Case Of Pancreatic Neuroendocrine Tumor Research Articles

A comparative study of INSM1 (clone MRQ70) immunoreactivity on CytoLyt® pretreated cytology and resection specimens of pancreatic neuroendocrine tumors.

Insulinoma-associated protein 1 (INSM1) is a newly characterized sensitive and specific immunohistochemical marker for neuroendocrine (NE) tumors. Whereas more traditional NE markers, such as chromogranin A and synaptophysin, are cytoplasmic, INSM1 is uniquely nuclear and thus could serve as a useful addition to NE tumor workup. While application of immunohistochemical studies to cytology specimens is becoming increasingly relevant, knowledge of the effects of the certain fixatives as well as the pattern and intensity of immunoexpression are important considerations. Sixteen cases of pancreatic neuroendocrine tumor (PanNET) diagnosed between 2015 and 2021 underwent both fine-needle aspiration, which was subsequently prepared in CytoLyt®-fixed cytology cell block (CCB), and surgical resection, in which specimens were prepared into formalin-fixed paraffin embedded blocks (FFPE). For all samples, INSM1 immunoreactivity was classified according to staining intensity and extent, then compared between CCBs and matched FFPEs. All 16 FFPE specimens demonstrated strong and diffuse INSM1 immunoreactivity, while only 10/16 (62.5%) CCBs were positive. Of those 10, only 2/10 (20%) demonstrated strong and diffuse reactivity. The choice of fixative has a demonstrable effect on the immunoreactivity of INSM1 in PanNET. Even though the sensitivity is lower in CytoLyt®-fixed cell block specimens, the addition of INSM1 is useful, especially in challenging cases that may be negative for one or more of the traditional NE markers.

Endoscopic loco-regional treatment in controlling pancreatic neuroendocrine tumors (PNETs) behavior: a case series and literature review.

Pancreatic neuroendocrine tumors (PNETs) are considered rare pancreatic neoplasms, and it is a challenging disease entity due to its indolent behavior and is difficult to manage. Diagnostic challenge is usually found in the imaging-based approach, such as transabdominal ultrasound, abdominal CT scan, and abdominal MRI. Surgery is still the main key player in controlling the disease. The main problems in clinical practice are the early detection of small PNETs lesion and non-functional PNET (NF-PNET) cases. Most cases usually come with large tumor size or metastatic disease. Endoscopic ultrasound (EUS) has been well-known as the most sensitive tool for early detection of pancreatic malignancy. It has now also been developed for managing pancreatic cancer, such as tumor ablation therapy. We presented four variety of PNETs cases (one patient with non-functioning PNETs and three patients with functioning PNETs) who have been successfully treated with EUS-guided radiofrequency ablation (RFA) with good control of tumor growth during follow-up. One patient with a large-size insulinoma could have the tumor controlled gradually after several EUS-RFA sessions. No adverse events or major complications were observed during and after the EUS-RFA procedure. EUS has been shown as a promising tool not only for more accurate diagnosis but also for tumor growth control. However, it would need further comparison studies between EUS and surgical approaches to make a better treatment strategy.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

Study on the application value of fluorescent laparoscopy in pancreatic tumor surgery.

Fluorescent laparoscopy is rarely used in pancreatic surgery. The aim of this study was to investigate the value of fluorescent laparoscopy in pancreatic tumor surgery. A total of 19 patients with pancreatic tumors who were treated in the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to August 2022 were selected. Fluorescent laparoscopy was used intraoperatively, and the imaging characteristics of different tumors were recorded and analyzed. Among the 19 participants, postoperative pathology confirmed 12 cases of pancreatic cancer (8 cases of moderately differentiated adenocarcinoma, 3 cases of moderately-poorly differentiated adenocarcinoma, and 1 case of acinar cell carcinoma), 4 cases of pancreatic cystic tumors (1 case of microcystic serous cystadenoma, 1 case of serous cystadenoma, 1 case of solid pseudopapillary tumor, and 1 case of solid-cystic pseudopapillary tumor), 1 case of pancreatic neuroendocrine tumor (G1 stage), and 2 cases of inflammatory lesions. There were 8 cases of pancreaticoduodenectomy, 6 cases of distal pancreatectomy, 3 cases of middle pancreatectomy, 1 case of local pancreatectomy, and 1 case of duodenum-preserving pancreatic head resection. One minute after intravenous injection of indocyanine green (ICG), 10 of the 12 patients with pancreatic cancer showed tumor peritumor imaging; 2 cases of pancreatic serous cystic tumors did not show imaging; 2 cases of solid pseudopapillary tumors had tumor body imaging; 1 case of neuroendocrine tumor had tumor body imaging, with complete fluorescence imaging after specimen dissection; there were 2 cases pathologically confirmed as inflammatory lesions, 1 case with tumor body imaging, and 1 case with capsule imaging. By reasonably controlling the administration time and dose of ICG during surgery, some pancreatic tumors can be fluorescently imaged, which is beneficial for intraoperative tumor localization and margin determination.

Association of guideline adherence in diagnosis and treatment of pancreatic neuroendocrine tumors with survival.

e16241 Background: Clinical guidelines and their adherence are important instruments to ensure quality in diagnosis and treatment, especially when treating rare diseases like pancreatic neuroendocrine tumors (PanNET). However, data on guideline adherence and its impact on outcome in PanNET is limited. Methods: Cases of PanNET according to 2017 WHO definition at our university hospital between 2010 and 2019 were retrospectively identified. Adherence to ENETS guideline 2007/2012 and the German S2k guideline was evaluated among four categories (diagnostics: chromogranin A (CgA) testing, somatostatin receptor imaging, discussion in an interdisciplinary tumor board; pathology: reporting of grading, Ki67 and synaptophysin expression; surgical treatment; systemic treatment including aftercare). Guideline adherence within these categories was valued with one point per fulfilled criterion and a final score between 0-8 points was calculated. Data was analyzed using Student’s t-test, Chi-square test and Spearman’s correlation coefficient test. Results were considered significant at α = 0.05. Results: Overall, 115 patients (47% female) with a diagnosis of PanNET were identified. Mean age was 61 (±13.5) years. Mean overall survival (OS) was 45 months, mean recurrence free survival (RFS) was 47 months. During the study period 21 patients (18%) had died, 6 patients (5%) were lost-to-follow-up and 11 patients (10%) had a recurrent disease after initially curative resection. 24 patients (21%) presented with metastatic disease upon diagnosis. Guideline adherence concerning pathology reports (97%) as well as systemic (91%) and surgical treatment (75%) was high, while complete adherence in diagnostic modalities was low (5%). However, the latter was mainly driven by lack of CgA testing (31%), and somatostatin receptor imaging (11%) not being performed on initial diagnosis, but in most cases during follow-up. Subsequently, complete guideline adherence (8/8) across all categories was rare (3%). However, a higher overall score was associated with survival (p = 0.032, V = 0.321). Long term survivors had a higher mean overall adherence score (5.6 vs. 6.1; p = 0.05). In addition, the composite score of surgical and systemic therapy was significantly correlated with RFS (ρ = 0.254, p = 0.016). Conclusions: The quality in diagnosis and treatment of PanNET in our cohort was high. These are the first data to demonstrate a positive impact of guideline adherence on survival and RFS in PanNET.

Improving fine needle aspiration to predict the tumor biological aggressiveness in pancreatic neuroendocrine tumors using Ki-67 proliferation index, phosphorylated histone H3 (PHH3), and BCL-2

IntroductionSurgery is the only known cure for sporadic pancreatic neuroendocrine tumors (PNETs). Therefore, the prediction of the PNETs biological aggressiveness evaluated on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has a significant impact on clinical management. The proliferation rate of Ki-67 in PNETs can help to predict the biological aggressiveness of the tumor. In addition, there is a relatively new proliferation marker called phosphorylated histone H3 (PHH3) that can identify and quantify dividing cells in tissue samples, which is a marker highly specific to mitotic figures. Other markers such as BCL-2 also contribute to tumorigenesis and may be involved in the differentiation of neuroendocrine cells. Materials and methodsA retrospective observational study was performed on patients undergoing surveillance for PNETs from January 2010 to May 2021. Data collection included the patients' age, sex, tumor location, tumor size in the surgical specimen, and tumor grade in FNA. The 2019 World Health Organization (WHO) classification guideline was followed to diagnose PNETs, including grade and stage. Immunohistochemical stainings for Ki-67, PHH3 and BCL-2 in PNETs were performed. ResultsAfter excluding cell blocks containing fewer than 100 tumor cells, 44 patients with EUS-FNA and surgical resection specimens were included in this study. There were 19 cases of G1 PNETs, 20 cases of G2 PNETs, and 5 cases of G3 PNETs. The grade assigned based on the Ki-67 index was higher and more sensitive than that based on the mitotic count using H&E slides in some cases of G2 and G3 PNETs. However, there was no significant difference between the mitotic count using PHH3-positive tumor cells and the Ki-67 index to grade PNETs.All grade 1 tumors (19 cases) on surgical resection specimens were correctly graded on FNA (100 % concordance rate). Within the 20 G2 PNETs, 15 cases of grade 2 on surgical resection specimens were graded correctly on FNA based on the Ki-67 index only. Five cases of grade 2 PNETs on surgical resection specimens were graded as grade 1 on FNA when using only the Ki-67 index. Three of five grade 3 tumors on surgical resection specimens were graded as grade 2 on FNA based on the Ki-67 index only. Using only FNA Ki-67 to predict PNET tumor grade, the concordance (accuracy) rate was 81.8 % in total. However, all these eight cases (5 cases of G2 PNETs and 3 cases of G3 PNETs) were graded correctly by using the Ki-67 index plus mitotic rate (using PHH3 IHC stains).Four of 18 (22.2 %) patients with PNETs were positive for BCL-2 stain. In these 4 cases positive for BCL-2 stains, 3 cases were G2 PNETs and one case was G3 PNETs. ConclusionGrade and the proliferative rate in EUS-FNA can be used to predict the tumor grade in surgical resection specimens. However, when using only FNA Ki-67 to predict PNET tumor grade, about 18 % of cases were downgraded by one level. To solve the problem, immunohistochemical staining for BCL-2 and especially PHH3 would be helpful. Our results demonstrated that the mitotic count using PHH3 IHC stains not only improved the accuracy and precision of PNET grading in the surgical resection specimens, but also could reliably be used in routine scoring of mitotic figures of FNA specimens.

A case of pancreatic neuroendocrine tumor with amyloid deposition (insulinoma) predicted by rapid on-site evaluation of pancreatic endoscopic ultrasound-guided fine-needle aspiration specimen

A case of pancreatic neuroendocrine tumor with amyloid deposition (insulinoma) predicted by rapid on-site evaluation of pancreatic endoscopic ultrasound-guided fine-needle aspiration specimen

The sun beside the pancreatic neck: The lymph node gastrinoma (with video).

The sun beside the pancreatic neck: The lymph node gastrinoma (with video).

MK2 Promotes the Development and Progression of Pancreatic Neuroendocrine Tumors Mediated by Macrophages and Metabolomic Factors.

Cases of pancreatic neuroendocrine tumors (PNETs) are growing in number, and new treatment options are needed in order to improve patient outcomes. The mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a crucial regulator of cytokine/chemokine production. The significance of MK2 expression and signaling pathway mediated by MK2 in PNETs has not been investigated. To characterize the impact of MK2 on PNET growth, we used the RipTag2 transgenic murine model of PNETs, and we developed a primary PNET cell line for both in vitro and in vivo studies. In the transgenic murine model of PNETs, we found that MK2 inhibition improves survival of mice and prevents PNET progression. MK2 blockade abolished cytokine/chemokine production, which was related to macrophage function. A role for MK2 in the regulation of metabolic factor secretion in PNETs was identified, making this the first study to identify a potential role for the MK2 pathway in regulation of tumor metabolism. Moreover, using an in vitro approach and allograft model of PNETs, we were able to show that macrophages with MK2 depletion exhibit increased cytotoxicity against PNET cells and substantially decreased production of pro-inflammatory cytokines and chemokines, as well as metabolic factors. Taken together, our work identifies MK2 as a potent driver of immune response and metabolic effectors in PNETs, suggesting it is a potential therapeutic target for patients with PNETs.

A case of pancreatic neuroendocrine tumor with cystic degeneration

A case of pancreatic neuroendocrine tumor with cystic degeneration

Genomic correlates of response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine tumors.

4124 Background: Despite the frequent use of capecitabine and temozolomide (CAPTEM) to treat metastatic, well-differentiated pancreatic neuroendocrine tumors (PNETs), no reliable genomic predictors of response currently exist. PNETs commonly harbor mutations in MEN1, ATRX, DAXX, and the PI3K/AKT/mTOR pathway. We sought to determine whether the mutational status of these genes correlates with response to CAPTEM. Methods: A retrospective cohort of PNET cases seen at Cedars-Sinai Medical Center or from Perthera’s Real-World Evidence Database included 23 patients who were treated with CAPTEM in 1st or 2nd line and had targeted next-generation sequencing (NGS) of their tumors available. Genomic alterations were correlated with progression-free survival (PFS) using multivariate Cox regression analysis. Results: We analyzed 23 PNET patients, 4 (17.4%) of whom had documented functional tumors. We identified MEN1 mutations as positively associated with CAPTEM response, but this effect was less pronounced for the subset with co-occurring DAXX mutations, which are commonly found alongside MEN1 alterations. With and without accounting for line of therapy, we found that PFS on CAPTEM was significantly longer in MEN1-mutated, DAXX-wildtype tumors compared to other mutation profiles ( P &lt; 0.01, see Table). ATRX (67%) and PTEN (33%) alterations were also enriched in the MEN1-mutated/ DAXX-wildtype subset; however, other PI3K/AKT/mTOR alterations were common across all MEN1-mutated cases. Conclusions: We describe a novel genomic signature ( MEN1 mut/ DAXX wt) that correlates with PNET response to CAPTEM therapy and is exploratory in nature. Prospective validation of these associations is warranted while taking into account other therapies, histopathologic factors, and other genomic correlates. [Table: see text]

A256 SURVEILLANCE OF SMALL, NON-FUNCTIONING, ASYMPTOMATIC PANCREATIC NEUROENDOCRINE TUMORS: THE BRITISH COLUMBIA EXPERIENCE

Abstract Background Expert consensus surrounding surveillance for small, non-functioning, asymptomatic pancreatic neuroendocrine tumors (PNETs) remains conflicting. Recent observational studies have shown that surveillance is a safe strategy while large database studies show superior overall survival with surgical resection. Aims To describe the growth of small (&amp;lt;2cm), non-functioning, asymptomatic PNETs undergoing surveillance at a tertiary hospital in British Columbia. Methods We conducted a retrospective case series of patients with biopsy-proven, non-functioning, asymptomatic PNETs which were &amp;lt;2cm by RECIST criteria at diagnosis, who were followed through active surveillance at Vancouver General Hospital, British Columbia from February 1, 2011-February 1, 2021. Patients were included if serial imaging, whether by endoscopic ultrasound or cross-sectional imaging, was available for a minimum of 24 months. Results Of the 57 patients with pathology-proven PNETs that were identified, 14 cases were included after excluding those with resection within 1 year (n=17), lost to follow up (n=13), metastatic disease (n=6), size greater than 2cm at diagnosis (n=4), and with concurrent cancer (n=3). Included patients were predominantly female (n=10, 71%), Caucasian (n=8, 57%), and had a mean Charlson comorbidity index of 3.14. Mean PNET size at diagnosis was 12mm with standard deviation of 4.26mm. Tumors were located in the pancreatic head (n=4, 29%), body (n=6, 42%), and tail (n=4, 29%). Of 8 patients who had Ki67 stains, all were &amp;lt;3%, and of 11 patients with mitotic index, all had &amp;lt;2 mitotic figures. As such, of the 8 patients with available WHO grading, all were grade 1. The average follow-up was 49.6 months with an average tumor growth of 0.82mm per year. When grouping these tumors by growth, 9 (62%) tumors exhibited no growth, 2 tumors grew &amp;lt;1mm per year, 2 tumors grew 1-1.5mm per year, and 1 tumor grew 7.7mm per year. Two cases (14%) of PNETs underwent surgical resection due to size surpassing 2 cm. No patients undergoing surveillance developed metastatic disease. Conclusions To our knowledge, we have performed the first Canadian series of small, low-grade PNETS and demonstrated that active surveillance is a safe strategy with most tumors exhibiting no growth of several years. Of the subset of PNETs which demonstrate progression, the preceding surveillance strategy did not disadvantage patients in terms of progression to metastases and allowed for delay of potentially morbid surgery. Further research with prospective studies and larger samples should be conducted. Funding Agencies CAG

A Case of Improvement of Insulinoma Symptoms in Pregnancy

Background: Insulinomas are rare tumors with an incidence of approximately 4 cases per million person per year. Only 39 cases of pancreatic neuroendocrine tumors have been reported in pregnancy. We report a case of pregnancy protecting the mother from manifesting the symptoms of insulinoma. Clinical Case: This case describes a 25-year old female who initially noticed symptoms of generalized weakness and oral tingling sensation in Fall 2018. She became pregnant in March 2019. She noticed an immediate reduction of the intensity of her symptoms during pregnancy. Her pregnancy was uneventful, and she delivered a healthy newborn in November 2019. Two months postpartum, she had worsening symptoms including syncopal episodes, confusion, difficulty ambulating and visual changes that improved with PO intake specifically carbohydrate intake. She was evaluated in March 2020 and labs showed the following: venous glucose 32 mg/dL, C-peptide 1.7 nmol/L, BOHB 0.4 mmol/L, Insulin 6.1 microU/ml, Proinsulin 25.8 pmol/L, IGF-2 354 ng/mL, negative insulin antibodies and negative oral hypoglycemic agent screen. TSH was unremarkable and AM cortisol was 16.1 mcg/dL. She was started on diazoxide twice a day. She underwent MRI of abdomen, which was negative followed by an EUS which was also negative. She had run out of her diazoxide and became severely symptomatic resulting in an ER visit where she was found to be hypoglycemic. Further evaluation was done with a Triple Phase spiral CT which showed a 1 cm arterial enhancing focal lesion within the pancreatic neck compatible with insulinoma. This was further evaluated with EUS FNA which confirmed the diagnosis of insulinoma on pathology. Her chromogranin A was 46.5 ng/mL. She is scheduled for surgical removal of the lesion. Conclusion: Pregnancy leads to an increased insulin resistance through hormonal changes with increased expression of placental growth hormone, human placental lactogen and the placental variant of corticotrophin‐releasing hormone (via ACTH and cortisol production), TNF-alpha and leptin. These changes that increase the insulin resistance act as a protective mechanism against the detrimental effects of an insulinoma. Pregnancy most likely also delayed the diagnosis of the insulinoma in this patient. Further research is warranted to evaluate the effects of an insulinoma on the mother and fetus.

Parenchyma-sparing Resection in a Non-functioning Neuroendocrine Tumor of the Pancreatic Neck

Purpose: The aim is to present a case of pancreatic neuroendocrine tumor treated surgically by parenchymal sparing resection, central pancreatectomy. Method: 53-year-old woman with distended abdomen and intense epigastric pain of 3 days evolution and one year of abdominal discomfort. CT: pancreatic neck tumor. CEA, CA19.9 and negative hormones. Ultrasound-guided FNA: suspected G1 neuroendocrine tumor (Ki67 1% and synaptophysin +). Octreoscan negative for metastasis. Surgical treatment: central pancreatectomy, closure of the proximal pancreatic remnant and pancreatic-gastric anastomosis of the caudal remnant. AP: neuroendocrine tumor of the pancreatic neck G2 (T3N0M0), Ki67 15%, synaptophysin + and CgA +. Results and conclusions: Parenchyma-sparing resections (enucleation and central pancreatectomy) always aim to remove the tumor while preserving the maximum pancreatic tissue. Enucleation is indicated in non-functioning tumors, TNM stages l-ll of ENETS, <2cm, and with a safety margin between the tumor and the main pancreatic duct of 2-3mm. Some authors advocate parenchymal-sparing resections in tumors between 2-4cm, without evident lymph node disease. (In our case, a 3.5x2.5x2cm tumor in the pancreatic neck, with a distance <2-3mm to the pancreatic duct and no lymph node involvement). Lymphadenectomy should be performed based on the degree of tumor differentiation obtained by preoperative FNA, being indicated for G2 tumors, a group that includes tumors with a very wide range of Ki67 with uncertain significance. These resections are associated with a lower rate of de novo diabetes and better exocrine pancreatic function. However, the rate of postoperative fistulas increase, with more postoperative morbidity and risk of reoperations.

A Case of Pancreatic Neuroendocrine Tumor with Cystic Degeneration

A Case of Pancreatic Neuroendocrine Tumor with Cystic Degeneration

S3320 A Rare Case of Metastatic Pancreatic Neuroendocrine Tumor (PNET) in a Young Man

INTRODUCTION: Pancreatic cancers are very aggressive cancers with high metastasizing potential. Pancreatic neuroendocrine tumors (PNETs) are rare cancers that account for 1-2% of pancreatic tumors. We present an unusual case of metastatic PNET occurring in a 32-year-old man. CASE DESCRIPTION/METHODS: A 32-year-old male without past medical history presented with worsening diffuse abdominal pain and nausea for 3 weeks. He also reported clay-colored stool, intermittent diarrhea, and stabbing abdominal pain. Labs showed total bilirubin 3.1 (0.3-1.2), direct bilirubin 2.2 (0-0.3), alk phos 173 (50-136), AST 124 (15-40), ALT 200 (4-47), and lipase 707 (59-393). Hepatomegaly was noted on the physical exam. Abdominal US demonstrated hepatomegaly with multiple isoechoic hepatic masses. CT A and P showed pancreatic body neoplasm with diffuse hepatic metastasis. Ca-19 and CEA tumor markers were within normal limits. Endoscopic US revealed an irregular pancreatic body mass measuring 30 mm × 25 mm. FNA showed high-grade neuroendocrine carcinoma with small cell features. FNA malignant cells were positive for CD56, Claudin4, pankeratin, with high proliferative activity (Ki-67 proliferation index is 60%). The patient was diagnosed with metastatic Stage 4 pancreatic cancer. The patient was discharged and later admitted to a different hospital with intractable abdominal pain and worsening jaundice. MRI of the pancreas showed 3.6 cm × 2.9 cm primary pancreatic neoplasm and innumerable hepatic metastasis replacing x >50% of the liver parenchyma. US-guided FNA of hepatic metastasis revealed small cell carcinoma with the Ki67 proliferation index greater than 90%. The tumor was positive for pancytokeratin (AE1/AE3), epithelial membrane antigen, synaptophysin, and CD56. Few tumor cells were positive for GI markers CDX2 and SATB2. Unfortunately, the patient was not a candidate for any intervention, and he was discharged to continue palliative chemotherapy at home. DISCUSSION: PNETs are malignant tumors with an insidious presentation. PNETs have a varied clinical manifestation, including abdominal pain, nausea, jaundice, and anorexia. Unfortunately, as demonstrated in this patient, pancreatic cancers often present with non-specific early symptoms and are identified at advanced stages with multiple metastases. Treating metastatic pancreatic cancer, especially in a young man, is challenging as the mainstay of treatment remains palliative.Figure 1.: PNET with diffuse hepatic metastasis on CT abdomen and pelvis.Figure 2.: PNET with diffuse hepatic metastasis on CT abdomen and pelvis.

Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report

BackgroundPancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.Case presentationA 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.ConclusionsDifferential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.

Abstract D113: Socioeconomic disparities underlie outcomes in patients with pancreatic neuroendocrine tumors

Abstract Background Disparities are known to underlie outcomes in pancreatic ductal adenocarcinoma (PDAC). Pancreatic neuroendocrine tumors (PNET) represent a rare yet deadly form of pancreatic cancer. Health disparities have not been well described in this patient population. We hypothesize that given the significant health disparities in PDAC, cancer health disparities exist in patients with PNETs. Methods Patients treated for PNETs were identified in a National Cancer Database (NCDB) Patient User File for the years 2004-2015. Kaplan-Meier analysis was performed to assess survival. Cox proportional hazards models were used to assess the effect of clinical and socioeconomic factors on survival. Results Review of the NCDB found 19,752 reported cases of PNETs. Of those, 15,589 (78.9%) were non-Hispanic white (NHW), 2,462 (12.5%) were black (B), and 1,710 (8.6%) were Hispanic, white (H). On univariate analysis, greater age, male sex, higher Charlson comorbidity score, higher disease stage, lack of insurance, decreased median household income in area of residence, and no surgery were associated with worse survival (p&amp;lt; 0.05). While not statistically significant and unlike pancreatic adenocarcinoma, black patients had greater median survival (89.6 months; 95% CI 77.9-101.196) compared to NHW (76.4 months; 95% CI 72.9-79.8) and H (80.1 months; 95%CI 70.7-89.5) patients. On multivariate analysis, the same factors from the univariate analysis were associated with worsened survival (p&amp;lt; 0.05). Sub-analyses of patients who received surgery and those who did not again showed no significant difference in survival based on race. Conclusion While insurance status, median income in area of residence, and sex were associated with clinical outcomes in PNETs, race was not a contributing factor. This is in contrast to literature in PDAC which has demonstrated that black patients have worse survival. The reasons for this difference are unclear, but may biologically driven. It is important to understand disparities from different types of pancreatic tumors. Further work to understand biologic contributions to health inequities are needed. Citation Format: Patrick W Underwood, Andrea N Riner, Michael U Maduka, Sushanth Reddy, J. Bart Rose, Jose G Trevino. Socioeconomic disparities underlie outcomes in patients with pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D113.

The first pancreatic neuroendocrine tumor in Li-Fraumeni syndrome: a case report

BackgroundLi-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome.Case presentationThis is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. When the patient was 41 years old, her seven-year-old daughter was found to have an astrocytoma and a germline TP53 mutation. While undergoing surveillance with 68Gallium-DOTATATE positron emission tomography/computed tomography for her PNET, the patient was found to have a large choroid plexus papilloma in her right temporal lobe. She underwent genetic counseling and testing that identified a germline pathogenic variant in TP53, leading to the diagnosis of Li-Fraumeni syndrome. Her PNET had a hemizygous pathogenic TP53 mutation with loss of the wild-type alternate allele, consistent with loss of heterozygosity and the two-hit hypothesis. She was enrolled in a Li-Fraumeni syndrome protocol and continues surveillance screening with our service.ConclusionsThis is the first PNET reported in association with Li-Fraumeni syndrome. Pancreatic cancer risk is elevated in this syndrome, and our case highlights the need for vigilance in screening for pancreatic neoplasms in these patients.

Insulinoma-associated protein 1 (INSM1) is a robust marker for identifying and grading pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumor (PNET) is a diagnostic challenge with limited samples in not only identification but grading. Prior studies have shown insulinoma-associated protein 1 (INSM1) to be a robust marker in identifying PNETs from other solid pancreatic tumors on resection specimens. In this study, we investigated the utility of INSM1 not only for identifying PNETs but also for grading in cell blocks (CBs) and surgical resections (SRs). A search for PNET cases between 2000 and 2019 identified 55 samples (26 CBs and 29 SRs) that were further separated into high (2 CBs, 3 SRs), intermediate (4 CBs, 7 SRs), and low (20 CBs, 19 SRs) grades based on their final pathology report and Ki-67 level. Immunohistochemical (IHC) staining for INSM1 (C-8, Santa Cruz Biotechnology [1:100]) was performed and quantified using an H score of 0 to 300. Non-PNET solid pancreatic tumors were compared and included acinar cell carcinoma, solid pseudopapillary neoplasm, and ductal adenocarcinoma. All 55 cases of PNET demonstrated nuclear INSM1 staining. The average H scores for INSM1 staining of PNET were 254 and 252 in CB and SR, respectively. The H scores decreased with increasing tumor grade, with low-grade (G1), intermediate-grade (G2), and high-grade (G3) tumors showing average INSM1 H scores of 229 and 253, 266 and 253, and 30 and 33 in both CB and SR, respectively. IHC with INSM1 plays a role in identifying and potentially grading PNETs.