Background Nonfunctioning adrenal incidentalomas are common and many patients undergo adrenalectomy to exclude adrenocortical carcinoma (ACC). Recent studies have shown dysregulated microRNA expression in ACC. The objective of this study was to determine the feasibility and diagnostic accuracy of measuring serum microRNAs in patients with benign and malignant adrenocortical tumors. Method Five microRNAs were selected from microRNA profiling studies in ACC (miR-let-7d, -34a, -195, -214, and 483-5p). Total microRNA was extracted from serum samples in patients with malignant and benign adrenal neoplasms. MicroRNAs levels were measured by quantitative RT-PCR and normalized to miR-16. To determine if microRNAs were secreted from ACC cells, we measured microRNA levels in culture. Results Serum samples from 22 patients with cortical adenomas and 17 patients with ACC were analyzed and all 5 microRNAs were detected. We found higher levels of miR-34a(p=0.001) and miR-483-5p(p=0.011) in patients with ACC. The AUC was 0.81 for miR-34a and 0.74 for miR-438-5p. MiR-34a and miR-483-5p levels in ACC cells were higher in the supernatant at 48 hours as compared to intracellular levels. Conclusions We show dysregulated microRNAs in ACC are detectable in human serum samples. MiR-34a and miR-483-5p are candidate serum biomarkers for distinguishing between benign and malignant adrenocortical tumors.

Introduction There is limited data on the utility of 6-18F-Fluoro-L-3,4-dihydroxyphenylalanine (18F-DOPA) and 18F-2-Deoxy-D-glucose (18F-FDG) in the workup of patients with pancreatic neuroendocrine tumors (PNETs). The aim of our study was to determine the accuracy of 18F-DOPA and 18F-FDG to detect PNETs in patients with von Hippel-Lindau disease (VHL). Methods 69 patients with a diagnosis of VHL and pancreatic lesion(s) were prospectively studied using CT, MRI, 18F-FDG, and 18F-DOPA. Clinical, genetic, and laboratory characteristics were analyzed to determine association with imaging study results. Results 40 patients underwent evaluation by all four modalities, 98 PNETs and 55 PNETs were identified on CT and MRI, respectively. Only 11 of the 98 lesions (11%) were positive on 18F-DOPA and 45 of the 98 (46%) lesions were positive on 18F-FDG. There were 13 18F-DOPA and 26 18F-FDG avid extra-pancreatic lesions. One patient underwent resection of an 18F-DOPA avid extra-pancreatic lesion in the lung, with pathology demonstrating a NET. There was no association between 18F-DOPA and 18F-FDG avidity and tumor size, age, sex, VHL mutation, or serum chromogranin A level. Conclusion 18F-FDG and MRI may be adjuncts to CT scan in identifying PNETs and metastatic disease. 18F-DOPA has limited value in identifying PNETs in patients with VHL but may be useful for identifying extra-pancreatic NET lesions.

Background The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing but only a subset of these heterogeneous tumors will progress to malignant disease which is associated with a poor prognosis. Currently, there is limited data on the natural history of these tumors and it is difficult to determine which patients require surgical intervention because the risk of metastatic disease cannot be accurately determined. Study Design We conducted a prospective study of 87 patients with von Hippel Lindau syndrome-associate solid pancreatic lesions to determine the natural history of these tumors with biochemical testing, follow up anatomic and functional imaging, and advanced imaging analysis with a median follow up of 4 years. Results Approximately 20% of consecutive tumor measurements during follow up were decreased in size and 20% showed no change. This included 2 of 4 surgically-proven malignant tumors which had a net decrease in tumor size over time. Tumor volume, as derived from greatest diameter and volumetric measurement, showed good correlation to pathology tumor measurement of surgically resected tumors (Spearman rank correlation ρ=0.72, p=0.0011, and ρ=0.83, p<0.0001; respectively). Tumor density measurement had an inverse relationship with tumor size (Spearman rank correlation −0.22, p=0.0047). A tumor density cutoff of 200 was 75% specific for malignant tumors. Conclusions PNETs demonstrate a non-linear growth pattern, which includes periods of no growth and apparent decrease in size by imaging. These growth patterns are variable and not associated with tumor grade and malignancy. Tumor density, as measured in this cohort, may offer a specific diagnostic tool for malignant disease.