those who received adjuvant therapy, the study did not have sufficient power to address this question. In addition, the number of patients who received adjuvant therapy was small with marked heterogeneity in clinical and therapeutic details, precluding any definitive conclusions being drawn. Prospective randomized trials of adjuvant therapy are needed in this disease. (c) 2008 Wiley-Liss, Inc.

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Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas.

Shunsuke Kondo, Yasushi Kojima, Shuichi Mitsunaga … (2010)

The combination chemotherapy consisting of cisplatin and etoposide, one of the standard regimens for small cell lung cancer, has been widely used to treat extrapulmonary poorly differentiated neuroendocrine carcinomas. However, there were no prior reports limited to the hepatobiliary tract and pancreas as the primary sites. We reviewed the cases in our database from October 1995 to January 2009 and retrospectively examined the clinical data of patients, with unresectable or recurrent poorly differentiated neuroendocrine carcinoma arising from the hepatobiliary tract and pancreas, who received combination chemotherapy with cisplatin and etoposide as the first-line treatment. The chemotherapy regimen consisted of cisplatin 80 mg/m(2) given intravenously on day 1 and etoposide 100 mg/m(2) intravenously on days 1-3, repeated every 3-4 weeks. Twenty-one patients were treated with the above regimen of cisplatin and etoposide combination chemotherapy. The primary tumor site was the liver in 2 patients, gallbladder in 8 patients, pancreas in 10 patients and ampulla of Vater in 1 patient. Although no complete responses were obtained, three patients had partial responses, resulting in an overall response rate of 14%. Median progression-free survival was 1.8 months, and median overall survival was 5.8 months. The major adverse events were myelosuppression and gastrointestinal toxicities, with Grade 3 or 4 neutropenia (90%), nausea (33%) and anorexia (24%). Cisplatin and etoposide combination as the first-line chemotherapy for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma had only marginal antitumor activity and relatively severe toxicity compared with previous studies on extrapulmonary poorly differentiated neuroendocrine carcinoma treated with the same regimen.

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Preneoplastic lesions in gallbladder cancer.

Xabier de Aretxabala, Juan Roa, Iván Roa … (2006)

Gallbladder cancer is an uncommon disease except in countries like Chile and areas of India and Japan. The knowledge regarding the etiology and mechanisms through which this neoplasia is developed is significantly less compared to other malignant tumors. The epithelial lesions involved in gallbladder carcinogenesis are dysplasia and adenomas that represent two biologically distinct carcinogenetic models. Dysplasia progresses to carcinoma in situ (CIS) and subsequently becomes invasive. Over 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia. Other authors have demonstrated adenomatous areas in carcinomas, or malignant transformation in an adenoma. The low incidence of gallbladder adenomas (0.14% of cholecystectomies) and the presence of adenomatous remnants in the neighboring mucosa to early carcinomas in less than 3% of the cases suggest the limited importance of this carcinogenic pathway. Epithelial dysplasia which is not associated with gallbladder cancer is observed in approximately 1% of cholecystectomies for symptomatic lithiasis. Metaplasia, dysplasia, and CIS are present in the mucosa adjacent to the cancer in 66%, 81.3%, and 69%, respectively. The average ages of patients with dysplasia not associated to cancer (51.9 years), early carcinomas (56.8 years), and advanced carcinomas (62.9 years) demonstrate a gradient which suggests the progression of these lesions. From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years. Copyright 2006 Wiley-Liss, Inc.

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Author and article information

Contributors

Tatsuki Ishikawa: taishika@east.ncc.go.jp

Journal

Journal ID (nlm-ta): Surg Case Rep

Journal ID (iso-abbrev): Surg Case Rep

Title: Surgical Case Reports

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Electronic): 2198-7793

Publication date (Electronic): 17 March 2021

Publication date PMC-release: 17 March 2021

Publication date Collection: December 2021

Volume: 7

Electronic Location Identifier: 70

Affiliations

[1 ]Department of Surgery, Omihachiman Community Medical Center, 1379 Tsuchidacho, Omihachimanshi, Shiga 523-0082 Japan

[2 ]Department of Pathology, Omihachiman Community Medical Center, 1379 Tsuchidacho, Omihachimanshi, Shiga 523-0082 Japan

Article

Publisher ID: 1152

DOI: 10.1186/s40792-021-01152-4

PMC ID: 7969674

PubMed ID: 33730263

SO-VID: b469ad93-34fc-46cc-83bb-a3f76a95fd99

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 December 2020

Date accepted : 7 March 2021

Custom metadata

Keywords: mixed neuroendocrine–non-neuroendocrine neoplasms,mixed adenoneuroendocrine carcinoma,gallbladder cancer

Data availability:

Keywords: mixed neuroendocrine–non-neuroendocrine neoplasms, mixed adenoneuroendocrine carcinoma, gallbladder cancer

Mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder: a case report

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Abstract

Background

Case presentation

Conclusions

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ScienceOpen Clinical Case Reports Collection

Most cited references 14

Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC).

Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas.

Preneoplastic lesions in gallbladder cancer.

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