Incidental neuroendocrine tumors of the pancreas: MDCT findings and features of malignancy.

OBJECTIVE: The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome, and determine the incidence of "nonbenign" behavior. MATERIALS AND METHODS: In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence. RESULTS: A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence. CONCLUSION: Approximately 50% of incidental NETs show uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence.

Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes.

OBJECTIVE: Invasive cancers arising from intraductal papillary mucinous neoplasm (IPMN) are recognised as a morphologically and biologically heterogeneous group of neoplasms. Less is known about the epithelial subtypes of the precursor IPMN from which these lesions arise. The authors investigate the clinicopathological characteristics and the impact on survival of both the invasive component and its background IPMN. DESIGN AND PATIENTS: The study cohort comprised 61 patients with invasive IPMN (study group) and 570 patients with pancreatic ductal adenocarcinoma (PDAC, control group) resected at a single institution. Multivariate analyses were performed using a stage-matched Cox proportional hazard model. RESULTS: The histology of invasive components of the IPMN cohort was tubular in 38 (62%), colloid in 16 (26%), and oncocytic in seven (12%). Compared with PDAC, invasive IPMNs were associated with a lower incidence of adverse pathological features and improved mortality by multivariate analysis (HR 0.58; 95% CI 0.39 to 0.86). In subtype analysis, this favourable outcome remained only for colloid and oncocytic carcinomas, while tubular adenocarcinoma was associated with worse overall survival, not significantly different from that of PDAC (HR 0.85; 95% CI 0.53 to 1.36). Colloid and oncocytic carcinomas arose only from intestinal- and oncocytic-type IPMNs, respectively, and were mostly of the main-duct type, whereas tubular adenocarcinomas primarily originated in the gastric background, which was often associated with branch-duct IPMN. Overall survival of patients with invasive adenocarcinomas arising from gastric-type IPMN was significantly worse than that of patients with non-gastric-type IPMN (p=0.016). CONCLUSIONS: Tubular, colloid and oncocytic invasive IPMNs have varying prognosis, and arise from different epithelial subtypes. Colloid and oncocytic types have markedly improved biology, whereas the tubular type has a course that resembles PDAC. Analysis of these subtypes indicates that the background epithelium plays an equally, if not more, important role in defining the biology and prognosis of invasive IPMNs.

Predictors of the presence of concomitant invasive ductal carcinoma in intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVE: Invasive ductal carcinoma (DC) of the pancreas arising as an independent lesion in association with intraductal papillary mucinous neoplasm (IPMN) has occasionally been reported. However, clinicopathological features related to the presence of DC in patients with IPMN remain largely unknown. The purpose of the present study was to determine the factors predicting the presence of concomitant DC in those with IPMN. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological data of a consecutive series of 236 patients with IPMN treated by surgical resection or followed up at our institution between January 1987 and June 2008. In an attempt to identify predictors for the presence of DC, clinicopathological variables were compared between IPMN patients with concomitant DC and those without concomitant DC. RESULTS: Of 236 patients with IPMN, concomitant DC was detected synchronously or metachronously in 22 patients (9.3%). All the 22 IPMNs were of branch duct type and histological grades of 12 resected IPMNs were adenoma(n = 8) and borderline (n = 4). Multivariate analysis revealed 2 significant predictive factors for the presence of DC in IPMN, including worsening diabetes mellitus (P < 0.001) and an abnormal serum CA 19-9 level (P = 0.024). CONCLUSION: In view of the high prevalence of DC careful inspection of the entire pancreatic gland is necessary for early detection of DC in patients with branch duct IPMNs, especially when worsening diabetes mellitus and an abnormal serum CA 19-9 level are manifested.

Survival in ampullary cancer: potential role of different KRAS mutations.

OBJECTIVE: The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however, a subset of AA have poor biology and outcomes similar to pancreatic cancer. Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome. METHODS: The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and χ(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively. RESULTS: A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival ≤30 months were labeled "high-risk." Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage. CONCLUSION: The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy.

Cystic pancreatic neuroendocrine tumors: the value of cytology in preoperative diagnosis.

BACKGROUND: Cystic pancreatic neuroendocrine tumors (cPanNETs) account for 13% to 17% of PanNETs. Although the value of endoscopic ultrasound (EUS) imaging and cyst fluid analysis (CFA) in their preoperative diagnosis has been well described, limited information is available about the diagnostic role of cytology samples obtained from fine-needle aspiration (FNA). METHODS: Cytopathology records between 1992 and 2013 were searched for all reports of cysts interpreted as PanNET. Patient demographics, clinical and radiologic information, CFA, histopathology, and cytopathology findings were recorded. Performance characteristics of cytology and EUS for the accurate diagnosis of cPanNET were calculated. RESULTS: In total, 35 FNAs from 33 patients with cPanNETs were identified, and 34 EUS were performed. Cytology made a specific diagnosis of a cPanNET in 71% of the biopsies compared with a specific diagnosis by EUS in 38% of cases. An interpretation of suspicious for cPanNET was given in 77% of cases by cytology and in 47% by EUS. Cytology identified 86% of the lesions as high-risk pancreatic cysts compared with 56% by EUS. Diagnostic morphology was present on both cytology and cell block preparations in 60% of aspirates, on cytology only in 20%, and on cell block only in 20%. CFA was performed on 51% cyst fluids. All cysts but 1 revealed low carcinoembryonic antigen levels (range, 0.2 to >500 ng/mL; mean, 29.5 ng/mL), and amylase levels were <500 U/L in all but 2 cases (range, 16-1493 U/L; mean, 205 U/L). CONCLUSIONS: Cytology is the most accurate test for preoperative diagnosis of cPanNETs. EUS is insufficiently accurate for independent diagnosis, and carcinoembryonic antigen and amylase analyses are noncontributory.

Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes.

OBJECTIVES: To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs). DESIGN: Case series. SETTING: Academic hospital. PATIENTS: Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009. MAIN OUTCOME MEASURES: Operative morbidity and survival after resection. RESULTS: A total of 139 patients with median age of 56 years (range, 21-85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P = .01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P < .001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival. CONCLUSIONS: Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning PETs should undergo tumor resection and careful postoperative surveillance, even if surgical pathologic findings suggest benign disease.