Ampullary Neuroendocrine Tumors Research Articles

Can Ampullary G1 and G2 Neuroendocrine Tumors Be Cured by Endoscopic Papillectomy?

At present, pancreaticoduodenectomy or local excision are the main treatment options for ampullary neuroendocrine tumors of any size with no distant spread. Endoscopic papillectomy provided a super minimally invasive treatment method for ampullary lesions. However, the studies of endoscopic papillectomy for ampullary neuroendocrine tumors were very limited. This study aimed to assess the feasibility of endoscopic papillectomy for ampullary neuroendocrine tumors. Between August 2007 and June 2021, seven patients with ampullary neuroendocrine tumors with no advanced signs underwent endoscopic papillectomy in our center. We assessed and analyzed the related clinical outcomes. Moreover, a comprehensive literature review was conducted. All the seven cases underwent endoscopic papillectomy successfully; six (85.7%) of them achieved the complete resection. No recurrence occurred over a median follow-up of 48 months (range 6-172 months). Moreover, 22 cases from the comprehensive search were included, and showed a promising clinical outcome. Endoscopic papillectomy appeared to be a feasible way to treat ampullary neuroendocrine tumors without the advanced signs, although further prospectively multicenter studies are warranted.

Robot assisted transduodenal ampullectomy for neuroendocrine tumor

Background: Ampullary neuroendocrine tumors (NET) are a rare entity representing less than 1% of all gastroenteropancreatic NETs. While small, well differentiated tumors have a low propensity for lymph node and distant metastasis, the unique location at the ampulla carries the risk of subsequent biliary obstruction.

Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases

Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.

Ampullary Neuroendocrine Tumors: A Window into a Rare Tumor

Background: Ampullary neuroendocrine tumors (NETs) make up <1% of all gastroenteropancreatic NETs and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs.

Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n=149, 17%) than patients with duodenal (n=197, 2%) or pancreatic head (n=740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n=297, 34%) than patients with duodenal (n=950, 10%) or pancreatic head (n=1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p<0.0001), Charlson-Deyo score of 2 (HR 2.3, p=0.001) or ≥3 (HR 2.9, p=0.013), grade 2 (HR 1.9, p=0.007) or grade 3 tumors (HR 4.0, p<0.0001), and metastatic disease (HR 2.0, p=0.001) were associated with decreased survival. At 5years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p<0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p<0.0001). Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

ASO Visual Abstract: Ampullary Neuroendocrine Tumors—Insight into a Rare Histology

Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs. \Our study uses a national database to evaluate clinicopathologic factors and overall survival of this rare tumor ( https://doi.org/10.1245/s10434-021-10371-w ). It demonstrates that ampullary NETs likely have a different underlying biology than duodenal and pancreatic head NETs.

Abstract 611: Colibactin mutation signatures are associated with a distinct colorectal cancer clinicopathologic phenotype

Abstract PURPOSE: Alterations in the gut microbiome contribute to colorectal cancer (CRC) pathogenesis. The genotoxin colibactin, produced by pks+ E. coli, directly binds to DNA, leaving genetic scars at A-T rich motifs that can be identified by whole genome/exome sequencing (WGS/WES) as hexanucleotide mutation signatures SBS28 and SBS41. Here, we investigated whether MSK-IMPACT, a clinical targeted exon capture assay with lower genomic coverage (341-468 cancer associated exons), could be used to identify colibactin mutation signatures (CMS) and provide insight into associated clinicopathologic phenotypes. METHODS: From an institutional pan-cancer cohort of 36,158 tumors assayed using MSK-IMPACT, we identified 11,864 samples (1,386 CRC) with at least 20 mutations and applied TempoSig, an algorithm which uses maximum likelihood-based extraction of mutational signature proportions. Tumors with at least 10% of all mutations attributed to SBS28/41 were deemed CMS+. Due to the association of POLE mutations and microsatellite instability with distinct phenotypes, we excluded these cases from our analysis. RESULTS: Consistent with prior reports based on WGS/WES, our MSK-IMPACT TempoSig pipeline identified CMS positivity in multiple cancers, notably gastrointestinal (GI) and head and neck cancers. Ampullary tumors (25%) and GI neuroendocrine tumors (8%) had the highest SBS28 and SBS41 positivity respectively. Among microsatellite stable CRCs, we identified 52 patients with at least one sample positive for SBS28 (N=25) or SBS41 (N=27). Compared with CMS negative tumors, SBS28+ but not SBS41+ tumors had higher chromosomal instability as quantified by fraction of the genome altered by copy number alterations (SBS28+: 33.4% vs. SBS28-: 22.3%, P&amp;lt;.01), lower tumor mutation burden (SBS28+: 7.9/Mb vs. SBS28-: 8.8/Mb, P=.011), and a trend toward younger median age at sampling (57 (IQR 46-66) vs. 61 (IQR 51-70), P=.095). SBS28+ tumors harbored more frequent mutations in DNA damage repair (DDR) genes ATR (7.1 vs. 0.5%, P=.02) and ATM (14.3 vs. 4.1%, P=.03). Overall survival from diagnosis was decreased in patients with SBS28+ compared with SBS41+ tumors (22.0 vs. 43.7 months, P&amp;lt;.07), regardless of initial stage (P&amp;lt;.01). Histopathology revealed increased TILs in 13% of evaluable SBS28+ and 7% of SBS41+ tumors, while RNA FISH using a probe targeting the clbP gene required for colibactin synthesis was negative in all CMS+ samples, suggesting that colibactin mutagenesis is an early event not requiring persistent pks+ E. coli colonization. CONCLUSIONS: TempoSig enables rigorous identification of colibactin mutation signatures in clinically utilized MSK-IMPACT targeted exon datasets. SBS28+ CRCs are clinically distinct and associated with early onset, poor prognosis and DDR pathway alterations. In ongoing studies, we are investigating the therapeutic implications of these findings. Citation Format: Melissa A. Lumish, Anisha Luthra, Simran Asawa, Francesco Cambuli, Mark Donoghue, Hyung Jun Woo, Andrea Cercek, Rona Yaeger, Jinru Shia, Francisco Sanchez-Vega, Karuna Ganesh. Colibactin mutation signatures are associated with a distinct colorectal cancer clinicopathologic phenotype [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 611.

Ampullary neuroendocrine tumors: A window into a rare tumor using a national database.

373 Background: Ampullary neuroendocrine tumors (NET) make up &lt; 1% of all gastrointestinal NETs. Information about their behavior and prognosis is reliant on small case series. This study set out to describe the population of patients who are diagnosed with ampullary NETs and compare them to patients with duodenal and pancreatic head NETs. Methods: The National Cancer Database (2004 – 2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Clinicopathologic and treatment characteristics were compared. Subset analysis was performed on patients who underwent surgery. Kaplan Meier (KM) analysis and Cox regression were used to analyze the survival of patients with ampullary NETs. Results: Overall, 872 patients were identified with ampullary NET, 9692 with duodenal NET, and 6562 with pancreatic head NET. Patients with ampullary NET had an average age of 60.9 +/- 14.5 years, were evenly split among men and women (N = 437, 50.1% vs N = 435, 49.9%, respectively), and primarily Caucasian (N = 663, 76.0%). 72.1% underwent local tumor destruction or surgery (N = 629). Most did not receive radiation (N = 832, 95.4%), chemotherapy (N = 627, 71.9%), or hormone therapy (N = 788, 90.4%). Patients with ampullary NETs had more poorly differentiated tumors (N = 119, 13.6%) than patients with duodenal (N = 159, 1.6%) or pancreatic head (N = 602, 9.2%) NETs. Patients with ampullary NETs had more positive lymph nodes (N = 288, 33%) than patients with duodenal (N = 915, 9.4%) or pancreatic head (N = 1381, 21%) NETs. At five years, the overall survival for patients with ampullary, duodenal, and pancreatic head NETs was 57%, 68%, and 46%, respectively. Within the surgical population, five-year survival for patients with ampullary (N = 367), duodenal (N = 991), and pancreatic head (N = 1961) NETs was 60%, 74%, and 72%, respectively. When compared, there was a statistically significant difference between the mean overall survival of patients with ampullary (98 +/- 4.7 months), duodenal (112 +/- 2.5 months), and pancreatic head (108 +/- 1.7 months) NETs (p &lt; 0.001). In the cox regression analysis, sex, Charlson-Deyo score, lymph node positivity, lymph-vascular invasion, mitotic rate, chromogranin A level, 5-HIAA level, and tumor size did not correlate with survival. Increasing age (HR 1.04, CI 1.01 – 1.07, p = 0.008) and worse tumor differentiation (poorly differentiated HR 3.33, CI 1.38 – 8.04, p = 0.008 and undifferentiated HR 8.31, CI 2.77 – 24.92, p &lt; 0.001 compared to well differentiated) were associated with increased mortality. Conclusions: This study sheds light on a rare tumor histology. When compared to patients who underwent surgical resection for duodenal or pancreatic head NETs, patients with ampullary NETs had a significantly worse prognosis. Identifying prognostic factors allows us to create more concrete treatment recommendations and provide patients with improved prognostic information.

Treatment of ampullary neuroendocrine tumor by Capecitabine (Xeloda®) and Temozolomide (Temodal®).

Neuroendocrine tumors of the gastrointestinal tract and pancreas include a range of rare and diverse neoplasms with unique tumor biology, natural history, and clinical management. Neuroendocrine tumors of the ampulla of Vater are extremely uncommon cancers that account for only about 0.3%-1% of all gastrointestinal neuroendocrine tumors. Approximately 139 cases have been reported to date. In this paper, we describe two patients with low to intermediate grades of ampullary neuroendocrine tumors that underwent multiple courses of chemotherapy with Capecitabine (Xeloda®) and Temozolomide (Temodal®). Our two patients had a dramatic response to this regimen.According to our study, it seems that ampullary neuroendocrine tumors have behavior like pancreatic neuroendocrine tumors which requires further studies in more patients.

Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin.

Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.

2651 Secrets of the Ampulla: A Rare Neuroendocrine Tumor

INTRODUCTION: Neuroendocrine tumors (NETs) of the ampulla of Vater represent less than 0.3% of gastrointestinal NETs and less than 2% of all periampullary malignancies. There are approximately 139 cases in literature, making this rare condition a diagnostic challenge. Jaundice is the predominant symptom followed by abdominal pain. Acute pancreatitis as the initial presentation has seldom been reported. Herein we report a case of a patient who presented with acute pancreatitis and biliary obstruction secondary to an ampullary NET. CASE DESCRIPTION/METHODS: Case of a 74-year-old male with hypertension who reported burning epigastric pain. Denied fever, vomits, weight loss, diarrhea, flushing or dyspnea. Physical examination with epigastric tenderness. Laboratories showed elevated alkaline phosphatase 398 U/L, total bilirubin 3.4 mg/L, lipase 594 U/L and amylase 216 U/L. Contrast abdominopelvic CT showed a duodenal periampullary mass with common bile duct measuring 1.1 cm and intrahepatic and extrahepatic dilatation. Endoscopic retrograde cholangiopancreatography (ERCP) revealed an irregular, ulcerated ampullary mass. Biopsy showed poorly differentiated carcinoma. Immunostains were positive for chromogranin, synaptophysin, CK7, weakly positive for CDX-2. Negative for TTF-1 and CK20. Octreotide scintigraphy with no uptake. Somatostatin, chromogranin, and 5-hydroxy-in-dole acetic acid were normal. Patient underwent surgical treatment with pancreaticoduodenectomy. DISCUSSION: The rarity of ampullary NETs and its proliferation under an intact mucosa makes it difficult to detect in biopsy. Most of the time the diagnosis is based on histology and preoperative diagnosis may be challenging since they clinically present like adenocarcinoma. The usual presentation of jaundice and abdominal pain places this diagnosis low on the differential. In our case, the unusual morphologic appearance likely facilitated obtaining an assertive pre-operative diagnosis. Our patient presented with obstructive jaundice and acute pancreatitis, which occurs in less than 6% of cases. The clinical picture of ampullary NETs is easily confounded given the associated symptoms and biopsy challenges. A high index of suspicion is paramount to ensure this rare diagnosed is not missed. Pancreaticoduodenectomy has been advocated as the treatment of choice regardless of size due to high risk of occult nodal metastases. Considering this diagnosis within the differential is important given the drastically different outcomes for patients if caught early.

Carcinoids of the ampulla: Long-term follow-up after endoscopic resection.

430 Background: Neuroendocrine tumors (NET) or carcinoids of the ampulla are exceedingly rare in comparison to duodenal NET. Surgical management is widely accepted as the treatment of choice, but for patients that refuse surgery or are poor operative candidates, endoscopic resection may be option. We present a consecutive case series at a tertiary care center describing our experience with endoscopic resection of ampullary NET. Methods: This is a restrospective review with a long-term follow-up of patients with ampullary NET that were endoscopically resected. Outcomes were analyzed based on the histopathologic classification system proposed by the World Health Organization in 2000. Results: Twelve patients (9 male, 3 female), ranging in age from 41 to 86 (mean 59) underwent endoscopic ampullectomy for ampullary NET, with a mean follow-up time of 5 years. Patients had refused surgery or were poor surgical candidates. All, but one incidentally found case, were symptomatic on presentation, with gastrointestinal bleeding being the main symptom. No patients had a hormonal syndrome. The mean size of the lesions was 21 mm (6 mm to 35 cm). Six (50%) patients had a well-differentiated, benign lesion, 6 (50%) patients had a well-differentiated NET with unknown malignant potential (gangliocytic paragangliomas). Eight (67%) were completely excised during the initial endoscopy with 4 requiring re-excision. Only 2 patients developed recurrence, after 2.5 and 10 years and this necessitated a pancreaticoduodenectomy. Five patients had complications (2 for bleeding and 3 for post-ERCP pancreatitis), with zero deaths. Conclusions: Unlike duodenal carcinoids, ampullary NET are rare. Pancreaticoduodenectomy can be offered to fit patients except for gangliocytic paragangliomas that do not require an aggressive operation. However, for those that refuse surgery or are poor candidates, endoscopic ampullectomy can be an option with acceptable short and long-term outcomes.

Surgical treatment of neuroendocrine tumors in the second portion of the duodenum: a single center experience and systematic review of the literature.

The treatment of choice for duodenal neuroendocrine tumors (NETs) ranges from endoscopic resection and local excision to pancreaticoduodenectomy. The aim of this study was to investigate the optimal treatment for this tumor. We retrospectively analyzed the clinicopathological data of 14 patients with NETs in the second portion of the duodenum who underwent surgery in our hospital from 2000 to 2015. The duodenal NETs were classified as either ampullary or non-ampullary. Additionally, a systematic review and pooled analysis was conducted. Among eight patients with ampullary NETs and six patients with non-ampullary NETs, seven and three patients underwent pancreaticoduodenectomy and one and three patients underwent local resection, respectively. The maximum tumor diameter were 11-30mm in ampullary and 10-100mm in non-ampullary NETs, respectively. In patients with ampullary NETs, lymph node metastases were suspected in only three cases preoperatively, but five patients actually had regional nodal metastases. Among patients with non-ampullary NETs, lymph node metastases were suspected in none preoperatively, but three of the four patients who underwent lymph node dissection had regional nodal metastases. According to a pooled analysis of 1245 patients in 88 studies, even small tumors confined to the submucosal layer and G1 tumors-ampullary and non-ampullary-have been associated with lymph node metastases. In patients with non-ampullary NETs and lymph node metastasis, 10-year recurrence-free survival rate was 51% for patients who underwent pancreaticoduodenectomy (n=19) and 53% for patients who underwent partial duodenal resection (n=9), respectively (p=0.960). Lymph node metastases were common in association with both ampullary and non-ampullary NETs, and it was difficult to radiologically diagnose metastases. Additionally, there were no clinicopathological factors that could reliably predict the absence of lymph node metastases preoperatively. Therefore, to maximize the ability to achieve a curative resection, pancreaticoduodenectomy is considered appropriate in well-conditioned patients with NETs in the second portion of the duodenum. However, to further clarify the impact of lymph node dissection on survival after duodenal NET resection, a multi-institutional study with a large number of patients, thorough examination of lymph node metastasis, and a long observation period is warranted.

Ampullary Neuroendocrine Tumor in a Cirrhotic Patient without Neurofibromatosis: Case Report

A 61 year old African American gentleman with cirrhosis secondary to Hepatitis C was referred for evaluation of an ampullary lesion. He presented with intermittent, epigastric abdominal pain with early satiety but no nausea, vomiting, or weight loss, and there was no personal or family history of neurofibromatosis. He underwent an EGD that revealed a 2 cm ampullary lesion, biopsies positive for low-grade NET. Somatostatin receptor scintigraphy as well as serum gastrin and chromogranin levels were normal. The patient underwent EUS which revealed a 2cm well-circumscribed lesion involving the major papilla, confined to mucosal and submucosal layers, with no intraductal extension. Next, using a side-viewing duodenoscope, a papillectomy including en bloc resection of the lesion was accomplished using salinelift snare-cautery from a caudal approach (Figure 1). Stents were placed in both the common bile and pancreatic ducts (Figure 2). Pathology of the mass revealed well-differentiated NET, positive for synaptophysin and chromogranin, Ki-67 index of 1%. Three weeks following the procedure, stents were removed and multiple random biopsies were taken to assess for remnant carcinoid tumor, which were negative. Ampullary neuroendocrine tumors are rare, comprising less than 2% of tumors of the ampulla of Vater. Due the rarity of these tumors, treatment protocols regarding ampullary neuroendocrine tumors are controversial. Endoscopic resection may be undertaken in those with smaller tumors that do not invade the muscularis propria and with less than one centimeter of intraductal extension. In potential candidates, endoscopic ultrasound is used for assessment of tumor stage, including depth of intraductal extension, which may then be followed by ERCP for endoscopic papillectomy and ductal stenting in those with amenable features. Several studies have suggested endoscopic resection of small periampullary NETs has similar outcomes as surgical resection but with significantly less morbidity. Surgical management is usually recommended for larger ampullary NETs and those with other features unfavorable for endoscopic resection. In those with amenable features or at increased risk for adverse events from surgery, such as the patient described above, endoscopic papillectomy represents a viable treatment modality for ampullary NETs.Figure 1Figure 2Figure 3

Is there an Optimal Surgical Approach to Neuroendocrine Tumors of the Ampulla? A Single Institution Experience over 15 Years

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare neoplasms accounting for a small fraction of gastroenteropancreatic NETs. The optimal surgical approach remains controversial. This study aimed to define the optimal approach in patients with ampullary NETs. Patients who underwent resection of ampullary NETs from 2000 to 2014 were analyzed. Fourteen patients with well-differentiated, nonfunctional NETs were identified. The mean age was 60 ± 15 years, and nine (64%) were male. The mean tumor size was 1.6 ± 0.9 cm and the majority (61%) had an advanced tumor-node-metastasis stage. Eight (57%) patients underwent pancreaticoduodenectomy (PD) and six (43%) underwent transduodenal ampullectomy (TA). Although the mean tumor size was similar (1.7 vs 1.5 cm), the majority (75 vs 20%) of PD patients demonstrated a trend toward more aggressive tumors, characterized by advance T stage in 25 vs 0 per cent, lymph node positivity in 88 vs 17 per cent, and elevated proliferative index (Ki-67) in 25 vs 0 per cent. Complete resection (R0) was achieved in all PD patients versus 75 per cent in TA patients. There was no difference in major complication rate (50 vs 33%). In the TA group, one (17%) patient recurred and two (33%) patients died, whereas only one (13%) patient died in the PD group and no patients recurred. In conclusion, ampullary tumors can be aggressive tumors characterized by high regional lymph node involvement. A transduodenal approach may provide an inadequate oncological resection and thus has the potential to understage ampullary NETs. In the era of increasing therapeutic options for gastroenteropancreatic NETs, accurate staging is crucial and appropriate oncologic resection via PD for ampullary NETs should be considered.

A radiologically atypical case of an ampullary neuroendocrine tumor

Ampullary neuroendocrine tumors (ANETs) are rare tumors which show characteristic CT features. We present a case of a 42-year-old female, in which the CT features of an ampullary tumor were atypical for a neuroendocrine tumor but was confirmed on histopathology and immunohistochemistry as an NET. The uniqueness of our case was that the lesion showed mild enhancement in the arterial phase which was persistent in the venous phase with wash out in the delayed phase

Mixed periampullary adenocarcinoma and somatostatinoma with small bowel gastrointestinal stromal tumour in neurofibromatosis type 1.

Gastrointestinal (GI) involvement is present in about one quarter of cases of neurofibromatosis type 1 (NF1). Adenocarcinomas have been reported in several organs. Gastrointestinal stromal tumors are the most common GI lesion seen in NFI. GISTs in combination with ampullary neuroendocrine tumors in NF-1 have been reported rarely. We present the case of a 44-year-old man who presented with a history of obstructive jaundice and weight loss. Investigations revealed a pancreatic tumor associated with a common bile duct (CBD) stricture. At operation, an ampullary adenocarcinoma that infiltrated into the head of pancreas with an adjacent somatostatinoma was found. In addition, a small bowel GIST was present. Mixed periampullary adenocarcinoma and somatostatinoma in a patient with NF1 has only been previously reported once. The current case highlights the spectrum of associated tumor types which can be seen in association with NF1. Patients with NF1 who present with jaundice and weight loss should be investigated in the usual manner with increased suspicion for duodenal and ampullary tumors.

Clinical Outcomes for Neuroendocrine Tumors of the Duodenum and Ampulla of Vater:A Population-Based Study

BackgroundPrevious case series report that neuroendocrine tumors (NETs) of the ampulla of Vater have worse overall survival (OS) than NETs in the duodenum. We aimed to compare the OS of patients with ampullary NETs to patients with duodenal NETs. MethodsThis retrospective comparative cohort study used the Surveillance, Epidemiology, and End Results (SEER) registry from 1988 to 2009. OS was evaluated using Kaplan–Meier estimates and Cox proportional hazard regression. ResultsAmpullary NETs (n = 120) were larger (median size 18 vs. 10 mm, p < 0.001), higher grade (poorly and undifferentiated tumor 42 % vs. 12 %, p < 0.001), higher SEER historic stage (distant metastasis 16 % vs. 7 %, p < 0.001), and more often resected (78 % vs. 60 %, p < 0.001) than duodenal NETs (n = 1,360). Median OS was significantly worse for patients with ampullary NETs than with duodenal NETs (98 vs. 143 months, p = 0.037). Local resection was performed for 50.5 % of the resected ampullary NETs and resulted in similar OS compared to locally resected duodenal NETs (HR 1.37, 95 % CI 0.76–2.48, p = 0.291). ConclusionsWhile ampullary NETs are more advanced at presentation and have worse OS than duodenal NETs, long-term survival is possible with proximal small bowel NETs. For locally resected NETs, OS is similar between ampullary and duodenal NETs.

Inhibin-expressing clear cell neuroendocrine tumor of the ampulla: an unusual presentation of von Hippel–Lindau disease

von Hippel-Lindau (VHL) disease is a hereditary autosomal dominant disorder associated with deletions or mutations in the VHL tumor suppressor gene. Characteristically, up to 60% of neuroendocrine tumors (NETs) associated with VHL disease display a spectrum of clear cell morphology including multivacuolated lipid-rich cell change. Unlike neurofibromatosis type 1 and multiple endocrine neoplasia type 1 syndromes, ampullary NETs have not been described in association with VHL disease. In this report, we discuss the features of an incidental ampullary clear cell NET occurring in a patient with pancreatic VHL disease including multiple pancreatic NETs. The ampullary lesion consisted of epithelial cells resembling lipoblasts or signet ring cells. In our case, all NETs showing clear cell change were positive for inhibin. While the underlying mechanism of this finding is largely unknown, it is of note that positivity for inhibin has not been observed in clear cell NETs associated with multiple endocrine neoplasia type 1 syndrome. Our case proves that NETs can develop in the ampullary region in patients with VHL; clear cell change can occur in these lesions and can mimic signet ring cell carcinoma. This issue is of clinical significance especially in small biopsy samples; thus, positivity for keratin alone should not be taken as evidence of an adenocarcinoma. Moreover, demonstration of inhibin expression in a NET with clear cell change along with other clinical stigmata should alert the diagnostician to the possibility of VHL disease. However, further larger series examining inhibin expression in both syndrome-related and sporadic clear cell NETs are needed to confirm our findings.

Su1666 Clinical Outcomes for Neuroendocrine Tumors of the Duodenum and Ampulla of Vater: A Population-Based Study

Background Previous case series report that neuroendocrine tumors (NETs) of the ampulla of Vater have worse overall survival (OS) than NETs in the duodenum. We aimed to compare the OS of patients with ampullary NETs to patients with duodenal NETs.