Well-differentiated Endocrine Tumors Research Articles

Peptide Receptor Radionuclide Therapy.

The concept of using a targeting molecule labeled with a diagnostic radionuclide for using positron emission tomography or single photon emission computed tomography imaging with the potential to demonstrate that tumoricidal radiation can be delivered to tumoral sites by administration of the same or a similar targeting molecule labeled with a therapeutic radionuclide termed "theranostics." Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs (SSAs) is a well-established second/third-line theranostic treatment for somatostatin receptor-positive well-differentiated (neuro-)endocrine neoplasms (NENs). PRRT with 177Lu-DOTATATE was approved by the regulatory authorities in 2017 and 2018 for selected patients with low-grade well-differentiated gastroenteropancreatic (GEP) NENs. It improves progression-free survival as well as quality of life of GEP NEN patients. Favorable symptomatic and biochemical responses using PRRT with 177Lu-DOTATATE have also been reported in patients with functioning metastatic GEP NENs like metastatic insulinomas, Verner Morrison syndromes (VIPomas), glucagonomas, and gastrinomas and patients with carcinoid syndrome. This therapy might also become a valuable therapeutic option for inoperable low-grade bronchopulmonary NENs, inoperable or progressive pheochromocytomas and paragangliomas, and medullary thyroid carcinomas. First-line PRRT with 177Lu-DOTATATE and combinations of this therapy with cytotoxic drugs are currently under investigation. New radiolabeled somatostatin receptor ligands include SSAs coupled with alpha radiation emitting radionuclides and somatostatin receptor antagonists coupled with radionuclides.

Insulinoma masquerading as neurologic disease – Case report and review of the literature

Insulinomas are the most frequent etiology of hypoglycemia in a non-diabetic patient and the most common functional neuroendocrine tumors of the pancreas, with an annual incidence of about 4 cases per million1, 2. The majority of insulinomas are “well-differentiated endocrine tumors” or grade 1 tumors, as defined by World Health Organization3 . Most tumors are benign, solitary and occur sporadically. However, about 10% are associated with multiple endocrine neoplasia type 1 (MEN-1)1,2. Despite the majority being benign tumors, hypoglycemic symptoms caused by the hyperinsulinemia are frequently debilitating4 . Whipple triad (hypoglycemia, symptoms of hypoglycemia – either adrenergic or neuroglycopenic – and relief of these symptoms after administration of glucose) is usually present and should alert to the diagnosis2,5. After the diagnosis is made, locating the tumor can be challenging because most tumors are small4 . Nonetheless, locating the tumor is crucial, once the only definite treatment is surgical excision1,2. The majority of patients reach normalization of glucose levels after surgery. Incomplete resection leads to persistent symptoms and although uncommon in sporadic insulinomas, recurrence can be as high as 20% in patients with MEN-1 syndrome6,7.

A Case of Insulinoma With Provoked Seizures for the Past Fourteen Years: A Case Report

Introduction: Insulinoma is one of the most common neuro-endocrine tumors of the pancreas. Some cases with insulinoma present neuropsychiatric symptoms and are often misdiagnosed as psychosis thus patients may remain symptomatic from one week to as long as several decades before diagnosis. Case Presentation: A 68-year-old male patient, who presented episodic seizures and a normal Electroencephalography (EEG) recording for the past fourteen years, had referred for evaluation of hypoglycemia. His biochemical profile revealed blood glucose of 45mg/dL. His C-peptide and insulin levels were elevated. Endoscopic pancreatic ultrasonography (EUS) revealed two mass lesions in pancreatic head. Pathological evaluation revealed well-differentiated endocrine neoplasm and granulomatous reaction in lymph nodes. After resection of the tumor, his symptoms resolved and he became seizure free. Conclusions: Some cases with insulinoma that present neuropsychiatric symptoms might remain symptomatic for several decades before diagnosis. Therefore, it is important for physicians to be aware of presentations of insulinoma to avoid diagnostic delays.

Abstract 3293: Molecular evidence for a parent of origin effect in pediatric insulinomas

Abstract Insulinomas are well-differentiated pancreatic endocrine tumors that cause abnormal beta cell proliferation and hyperinsulinimic hypoglycemia. With an incidence of 2-4 cases per million per year, insulinomas are rare in adults and even less common in children. Since congenital focal hyperinsulinism, another developmental lesion, is associated with paternal isodisomy for the imprinted 11p15 locus, we sought to characterize the role of this region and of mutations in MEN1 on 11q13 in pediatric insulinoma cases. We identified 13 pediatric insulinoma cases, which is the largest pediatric series reported, and performed immunohistochemical analysis for the maternally expressed tumor suppressor marker p57 located in 11p15. Using blood and tumor DNA, we tested 9 candidate genes associated with congenital hyperinsulinism including ABCC8, KCNJ11 and the MEN1 tumor suppressor. We performed methylation analysis of imprint control regions (ICR) that included the paternally expressed IGF2 (ICR1) and maternally expressed CDKN1C (ICR2) located on 11p15 and genome-wide SNP array analysis with tumor DNA. MEN1 mutations were found in 4 cases and suspected in one (MEN1 group); all 5 tumors stained negative for p57 and were hypermethylated at ICR1 and hypomethylated at ICR2 indicating loss of the maternal allele. SNP arrays confirmed loss of heterozygosity (LOH) of entire chromosome 11 in 4 cases. Four out of the 6 remaining non-MEN1 cases also stained negative for p57; in confirmation, 2 of the 4 cases carried mosaic copy number abnormality of chromosome 11. SNP array data demonstrated extensive genome-wide aneuploidy in MEN1 and non-MEN1 cases; however interstitial changes were not present in any of the cases. Notably, MEN1 cases carried only entire chromosome changes, while non-MEN1 cases carried whole arm changes in addition whole chromosome changes. In conclusion, MEN1 mutations are more common in pediatric insulinomas than in adult insulinoma cases (40% in this study vs. 8% in adults). Compared to adult cases, our pediatric insulinoma cases had smaller sized tumors and a shorter median duration of symptoms, suggesting that these tumors are rapidly growing and that the most common chromosome gains and losses very likely represent early events in insulinoma development. Mechanistically, our data suggest that loss of p57 expression, in conjunction with loss of either MEN1 and/or additional imprinted genes on 11p, play a role in the pathogenesis of most insulinomas. In cases with a germ-line MEN1 mutation, we identified a previously unreported paternal parent-of-origin effect that is unique to pediatric insulinomas but not to other MEN1 endocrine tumors (e.g., prolactinoma, parathyroid adenoma). Since a congenital focal hyperinsulinism has a similar parent of origin effect this suggests a broader role for the imprinted locus, 11p15, in not just the pathogenesis of pediatric insulinomas but also in beta-cell replication. Citation Format: Arupa Ganguly, Tricia Bhatti, Karthik Ganapathy, Laura Conlin, Courtney MacMullen, Susan Becker, Eduardo Ruchelli, Charles Stanley. Molecular evidence for a parent of origin effect in pediatric insulinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3293. doi:10.1158/1538-7445.AM2015-3293

P53, KI-67, CD117 expression in gastrointestinal and pancreatic neuroendocrine tumours and evaluation of their correlation with clinicopathological and prognostic parameters.

Gastrointestinal and pancreatic neuroendocrine tumors (GEPNETs) originate from the cells of the endocrine system. Their molecular genetic mechanism of development and progression is complex and remains largely unknown. The purpose of this study was to review the gastrointestinal and pancreatic neuroendocrine tumors and to evaluate p53, Ki-67 and CD 117 expressions with their clinicopathological correlations. Twenty-one patients were reviewed and classified as having well-differentiated neuroendocrine neoplasm (WDET, Grade I), well-differentiated neuroendocrine carcinoma (WDEC, Grade II) and poorly differentiated neuroendocrine carcinoma (PDEC, Grade III). We performed immunohistochemical tests to characterize the expession of the immunoreactivity for synaptophysin, chromogranin, p53, Ki67 and CD 117. Median age of 21 patients was 43 years. Thirteen (61.9%) patients were male and eight (38.1%) patients were female. Tumors were located in the stomach (38.1%), appendix (38.1%), duodenum (4.8%), ileum (4.8%), colon (9.5%), and pancreas (4.8%). There was a statistically significant difference between well-differentiated endocrine neoplasm (Grade I), and well-differentiated endocrine carcinoma (WDEC, Grade II) and PDEC for Ki-67 >20% (p<0.001) (Pearson chi-square test). There was a statistically significant difference between WDET (Grade I), WDEC (Grade II) and PDEC (Grade III) for p53 positivity (p<0.05) (Pearson chi-square test).

Pancreatic neuroendocrine tumors: an analysis of 88 patients

Objective To analyze the clinicopathological characteristics,diagnosis,treatment outcomes and prognosis of patients with pancreatic neuroendocrine tumors (PanNETs).Methods The clinicopathological characteristcs and prognostic factors of 88 patients who were diagnosed with pancreatic neuroendocrine tumors by postoperative pathology were analyzed retrospectively.The data included age,sex,symptoms,tumor size,pathological grades,TNM staging,treatment and follow up.Results There were 28 males and 60 females.The ratio of male to female was 1 ∶ 2.1,with a mean age of 42 (range 8～75) years.Of the 88 PanNETs,74(84.1％) were nonfunctional tumors.Using the WHO 2000 pathological classification system,there were 35 well differentiated endocrine tumors (WDET),29 well differentiated endocrine carcinomas (WDEC),and 24 poorly differentiated endocrine carcinomas (PDEC).Using the 7th AJCC TNM staging system,23(26.1％),46(52.3％),13(14.8％) and 6 patients (6.8％) were diagnosed to have stage Ⅰ,Ⅱ,Ⅲ and Ⅳ,respectively.The overall 5-year survival rate was 72.0 ％.Univariable analysis revealed tumor size,histopathological grades,TNM staging and radical surgery were associated with prognosis.Multivariate analysis showed histopathological grades,TNM staging and radical surgery were independent risk factors of survival.Conclusions PanNETs are rare pancreatic neoplasms with high heterogeneity and low malignant potential.PanNETs have various clinical manifestations and the preoperative misdiagnosis rate is high.A definitive diagnosis depends on pathological examination.The new TNM and pathological classification systems have good predictive abilities on survival.The majority of patients who received radical surgery or surgical comprehensive therapy have good prognosis. Key words: Pancreatic neoplasms; Diagnosis; Therapy; Prognosis

Duodenal somatostatinoma: a case report and review of the literature

IntroductionAbout 70% of well-differentiated endocrine tumors arise from the gastrointestinal tract. Duodenal well-differentiated endocrine tumors account for only 2.6% of all neuroendocrine tumors. Following the first two case reports of somatostatin-secreting tumors in 1977, fewer than 200 cases of somatostatinoma have been reported. These tumors of the duodenum are usually silent and asymptomatic, but can cause gastrointestinal symptoms. Depending on the localization of the tumor, multiple surgical procedures can be performed, ranging from local resection to pancreaticoduodenectomy.Case presentationHere, we report a case of a submucosal duodenal mass in a 42-year-old Turkish White man presenting with nausea, vomiting, fatigue and abdominal pain. The treatment decision of pancreaticoduodenectomy made preoperatively was later altered to intraoperative removal via local resection with sphincteroplasty.ConclusionTumors of the periampullary region are considered highly malignant, and the Whipple operation is usually the only procedural treatment. In the current case, we decided not to perform pancreaticoduodenectomy but to excise the mass intraoperatively, and consequently avoided unnecessary resection of the pancreas and anastomosis to undilated hepatic and pancreatic ducts. This protective strategy prevented duodenum- and pancreas-related morbidity.

Asymptomatic insulinoma: A case report and autopsy series

AimsWe investigated the prevalence and characterization of asymptomatic pancreatic tumors in response to our experience of asymptomatic insulinoma. MethodsA patient with a moderately low glucose level and pancreatic incidentaloma detected by CT was examined. Pancreas specimens from 423 autopsy cases were also pathologically examined systematically by hematoxylin–eosin staining. ResultsThe examined patient showed no profile characteristic of insulinoma by fasting or loading tests, however, ASVS led to diagnosis of insulin-producing tumor. The tumor was resected with the pancreatic body and tail and revealed to be 10mm in diameter, with 98.5% of the cells positive for insulin. Pathological evaluation confirmed a well-differentiated endocrine pancreatic tumor, which was suggestive of an incidentally detected asymptomatic insulinoma. Microscopic evaluations of pancreatic specimens from 423 autopsy cases revealed pancreatic monotonous lesions in 6 cases (1.42%). In 4 autopsy specimens large enough for immuno-histochemical evaluation, the lesions were positive for glucagon but negative for insulin. ConclusionsAs concerns the present study, retrospective immunohistochemical investigation in autopsy cases revealed the presence of asymptomatic glucagonoma but no asymptomatic insulinoma. Advances in diagnostic imaging, however, might raise the probability of detecting early asymptomatic stages of insulinoma incidentally. ASVS appears to be sensitive even for asymptomatic incidental insulinomas.

Hidden Bowel Mass in a Patient with Iron Deficiency Anemia

Purpose: A 72-year-old woman presented to our clinic because of symptomatic iron deficiency anemia. She denied any recent episode of overt bleeding from anywhere or gastrointestinal symptoms. Subsequently she received 2 units of packed red blood cells as hemoglobin continued dropping to the level of 7.0 g/dL. Colonoscopy was finally performed 6 months later as the patient declined the procedure repeatedly. During the colonoscopy procedure, she was found to have bloody material in the cecum without obvious lesions initially (Figure A). The cecum was then deflated and inflated several occasions. During the process, a moderate size sessile lesion arising from terminal ileum was seen invaginating intermittently into cecum. The lesion displayed several erosions on its surface, which explained the presence of bloody material in the cecum (Figure B). Histopathology showed well-differentiated endocrine neoplasm (carcinoid) with mucosal ulcer and granulation tissue reaction. Carcinoid tumors of terminal ileum or ileocecal valve were usually diagnosed by radiological imaging, laparotomy and ileal intubation during colonoscopy. Ileal intubation during colonoscopy has been advocated to be performed to all instances of unexplained lower gastrointestinal bleeding. Our case is the first, to our knowledge, of a moderate size carcinoid tumor of terminal ileum with intermittent appearance to cecum. Ileal intubation as part of colonoscopy is a topic of great debate and a study has demonstrated that performing routine ileal intubation in patients with anemia has little diagnostic value. However, this case highlights the benefit of ileal intubation when evaluating patients with iron deficiency anemia, especially in the presence of bloody material in the cecum.Figure AFigure B

Cap-assisted EMR of large, sporadic, nonampullary duodenal polyps

EMR is an effective alternative to surgery for the removal of nonampullary duodenal polyps (NADPs). Cap-assisted EMR (EMR-C) has been rarely performed in the duodenum because of the risk of perforation. To evaluate the safety and effectiveness of EMR-C for the removal of large (≥ 15 mm) NADPs. Retrospective study. Tertiary-care referral center. Between 2000 and 2010, 26 consecutive patients with sporadic NADPs underwent EMR-C. EMR with the cap technique. Complete eradication of polyps, complications, and recurrence. A total of 14 sessile polyps (53.8%), 7 lateral spreading type nongranular tumors (26.9%), and 5 lateral spreading type granular tumors (19.2%) were treated. The median size of lesions was 15 mm. Five lesions involved one-half of the luminal circumference. Post-EMR histologic assessment showed low-grade dysplasia in 5 patients (19.2%) and high-grade dysplasia in 18 patients (69.2%). Three patients (11.5%) had well-differentiated endocrine tumors. Complete eradication was obtained in 25 of 26 (96%) patients. No perforations occurred. Three cases of intraprocedural bleeding were managed endoscopically. Median follow-up was 6 years (range 1-10 years). Residual adenomatous tissue was observed in 3 patients in lesions of 50 mm. In one of these cases, an adenocarcinoma occurred after 8 months, which was managed surgically. Retrospective design, single center. This study supports the efficacy and safety of EMR-C for removing NADPs. Regular follow-up is mandatory because of the high risk of residual or recurrent adenomatous tissue and even cancer.

Ninety-Percent Distal Pancreatectomy

Context Brittle diabetes typically plagues the quality of life of patients after total pancreatectomy. Sparing even a small amount of endocrine tissue avoids extreme glycemic fluctuations, by maintaining a source of servo-regulated endogenous production of all pancreatic hormones (insulin, glucagon, somatostatin and pancreatic polypeptide). Objective We report on the outcome of a selected group of patients undergoing ninety-percent distal pancreatectomy (90% DP). Methods From April 2000 to May 2012, 90% DP was performed in 26 patients: 7 males (27%) and 19 females (73%), with a mean age of 68 years (range 40-79 years). Twenty-three patients underwent conventional open resection while 3 had a laparoscopic operation (robot-assisted in 2 of them). Splenectomy was associated in 24 patients (92%), while 2 had a multivisceral resection. Segmental resection of peripancreatic vessels was associated in 4 patients (1 celiac trunk-hepatic artery, and 3 superior mesenteric/portal vein). Results Seventeen patients were diagnosed with ductal adenocarcinoma (65%), 3 with well-differentiated endocrine tumor (12%), 3 with a serous cystadenoma, 1 with a mucinous cystadenocarcinoma (4%), 1 with carcinoma on IPMN, and 1 patient with chronic pancreatitis. Mean operative-time was 330 minutes (range 180-535 minutes). There was no post-operative mortality with a morbidity of 40%. Pancreatic fistula was recorded in 8 patients (32%) and was always managed conservatively. Thirteen patients developed insulin dependent diabetes mellitus (50%) and 16 developed exocrine insufficiency (61%) requiring enzyme supplementation. Conclusions 90% DP may be considered in patients with centrally located pancreatic lesions to avoid the complications due to pancreatic exocrine and endocrine insufficiency. In selected patients 90% DP may be performed laparoscopically, especially if robotic assistance is available. Careful patient selection and extended experience in pancreatic surgery are crucial to achieve the best results.

Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study

PurposeAs a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.Materials and MethodsWe collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.ResultsAlthough the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.ConclusionThe incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Factors Related to Long-Term Survival in Patients Affected by Well-Differentiated Endocrine Tumors of the Pancreas

Aim. To identify factors related to survival in patients affected by well-differentiated PETs (benign, uncertain behavior, and carcinoma) who underwent R0 pancreatic resection. Methods. Retrospective study of 74 consecutive patients followed up from January 1980 to December 2011. Prognostic factors were sex, age, type of tumor, presence of symptoms, type of surgical procedure, size of tumor, lymph nodes status, WHO classification, and TNM stage. Overall survival was evaluated using the Kaplan-Meier method. Cox regression analyses were used to identify the factors associated with prognosis in univariate and multivariate analysis. Results. The mean follow-up of all the patients was 106 ± 89 months. The 5–10-year long-term survival was 90.9% and 79.1%, respectively. At univariate analysis, patient age <55 years was significantly related to a better long-term survival compared to patients age ≥55 years (307 ± 15 months versus 192 ± 25 months; P = 0.010). Multivariate analysis showed that female gender (P = 0.006), patients without comorbidities (P = 0.033), and patients affected by well-differentiated benign pancreatic endocrine tumors (P = 0.008 and P = 0.002 in relation to tumors with uncertain behavior and carcinomas, resp.) were factors significantly related to a better long-term survival. Conclusions. Patients factors were strongly related to a better long-term survival in patients observed. WHO classification is a very useful prognostic tool for well-differentiated PETs.

Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor

Ataxia telangiectasia mutated kinase (ATM) and cyclin B1 are involved in cell cycle control. The prognostic significance of both molecules has not yet been investigated in pancreatic neuroendocrine tumors. The aim of this study was to evaluate the clinical and prognostic significance of ATM and cyclin B1 in patients with pancreatic neuroendocrine tumors. A total of 107 pancreatic neuroendocrine tumor specimens that were surgically resected were immunohistochemically investigated using the tissue microarray technique. Clinicopathologic results and survival were evaluated retrospectively. High expression of ATM and cyclin B1 was related to well-differentiated endocrine tumors of the World Health Organization (WHO) classification, but not related to TNM stages. The high ATM expression group (ATM ≥ 4) had a significantly smaller tumor size, lower recurrence rate, more number of functioning tumor, and well differentiation of WHO classification. The high cyclin B1 expression group (cyclin B1 ≥ 5) was related to smaller tumor size, less vascular invasion, less recurrence rate, and less death rate. However, cyclin B1 was the only significant factor for survival following multivariate analysis (p = 0.008; OR, 0.54; 95 % CI, 0.35-0.85). The current results suggested that expression of ATM and cyclin B1 may be useful markers to identify patients with poor prognosis who may benefit from close follow-up and aggressive therapy in pancreatic neuroendocrine tumors.

Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase‐2

Papillary thyroid carcinoma (PTC) is a well-differentiated endocrine malignant tumor that develops from thyroid follicular epithelium. The tumor represents the most common type of endocrine malignancy; however, its tumorigenesis is not fully elucidated. The aim of this study was to address the functional role of the sorting nexin (SNX) family in PTC because of recent experimental evidence suggesting that the SNX family members actively control endocytotic transportation as well as cell fate. Expression profiles of SNX family members of PTC showed a significant quantity of transcripts of SNX5. Further immunohistochemical analysis with an SNX5-specific monoclonal antibody established in this study consistently demonstrated the preferential expression of SNX5 in PTC (94.2%, 113/120 cases) as indicated by studies on 440 cases of various tumors. In contrast, other major carcinomas originating from the lung (2.6%, 1/38 cases), breast (5.1%, 2/39 cases), and intestine (4.2%, 1/24 cases) scarcely expressed SNX5. When we investigated models of murine thyroid tumors induced by the administration of carcinogens, high expression of Snx5 was also observed in well-differentiated thyroid tumors, further implying that the tumorigenesis of the thyroid gland was tightly associated with the abundance of SNX5/Snx5. Moreover epithelial cells expressing excess SNX5 showed high levels of Caspase-2 of an initiator caspase. Collectively these findings suggest that the evaluation of SNX5 expression would support pathological diagnosis of primary and secondary PTC.

EUS-FNA Diagnosis Cytology of Endocrine Tumor Recurrence

We examined a recurrent endocrine tumor patient who had undergone preoperative diagnosis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The cytomorphology and immunostaining patterns at onset were different from those seen at recurrence, and according to WHO classification we diagnosed the former condition as well-differentiated endocrine tumor and the latter condition as well-differentiated endocrine carcinoma. Endocrine tumors show great diversity of cytomorphology according to their malignancy, and we consider that understanding this is important to conducting cytoscreening diagnosis by cytomorphology.

Diffusion‐weighted MR imaging in pancreatic endocrine tumors correlated with histopathologic characteristics

To retrospectively assess apparent diffusion coefficients (ADCs) of different subtypes of pancreatic endocrine tumors based on the World Health Organization (WHO) classification system and analyze the potentially responsible histopathologic characteristics. Following Institutional Review Board (IRB) approval, 18 patients with surgical pathology-proven pancreatic endocrine tumors were evaluated. Tumors were subcategorized based on the WHO grading classification into well-differentiated tumors with benign and uncertain behavior and endocrine carcinomas with well and poor differentiation. ADCs were measured on diffusion-weighted (DW) images and compared using Student's t-test and one-way analysis of variance. The correlation between ADCs, tumor cellularity, Ki-67 labeling index (an index of cell growth), and extracellular fibrosis were analyzed. A difference was demonstrated in mean ADCs between well-differentiated endocrine tumors (1.75 ± 0.53) and endocrine carcinomas (1.00 ± 0.19 × 10(-3) mm(2) /sec) (P < 0.01). After excluding the three well-differentiated endocrine tumors with benign behavior and marked fibrosis, a significant inverse correlation between ADC values and cellularity of endocrine tumors was observed. An inverse correlation was seen between Ki-67 labeling index and ADC values (r = -0.70; P < 0.01). Tumor cellularity and/or extracellular fibrosis may account for various ADCs in pancreatic endocrine tumors. ADC correlates well with the Ki-67 labeling index and may help predict growth of endocrine tumors.

Pancreatic head well-differentiated endocrine tumor

The authors report a case of a small pancreatic head well-differentiated endocrine tumor. A 44-year-old woman was revealed to have a large cystic tumor in the pancreatic head area. Resection revealed a well-differentiated endocrine tumor 7 mm in diameter confined to the pancreatic head and obstructing the proximal portion of the pancreatic duct, resulting in cystic dilatation of the duct, mimicking a cystic tumor of the pancreatic head.

Pseudointraductal papillary mucinous neoplasia caused by microscopic periductal endocrine tumors of the pancreas: a report of 3 cases

Intraductal papillary mucinous neoplasms constitute histologically distinctive pancreatic tumors characterized by cystically dilated pancreatic ducts lined by papillary epithelium, often with extensive mucin production. With increasing awareness of and vigilance for these tumors, there has been a surge in the incidence of intraductal papillary mucinous neoplasms in the last few decades. However, resections of presumed intraductal papillary mucinous neoplasms sometimes reveal other types of cystic lesions. Here we describe 3 cases of small, incidentally identified pancreatic endocrine tumors that focally compressed the main pancreatic duct and presented clinically, radiologically, and grossly as intraductal papillary mucinous neoplasm. The histology of the dilated ducts in all cases lacked convincing features of intraductal papillary mucinous neoplasm, prompting more careful examination of the specimens and eventual identification of small well-differentiated endocrine neoplasms. The constellation of findings represented by pancreatic endocrine neoplasm-associated duct stricture and dilatation can mimic intraductal papillary mucinous neoplasm clinically and pathologically. Awareness of this phenomenon can potentially avoid misdiagnosis of intraductal papillary mucinous neoplasm in such cases.

Chromosome 3p alterations in pancreatic endocrine neoplasia

Pancreatic endocrine tumors (PET) are rare neoplasms classified as functioning (F-PET) or non-functioning (NF-PET) according to the presence of a clinical syndrome due to hormonal hypersecretion. PETs show variable degrees of clinical aggressiveness and loss of chromosome 3p has been suggested to be associated with an advanced stage of disease. We assessed chromosome 3p copy number in 113 primary PETs and 32 metastases by fluorescence in situ hybridization (FISH) using tissue microarrays. The series included 56 well-differentiated endocrine tumors (WDET), 62 well-differentiated endocrine carcinomas (WDEC), and 6 poorly differentiated endocrine carcinomas (PDEC). Chromosome 3p alterations were found in 23/113 (20%) primary tumors, with losses being predominant over gains (14% vs. 6%). Loss of 3p was found in 5/55 (9%) WDET, 11/52 (21%) WDEC, and never in PDEC. Gains of 3p were detected in 4/55 (7%) WDET, no WDEC, but notably in 3/6 (50%) PDEC (OR 23.6; P = 0.003). Metastases were more frequently monosomic for 3p compared to primary tumors (OR 3.6; P = 0.005). Monosomy was significantly associated with larger tumor size, more advanced tumor stage, and metastasis. No association was found with survival. Chromosome 3p copy number alterations are frequent events in advanced stage PET, with gains prevailing in PDEC while losses are more frequent in WDEC, supporting the view that a specific pattern of alterations are involved in these diverse disease subtypes.