Neuroendocrine Tumor Of Gallbladder Research Articles

Survival outcomes associated with treatment modalities in stage 4 gallbladder neuroendocrine tumors: A nationwide analysis.

e16295 Background: Gallbladder neuroendocrine tumors (GNETs) are rare, heterogeneous, and aggressive tumors of the gallbladder. GNETs usually present in the elderly ( > 60 years) and there are no clear clinical guidelines to treat stage 4 GNETs due to rarity. We evaluated therapeutic options for stage 4 GNETs. Methods: We included stage 4 GNETs diagnosed between 2004-2020 in the National Cancer Database. Treatment was stratified into combination therapy (Comb) - surgery (Sx) and chemotherapy (CT), Sx alone and CT alone. Survival outcomes were expressed as Kaplan-Meier curves and Cox proportional hazard model adjusting for age, Charlson-Deyo score (CDS) and sociodemographic variables like sex, race, ethnicity, insurance status, and facility location. We expressed survival outcomes as median overall survival (mOS, 95% CI) and time-dependent survival as hazard ratio (HR, 95% CI). Results: Of 242 patients with stage 4 GNETs, the median age was 64 years (range 29-90+ years), 62.4% were female, 66.9% had CDS of 0, 22.4% had CDS of 1, 10.8% had CDS ≥2, 98.7% had poorly differentiated tumor (grade 3 or 4), 70.3% were White, 85.9% were non-Hispanic, median size of the primary tumor was 10.7 cm (range 0.8-14.1 cm) and 47.8% were treated at academic or research program. 46 (19.0%) patients received Comb, 171 (70.7%) received CT and 25 (10.3%) patients received Sx alone. The mOS was 11.5 months (9.3-18.4), 9.4 months (7.9-11.2), 4.2 months (2.3-6.3) for Comb, CT and Sx, respectively (P < 0.001). Pairwise log-rank revealed no significant differences between Comb and CT groups (P = 0.07). In univariate Cox analysis, CDS ≥2 showed HR of 1.6 (1.0-2.4; p = 0.04), Sx showed HR of 1.7 (1.1-2.7; P = 0.02), and Medicare had HR of 1.35 (1.02-1.78; p = 0.037). However, on multivariate analysis, uninsured patients (HR = 5.16; 95% CI 1.50-17.7; P = 0.009) and those receiving Sx alone (HR = 2.09; 95% CI 1.27-3.46; P = 0.004) had unfavorable outcomes. Conclusions: The combination of primary site surgery with CT improves survival in stage 4 GNETs as compared to resection alone. However, there is no significant difference in survival in combination therapy and CT. We emphasize the need for robust prospective studies comparing the efficacy of chemotherapy, neoadjuvant and adjuvant chemotherapy for stage 4 GNETs.[Table: see text]

Unveiling inequalities: An analysis of treatment disparities of primary gallbladder neuroendocrine tumors by race, ethnicity, and socioeconomic status from the National Cancer Database.

e16385 Background: Gallbladder neuroendocrine tumors (NETs) are exceedingly rare tumors and carry a poor prognosis. Racial/ethnic disparities and socioeconomic status have been known to influence cancer treatment and outcomes. This study explores racial/ethnic and socioeconomic disparities in treatment patterns of primary gallbladder NETs, focusing on factors affecting receipt of chemotherapy and multimodal therapy. Methods: We analyzed primary gallbladder NETs patients using the National Cancer Database (NCDB) from 2004 to 2020. Racial groups were divided into White and Black categories, and then those groups were further divided into Hispanic White, non-Hispanic White, Hispanic Black, and non-Hispanic Black categories according to ethnicity. We considered socioeconomic factors, tumor histology, and facility type. Logistic regression was used to determine the odds of receiving chemotherapy and multimodality therapy. The significance of disparities was determined using odds ratio (OR) and p-value. Results: Of 1,195 primary gallbladder NET patients, 59% (708 patients) underwent surgery. These patients had a median age of 65 years, with a female majority (64%) and predominantly White ethnicity (73.6%). Insurance coverage varied, with 48.9% having Medicare and 35.6% private insurance, while 3.9% were uninsured and 8.6% were covered by Medicaid. The study highlighted key factors affecting the receipt of surgery. Notably, racial disparities were apparent, with Black patients less likely to receive surgery compared to White patients (OR: 0.52; P < .001). Furthermore, patients with typical carcinoid tumors were markedly more likely to receive surgery than those with other histology (OR: 10.93; P < .001). The type of treatment facility was influential, with patients in Academic/Research Programs more likely to receive surgery (OR: 0.41; P < .001) than those in Community Cancer Programs. Conclusions: This study highlights racial and socioeconomic disparities in chemotherapy and multimodality therapy for gallbladder NETs, with Black, uninsured, and Medicaid-insured patients less likely to receive treatment. These findings call for targeted policy and healthcare reforms to ensure equitable access and outcomes for all patients with this condition. [Table: see text]

CT and MRI Imaging Features and Diagnosis of Gallbladder Neuroendocrine Tumors

CT and MRI Imaging Features and Diagnosis of Gallbladder Neuroendocrine Tumors

Neuroendocrine neoplasms of the gallbladder: early detection and surgery is key to improved outcome.

Neuroendocrine neoplasms (NENs) of the gallbladder are very rare. As a result, the classification of pathologic specimens from gallbladder NENs, currently classified as gallbladder neuroendocrine tumors (GB-NETs) and carcinomas (GB-NECs), is inconsistent and makes nomenclature, classification, and management difficult. Our study aims to evaluate the epidemiological trend, tumor biology, and outcomes of GB-NET and GB-NEC over the last 5 decades. This is a retrospective analysis of the SEER database from 1973 to 2016. The epidemiological trend was analyzed using the age-adjusted Joinpoint regression analysis. Survival was assessed with Kaplan-Meier analysis and Cox regression was used to assess predictors of poor survival. A total of 482 patients with GB-NEN were identified. Mean age at diagnosis was 65.2 ± 14.3years. Females outnumbered males (65.6% vs. 34.4%). The Joinpoint nationwide trend analysis showed a 7% increase per year from 1973 to 2016. The mean survival time after diagnosis of GB-NEN was 37.11 ± 55.3months. The most common pattern of nodal distribution was N0 (50.2%) followed by N1 (30.9%) and N2 (19.2%). Advanced tumor spread (into the liver, regional, and distant metastasis) was seen in 60.3% of patients. Patients who underwent surgery had a significant survival advantage (111.0 ± 8.3 vs. 8.3 ± 1.2months, p < 0.01). Cox regression analysis showed advanced age (p < 0.01), tumor stage (P < 0.01), tumor extension (p < 0.01), and histopathologic grade (p < 0.01) were associated with higher mortality. Gallbladder NENs are a rare histopathological variant of gallbladder cancer that is showing a rising incidence in the USA. In addition to tumor staging, surgical resection significantly impacts patient survival, when patients are able to undergo surgery irrespective of tumor staging. Advanced age, tumor extension, and histopathological grade of the tumor were associated with higher mortality.

Abstract 2253: Comparison of genomic alterations in neuroendocrine tumors originated from different primary sites

Abstract Background: Neuroendocrine tumors (NETs) are heterogeneous, relatively rare tumors derive from neuroendocrine system. Currently, limited therapeutic strategies are available for NETs. Next-generation sequencing (NGS) and target gene-based precision therapy have shown promising efficacy in many tumors, but fare in NETs. Several reports illustrated that the primary sites of NETs were significantly bound up with the clinical response and prognosis. However, characteristics of their genomic alterations are insufficiency nowadays. Methods: A cohort of 94 Chinese NET patients were recruited, and the FFPE tumor tissues and matching blood samples from different primary sites were collected. Targeted next generation sequencing (NGS) of 450 genes was performed in OrigiMed (Shanghai, China) with a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: In all patients, the top 5 most-frequently aberrant genes were TP53 (46.8%, 44/94), RB1 (23.4% 22/94), MEN1 (20.2%, 19/94), KRAS (11.7%, 11/94) and ATRX (9.6%, 9/94). The enrolled NETs contain 7 different primary sites, namely, 37 pancreatic NETs (PNETs), 16 hepatic NETs (HNETs), 11 gastric NETs (GNETs), 10 gallbladder NETs (GB-NETs), 8 esophageal NETs (ENETs), 7 colorectal NETs (CNETs), and 5 small intestine NETs (SI-NETs). Based on origin sites, TP53 is the most widely distributed mutant gene in all sites except for PNETs (Ranked 3rd), while RB1 mutations were significantly higher in ENETs (75.0%, 6/8), GB-NETs (60.0%, 6/10) and GNETs (36.4%, 4/11). Other higher -frequency mutated genes among different sites showed greatly dissimilarity (MEN1, ATRX and DAXX in PNETs; FAT3, MAX, MUC16, GATA4 and OBSCN in HNETs; APC, KRAS and PTEN in GNETs; TERT, ERBB2 and YES1 in GB-NETs; LRP1B and FBXW7 in ENETs; APC, ADGRA2 and FGFR1 in CNETs; NF1 in SI-NETs). Furthermore, signaling pathways involved in potential drug-target genes were analyzed. Results revealed 16.0% (15/94) patients with aberrations in PI3K/AKT/mTOR pathway, 11.7% (11/94) in Cell-Cycle pathway, 9.6% (9/94) in HRD pathway, 9.6% (9/94) in FGF pathway and 16.0% (15/94) in other cancer-related genes (ERBB2, VHL, MET etc.). Conclusions: This study reveals the genomic alteration characteristics of NETs from different primary sites. The profiles obtained in our study may provide evidences for further targeted therapy to improve outcomes of Chinese NETs. Citation Format: Qiyun Tang, Ye Tian, Xiaolin Li, Jian'an Bai, Min Liu, Ping Hu, Shanshan Zhang, Zanmei Xu, Yueting Qu, Aodi Wang. Comparison of genomic alterations in neuroendocrine tumors originated from different primary sites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2253.

Differential and prognostic MRI features of gallbladder neuroendocrine tumors and adenocarcinomas.

To identify MRI features that are helpful for the differentiation of gallbladder neuroendocrine tumors (GB-NETs) from gallbladder adenocarcinomas (GB-ADCs) and to evaluate their prognostic values. Between January 2008 and December 2018, we retrospectively enrolled patients who underwent MRI for GB malignancy. Two radiologists independently assessed the MRI findings and reached a consensus. Significant MRI features, which distinguish GB-NETs from GB-ADCs, were identified. Cox regression analyses were performed to find MRI features that were prognostic for overall survival. There were 63 patients with GB-NETs (n = 21) and GB-ADCs (n = 42). Compared with GB-ADCs, GB-NETs more frequently demonstrated the following MRI features: well-defined margins, intact overlying mucosa, and thick rim contrast enhancement and/or diffusion restriction (ps < 0.001). Liver metastases were more common and demonstrated thick rim contrast enhancement and diffusion restriction in GB-NETs (ps < 0.001). Lymph node (LN) metastasis showed thick rim diffusion restriction more often in GB-NETs than in GB-ADCs (p = 0.009). On quantitative analysis, the sizes of the GB mass and metastatic LNs in GB-NETs were larger than those in GB-ADCs (p = 0.002 and p = 0.010, respectively). The ratio of apparent diffusion coefficient values between the lesion and the spleen was lower in the GB mass, liver metastases, and LN metastases of GB-NETs than those of GB-ADCs (p < 0.001, p = 0.017, and p < 0.001, respectively). Survival analysis revealed that a large metastatic LN (hazard ratio 1.737; 95% confidence interval, 1.112-2.712) was the only poor prognostic factor (p = 0.015). Several MRI features aided in differentiating between GB-NETs and GB-ADCs. A large metastatic LN was associated with poor survival. • Compared with gallbladder adenocarcinomas (GB-ADCs), neuroendocrine tumors (GB-NETs) and their metastases to the liver and lymph nodes more frequently demonstrated a thick rim appearance on contrast-enhanced MRI and diffusion-weighted images. • The ratio of apparent diffusion coefficient values between the lesion and the spleen was significantly lower for the primary mass, liver metastases, and lymph node metastases of GB-NETs than for those of GB-ADCs. • A large metastatic lymph node was the only poor prognostic factor for overall survival in patients with GB-NETs and GB-ADCs.

The nationwide rising incidence of neuroendocrine tumor of the gallbladder: Predictors of mortality

Presenter: Shekhar Gogna MD | Westchester Medical Center Background: Primary gallbladder neuroendocrine tumors (GB - NET) are very rare. Although there are other numerous studies of neuroendocrine tumors, few case series describing primary GB-NET exist. Methods: This is a retrospective analysis of the SEER database from 1973 – 2016. The epidemiological trend was analyzed using the Joinpoint regression analysis. Survival was assessed with Kaplan-Meier analysis and Cox-regression was used to assess predictors of poor survival. We also utilized the artificial neural network to assess the discriminatory power of significant variables on Cox regression and to assess the individual variable important in predicting survival. Results: A total of 329 patients with GB-NET were identified from the SEER database. The mean age at diagnosis was 65.39 ± 14.32 years. Females outnumbered males (66.3 % vs. 33.7 %) and whites were the predominant race included (79.6 %). The Joinpoint nationwide trend analysis shows a rising trend of this tumor pathology by 7 % per year from 1973 to 2016 (Figure I). The mean survival time after diagnosis of GB-NET was 43.11 ± 58.80 months (0 – 239 months). The most common pattern of nodal metastasis pattern was N0 (57.1 %), followed by N2 (15.8 %), and N1 (10.7 %), with survival mirroring nodal status (p <0.01). Patients who underwent surgery had a significant survival advantage (105.50 ± 6.93 months compared with 7.32 ± 1.53 months, p<0.01). Cox- regression analysis showed advanced age (HR 1.03, p<0.01), tumor extension (HR 5.16, P < 0.01) and histopathological grade (HR 3.15, P < 0.01) of the tumor being associated with higher mortality. The artificial neural network model showed that the tumor grade had the highest predictor for mortality. Conclusion: GB-NET is a rare histopathological type of gallbladder cancer, that is displaying a rising incidence in the US. The high incidence of localized disease in simple cholecystectomy specimens suggests that discovery after gallbladder surgery may be contributing to the rising histological identification. Surgical resection is associated with a significant survival advantage. Advanced age, tumor extension and histopathological grade of the tumor are associated with higher mortality.

Polypoid gallbladder neuroendocrine tumor diagnosed as benign polyp before surgery: A case report.

Gallbladder neuroendocrine tumors (GB-NETs) comprise only 0.5% of all NET cases, and their biology has been incompletely characterized. In the present study we report the case of a 50-year-old male patient with GB-NET who was admitted to Naito Hospital with diarrhea as the main complaint. At initial diagnosis, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range. Abdominal ultrasonography and contrast-enhanced computed tomography (CT) revealed gallbladder adenomyomatosis and cholecystitis, and an 8-mm pedunculated polypoid lesion was found in the neck of the gallbladder using drip infusion cholecystocholangiography-CT. As it was considered a benign polyp, laparoscopic cholecystectomy was performed. Pathological examination revealed a polypoid lesion that comprised NET cells with a cord-like or ribbon-like arrangement, and the cells exhibited positive immunostaining for chromogranin A and synaptophysin. In addition, immunohistochemical staining showed a Ki-67 index (i.e., proliferation index) of <1%, and no necrosis or mitotic figures were observed in the background. Based on these observations, we diagnosed the following: GB-NET, G1, 10x12 mm in size and located in the gallbladder neck. According to the World Health Organization 2010 classification, NET G1 is a well-differentiated tumor, with the tumor cells having a low proliferative potential [Ki-67 index ≤2%; mitotic figure number <2 (/10 HPF)]. It is regarded as a low- to mild-grade malignancy. Low-grade GB-NET occurs relatively rarely, and no clear guidelines have been formulated regarding its surgical treatment, such as minimal surgical excision margins or lymph node dissection. Detailed treatment recommendations should be developed after systematic studies of additional cases of GB-NET.

Primary Gallbladder Neuroendocrine Tumors: Insights into a Rare Histology Using a Large National Database.

Primary gallbladder neuroendocrine tumors (NETs) are rare, poorly understood cancers infrequently encountered at even the largest of tertiary referral centers. We therefore sought to identify a large cohort of patients with gallbladder NETs using a national database, with the aim of defining treatment modalities employed and survival associated with these uncommon malignancies. Patients with primary gallbladder NETs were identified in the National Cancer Database, and clinicopathologic characteristics were recorded. A univariate log-rank survival analysis was completed for patients who underwent resection. Parameters found to be significant were entered into a multivariate accelerated failure time analysis. For context, survival comparisons were included for patients who underwent resections for NETs at any gastrointestinal site and for gallbladder adenocarcinoma. Overall, 754 patients with gallbladder NETs were identified. Patients were predominantly female (n = 518, 69%), White (n = 503, 67%), presented with stage IV disease (n = 295, 39%) and had high-grade lesions (n = 312, 41%). The majority underwent resection (n = 480, 64%), primarily simple cholecystectomy (n = 431, 90%), whereas a minority received multimodal therapy (n = 145, 21%). Among patients who underwent resection, older age (p = 0.001), large cell histology (p = 0.012), and positive margins (p = 0.030) were independently associated with worse overall survival. Patients with gallbladder NETs had improved survival relative to those with gallbladder adenocarcinoma (p = 0.001), but significantly worse survival than patients with NETs from other gastrointestinal sites (p < 0.001). Primary gallbladder NETs are aggressive lesions that carry a worse prognosis than NETs of other gastrointestinal sites. Older age, positive margins, and large cell histology are associated with abbreviated survival after resection.

Neuroendocrine Carcinoma of Gallbladder: A Step Beyond Palliative Therapy, Experience of 25 Cases

Published literature on gall bladder neuroendocrine tumors (GB NETs) is limited with none reporting the role of multimodal therapy. Patients with histologically confirmed GB NETs treated at Tata Memorial Hospital, Mumbai, from January 2010 to June 2017 were analyzed. Staging was done by contrast-enhanced computed tomography (CECT) of abdomen and chest or a positron emission topography (PET) scan. Tumor marker (CA19-9) was measured. WHO-2017 guideline was used to classify GB NETs. GB NETs were categorized as early disease (ED) (T1, T2, N0, i.e., stages I and II); locally advanced disease (LAD) (T3, T4, or N+, i.e., stage III); and metastatic disease (MD). Response to treatment was assessed with RECIST1.1 criteria. Twenty-five patients of GB NETs were identified; 19 with neuroendocrine carcinomas (NECs) and 6 with mixed adenoneuroendocrine carcinomas (MANECs). Two patients (8%) presented with ED, 9 (36%) with LAD, and 14 (56%) had MD. Those with ED underwent open revision radical cholecystectomy. Both received adjuvant chemotherapy (ACT) with six cycles of carboplatin-etoposide and were disease-free at 3months of follow-up. Of the nine patients with LAD, six received three cycles of neoadjuvant chemotherapy (NACT) (carboplatin-etoposide) and three operated upfront. All six patients showed partial response to NACT and five underwent open radical cholecystectomy with R0 resection. All patients operated after NACT received three cycles of ACT. Their median follow-up was 7months (range 3-22months). Three patients with LAD developed metastasis after median disease-free survival of 5months. The median survival in patients with MD was 12 (range 6-23) months. In carefully selected patients of GB NECs, downsizing with NACT facilitates radical resection with negative margins.

Outcome and CT differentiation of gallbladder neuroendocrine tumours from adenocarcinomas.

To retrospectively investigate clinical outcome and differential CT features of gallbladder (GB) neuroendocrine tumours (NETs) from adenocarcinomas (ADCs). Nineteen patients with poorly-differentiated (PD) NETs and 19 patients with PD ADCs were enrolled. Clinical outcome was compared by the Kaplan-Meier method. We assessed qualitative and quantitative CT features to identify significant differential CT features of PD NETs from ADCs using univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was used for quantitative CT features. PD NETs showed poorer prognosis with significantly shorter median survival days than ADCs (363 vs. 590days, P = 0.03). On univariate analysis, NETs more frequently manifested as GB-replacing type and showed well-defined margins accompanied with intact overlying mucosa. On multivariate analysis, well-defined margin was the sole significant CT differentiator (odds ratio = 27.817, P = 0.045). Maximum size of hepatic and lymph node (LN) metastases was significantly larger in NETs (11.0cm and 4.62cm) than ADCs (2.40cm and 2.41cm). Areas under ROC curves for tumour-to-mucosa ratio, maximum size of hepatic and LN metastasis were 0.772, 0.932 and 0.919, respectively (P < 0.05). GB PD NETs show poorer prognosis than ADCs. Well-defined margin, larger hepatic and LN metastases are useful CT differentiators of GB NETs from ADCs. • A well-defined margin is a useful CT differentiator of GB NETs from ADCs. • Hepatic and LN metastases are significantly larger in NETs than in ADCs. • Primary tumour and hepatic metastasis of NETs are more hyperattenuated than ADCs.

P-137 Clinical feature of 53 patients with biliary neuroendocrine tumors: Retrospective study for Korean neuroendocrine tumor of gallbladder, extrahepatic biliary tract, and ampulla of Vater

P-137 Clinical feature of 53 patients with biliary neuroendocrine tumors: Retrospective study for Korean neuroendocrine tumor of gallbladder, extrahepatic biliary tract, and ampulla of Vater

Cytomorphology of neuroendocrine tumours of the gallbladder.

Gallbladder neuroendocrine tumours (GB-NETs) are rare and account for 0.5% of all NETs. GB-NETs have an aggressive behaviour, which depends on the tumour grade. The cytomorphological spectrum of these tumours has never been described in detail. The present study evaluates the cytological features of GB-NETs and grades them according to the World Health Organization (WHO) classification. Furthermore, the expression of thyroid transcription factor-1 (TTF-1) has not been investigated previously in GB-NETs, although found in a subset of extrapulmonary NETs. Twenty cases of GB-NET among 875 gallbladder carcinomas diagnosed by ultrasound-guided fine needle aspiration cytology (FNAC) over a period of nearly 4years were studied. The following parameters were evaluated: architectural pattern, nuclear chromatin, nucleoli, mitoses, necrosis, moulding, apoptosis and smudge cells. Cases were categorized into well-differentiated (grades 1 and 2), small cell carcinoma (SCC) (grade 3) and mixed adenoneuroendocrine carcinoma. Nuclear positivity for TTF-1 was considered as positive. Morphologically, tumour cells were mainly arranged in rosettes in the well-differentiated category; sudden anisonucleosis and rare nuclear moulding with or without mitotic figures were other features. Eleven cases of SCC showed prominent nuclear moulding with frequent smudge cells, mitoses, apoptosis and necrosis. Three mixed adenoneuroendocrine carcinomas showed papillary fragments and an acinar arrangement of tumour cells. Four of the nine SCCs in which TTF-1 was evaluated on de-stained smears showed nuclear positivity. Histopathology was available in two SCCs and showed morphology similar to FNAC. Cytology plays an important role in the diagnosis of GB-NETs for appropriate subtype characterization, which is necessary for the prognostication of these tumours. TTF-1 may not be used for the differentiation of gallbladder SCCs from pulmonary SCCs.

Gallbladder: A rare primary site for small cell carcinoma

Neuroendocrine tumors (NETs) are an extremely rare entity in gallbladder (GB), occurring in approximately 0.5% cases of NETs from all sites. In the present case report, a 42-year-old male presented with recurrent right upper quadrant pain for 2 months. Abdominal ultrasound revealed a small nodular swelling in the GB. On aspiration cytology that appeared as individual small tumor cells mostly in dispersed population and frequent nuclear molding within cell aggregates in a necrotic background. The patient was diagnosed as NET of GB. Histopathology revealed; uniform small rounded cells arranged in peritheliomatous pattern with intervening areas of massive necrosis. Nuclear molding, salt-pepper nuclear chromatin and frequent mitoses were also evident. Immunohistochemistry with chromogranin confirmed the diagnosis of small cell carcinoma.

Tu1908 Survival Outcomes and Clinicopathologic Characteristics of Primary Gallbladder Neuroendocrine Tumors

Tu1908 Survival Outcomes and Clinicopathologic Characteristics of Primary Gallbladder Neuroendocrine Tumors

Neuroendocrine tumor of gallbladder: a case report in maharaj nakorn chiang mai hospital

Introduction Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) originate from neuroendocrine cells which distribute along the entire gastrointestinal tract and pancreas. The site of predilection is the stomach and the tumors are mostly graded as G1 NETs; however, gallbladder NETs are extremely rare, showing only 0.5% of all NETs with unfavorable prognosis. Case presentation A 68-year-old woman underwent open cholecystectomy for symptomatic gallstones, and the gallbladder was diagnosed as poorly differentiated adenocarcinoma. Two months later, two liver metastases were detected in segment 4a and 5. Hepatic segmentectomy (segment 4a and 5) was done. The liver pathology revealed infiltration of small round tumor cells containing small nuclei with fine granular chromatin and inconspicuous nucleoli. The tumor cells were immunoreactive for chromogranin A; therefore, metastatic small cell carcinoma was diagnosed. The gallbladder lesion was reviewed and the diagnosis was revised to neuroendocrine carcinoma grade 3. The patient was sent to the provincial hospital for further chemotherapeutic treatment. Conclusion Neuroendocrine tumors of gallbladder are uncommon and indistinguishable from carcinoma of gallbladder clinically and surgically. Features from radiographic investigation and histopathological features are essential for making the diagnosis. Moreover, the prognosis of gallbladder neuroendocrine tumor is poor and the 5-year survival rate is worse than neuroendocrine tumor from other locations.

Neuroendocrine Neuroendocrine carcinoma of gallbladder: A rare case report

Primary neuroendocrine carcinoma of gallbladder is extremely rare, representing 0.2% of all neuroendocrine tumors, as normal gallbladder mucosa does not contain neuroendocrine cells. Little is known about its biological behavior. Diagnosis is incidental in most of the cases. We sought to give an overview of the current state of knowledge about gallbladder neuroendocrine tumors. We describe the case of a 55-year-old man who underwent cholecystectomy for the evaluation of a gallbladder mass that had been incidentally detected by ultrasonography. Histologically, the lesion was composed of monomorphic cells that contained round nuclei and were organized in small nests, nodules, trabeculae, and acini. Cells were positive for chromogranin A and a diagnosis of neuroendocrine carcinoma of the gallbladder was made. He is disease-free 8 months after surgical treatment. Characteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis. The biological behavior of the tumor is still not well defined. Thus, reporting every case is important and may contribute to the existing knowledge regarding the behavior and management of this rare tumor.

Neuroendocrine tumors of the gallbladder: a case report and review of the literature

IntroductionPrimary gallbladder neuroendocrine tumors are extremely rare, representing 0.2% of all neuroendocrine tumors. The diagnosis is incidental in most cases.Case presentationWe describe the case of a 57-year-old Caucasian man who underwent laparoscopic cholecystectomy for the evaluation of a gallbladder polyp that had been incidentally detected by ultasonography. Histologically, his lesion was composed of monomorphic cells that contained small round nuclei and that were organized in small nodular, trabecular, and acinar structures. His cells were positive for chromogranin A and synaptophysin, and a diagnosis of "typical" carcinoid of the gallbladder was made. His post-operative computerized axial tomography, 111In-pentetreotide scintigraphy, and hormone-specific marker results were negative. He is disease-free 45 months after surgical treatment.ConclusionsCharacteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Whereas classical carcinoids of the gallbladder only rarely have a metastatic or invasive phenotype, the "atypical" variants are more aggressive and are associated with a poorer prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to consider each polypoid-like lesion of the gallbladder to be a high-risk lesion if it is larger than 1 cm and, as a result, to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis.

Neuroendocrine Tumors of the Gallbladder

Gallbladder neuroendocrine tumors (GB-NETs) represent only 0.5% of all NETs, and little is known about their biological behavior. We sought to provide an overview of the current state of knowledge about GB-NETs and provide a recommendation for management. A PubMed search was undertaken using the following criteria: primary gallbladder and carcinoid or NET. We also interrogated the SEER 9, 13 and 17 registries (1973 to 2005) and the Niigata registry (2003) to assess the epidemiology and clinicopathological characteristics. Finally, we compared the clinical presentation, management and prognosis of GB-NETs to that of gallbladder adenocarcinoma. GB-NETs probably derive from either a multipotent stem cell or neuroendocrine cells in intestinal or gastric metaplasia of the gallbladder epithelium, which occurs consequent upon cholelithiasis/chronic inflammation. Clinically and at surgery, GB-NETs are indistinguishable from gallbladder cancer (GBC) and "carcinoid syndrome" is evident in only ∼1%.The median survival was only 9.8 months among 278 cases of GB-NETs reported in SEER. The 5 year survival rate for tumors classified as carcinoids/neuroendocrine carcinoma or small cell cancer (SCC) was 36.9 and 0%, respectively. Soga divided GB-NETs into typical and variant carcinoids with 5 year survival rates of 60.4% and 21.3% respectively. GB-NETs have an aggressive behavior, and once diagnosed, extensive surgical management and careful NET follow up with CT scan is mandatory to facilitate early detection of recurrence. Since more aggressive surgical management for GBC has shown increased survival rates for these tumors, a similar strategy seems reasonable for GB-NETs. However, in high grade metastatic tumors, the primary management is mainly medical.