Strong Diagnostic Performance Research Articles

Comparing the performance of visual estimation and standard uptake value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography for detecting malignancy in pancreatic tumors other than invasive ductal carcinoma

The utility of FDG PET/CT for the detection and evaluation of invasive ductal carcinoma has been widely reported, but a few studies have assessed the utility of FDG PET/CT to detect malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. To compare the diagnostic performance of visual estimation with the semi-quantitative scores of FDG PET/CT for detecting malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. Images of pathologically proven pancreatic lesions from 32 patients were retrospectively evaluated: 14 benign lesions, 7 borderline (low malignant) lesions, and 11 malignant lesions. The average scores from visual estimation by the two observers were compared to two semi-quantitative analyses of FDG uptake in the lesions, namely the maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean). Visual analysis value, SUVmax and SUVmean were 0.33 ± 0.21, 1.8 ± 0.7 and 1.5 ± 0.7 for the benign lesions, 0.70 ± 0.28, 5.0 ± 2.6 and 3.1±1.7 for the borderline lesions, and 0.73 ± 0.18, 4.7 ± 2.5 and 3.2 ± 1.6 for the malignant lesions, respectively. Receiver operating characteristic analysis revealed the areas under the curves for detecting non-benign (malignant or borderline) lesions through visual analysis, SUVmax, and SUVmean were 0.914, 0.954, and 0.875, respectively. For a variety of pancreatic lesions other than invasive ductal carcinoma, visual analysis and semi-quantitative analyses all showed strong diagnostic performance. However, semi-quantitative analysis with SUVmax proved to be the most effective method for detecting non-benign pancreatic lesions.

Cerebrospinal Fluid Profiles of Amyloid β-Related Biomarkers in Alzheimer’s Disease

The amyloid cascade hypothesis on the pathogenesis of Alzheimer's disease (AD) states that amyloid β (Aβ) accumulation in the brain is a key factor that initiates the neurodegenerative process. Aβ is generated from amyloid precursor protein (APP) through sequential cleavages by BACE1 (the major β-secretase in the brain) and γ-secretase. The purpose of this study was to characterize APP metabolism in vivo in AD patients versus cognitively healthy subjects by examining alterations in cerebrospinal fluid (CSF) biomarkers. We measured BACE1 activity and concentrations of α- and β-cleaved soluble APP (sAPPα and sAPPβ, respectively) and Aβ40 in CSF, biomarkers that all reflect the metabolism of APP, in 75 AD patients and 65 cognitively healthy controls. These analytes were also applied in a multivariate model to determine whether they provided any added diagnostic value to the core CSF AD biomarkers Aβ42, T-tau, and P-tau. We found no significant differences in BACE1 activity or sAPPα, sAPPβ, and Aβ40 concentrations between AD patients and controls. A multivariate model created with all analytes did not improve the separation of AD patients from controls compared with using the core AD biomarkers alone, highlighting the strong diagnostic performance of Aβ42, T-tau, and P-tau for AD. However, AD patients in advanced clinical stage, as determined by low MMSE score (≤20), had lower BACE1 activity and sAPPα, sAPPβ, and Aβ40 concentrations than patients with higher MMSE score, suggesting that these markers may be related to the severity of the disease.

Evaluation of a Gene Expression Microarray-based Assay to Determine Tissue Type of Origin on a Diverse Set of 49 Malignancies

The Tissue of Origin Frozen (TOO-FRZ) assay from Pathwork Diagnostics has been cleared by the Food and Drug Administration as a diagnostic study for malignancies of unknown primary. The goal of this study was to evaluate the performance of TOO-FRZ on a diverse collection of malignancies. We collected a diverse set of 49 malignancies. We classified each case into 1 of 4 groups: common morphology from a tissue type included in the TOO-FRZ assay (n=29), uncommon morphology from a tissue type included in the TOO-FRZ assay (n=10), tumor from a tissue type not included in the TOO-FRZ assay (n=3), and malignancies of unknown primary (n=7). We found strong diagnostic performance for common morphologies from tissue types on the TOO-FRZ [overall accuracy=26 of 29 (90%, 95% CI, 73% to 97%)], with perfect performance in all tissue types except gastric (0 of 2) and pancreatic (1 of 2) tissues. There was a significant decline in performance for uncommon morphologies from tissue types included in the TOO-FRZ assay [6 of 10 (60%) cases with an indeterminate result, 1 of 10 (10%) cases with an incorrect prediction, and 3 of 10 (30%) with a correct prediction] and for tumors from tissue types not included in the assay (incorrect prediction in 2 of 3 cases). For the 7 malignancies of unknown primary in our study set, the TOO-FRZ provided a likely clinically useful result in only 2 of 7 cases. These results provide an insight into the strengths and limitations of this molecular assay for the surgical pathologist, and our findings suggest future directions for research in this area.