Citations

Context.— Distinguishing between renal oncocytic tumors, such as renal oncocytoma (RO), and a subset of tumors with overlapping characteristics, including the recently identified low-grade oncocytic tumor (LOT), can present a diagnostic challenge for pathologists owing to shared histopathologic features. Objective.— To develop an automatic computational classifier for stratifying whole slide images of biopsy and resection specimens into 2 distinct groups: RO and LOT. Design.— A total of 269 whole slide images from 125 cases across 6 institutions were collected. A weakly supervised attention-based multiple-instance–learning deep learning (DL) model was trained and initially evaluated through 5-fold cross validation with case-level stratification, followed by validation using an independent holdout data set. Quantitative performance evaluation was based on accuracy and the area under the receiver operating characteristic curve (AUC). Results.— The developed model data set yielded generalizable performance, with a 5-fold average testing accuracy of 84% (AUC = 0.78), and a closely aligning accuracy of 83% (AUC = 0.92) on the independent holdout data set. Conclusions.— The proposed artificial intelligence approach contributes toward a comprehensive solution for addressing commonly encountered renal oncocytic neoplasms, encompassing well-established entities like RO along with the challenging “gray zone” LOT, thereby proving applicable in clinical practice.

Abstract Given the heterogeneous clinical behavior of pancreatic neuroendocrine tumors (pNETs), improved prognostic markers are needed to guide management and post‐resection surveillance. Patients who underwent resection of large (≥3 cm) sporadic well‐differentiated pNETs from 2000 to 2019 were identified. The Ki‐67 proliferation index was determined using immunohistochemistry, and alternative lengthening of telomeres (ALT) status was assessed using fluorescence in situ hybridization. Recurrence‐free and overall survival were estimated using Kaplan–Meier analysis. Multivariable Cox regression analysis evaluated factors associated with recurrence‐free survival. A total of 106 patients were identified. ALT was positive in 57 (54%) and negative in 49 (46%). Ki‐67 was ≥3% in 74 (70%) and <3% in 32 (30%). Tumors with Ki‐67 ≥3% were more likely to be ALT positive (61% vs. 38%, p = .046). Stratifying by ALT status and Ki‐67 proliferation index, median recurrence‐free survival was 4.6 years for patients with ALT‐positive/Ki‐67 ≥3% tumors, 3.1 years for patients with ALT‐positive/Ki‐67 <3% tumors, 12.4 years for patients with ALT‐negative/Ki‐67 ≥3% tumors, and 20.2 years for patients with ALT‐negative/Ki‐67 <3% tumors ( p < .001). Initial recurrence was distant in 82% and locoregional in 18%. Across all groups, overall survival was similar ( p = .19). In multivariable analysis, advanced age, ALT positivity, perineural invasion, and lymph node metastases were associated with increased recurrence risk (all p < .05). ALT and Ki‐67 provide complementary information on post‐resection recurrence risk, which can guide subsequent surveillance and management strategies. These data support the incorporation of ALT testing into routine clinical practice.

AbstractCases of myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) co‐occurring with neoplasms have been reported. In this international, retrospective cohort study in South Korea and the USA, 16 of 445 (3.6%) patients with MOGAD had concurrent neoplasm within 2 years of MOGAD onset, resulting in a standardized incidence ratio for neoplasm of 3.10 (95% confidence interval [CI], 1.77–4.81; P < 0.001) when compared to the age‐ and country‐adjusted incidence of neoplasm in the general population. However, none of the nine tumor tissues obtained demonstrated MOG immunostaining. The slightly increased frequency without immunohistopathological evidence suggest with true paraneoplastic MOGAD is extremely rare.

Abstract The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and nongenetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography.

Abstract The radiation sensitivity index (RSI) and 12-chemokine gene expression signature (12CK GES) are two gene expression signatures (GES) that were previously developed to predict tumor radiation sensitivity or identify the presence of tertiary lymphoid structures in tumors, respectively. To advance the use of these GESs into clinical trial evaluation, their assays must be assessed within the context of the Clinical Laboratory Improvement Amendments (CLIA) process. Using HG-U133Plus2.0 arrays, we first established CLIA laboratory proficiency. Then the accuracy (limit of detection and macrodissection impact), precision (variability by time and operator), sample type (surgery vs. biopsy), and concordance with a reference laboratory were evaluated. RSI and 12CK GES were reproducible (RSI: 0.01 mean difference, 12CK GES: 0.17 mean difference) and precise with respect to time and operator. Taken together, the reproducibility analysis of the scores indicated a median RSI difference of 0.06 (6.47% of range) across samples and a median 12CK GES difference of 0.92 (12.29% of range). Experiments indicated that the lower limit of input RNA is 5 ng. Reproducibility with a second CLIA laboratory demonstrated reliability with the median RSI score difference of 0.065 (6% of full range) and 12CK GES difference of 0.93 (12% of observed range). Overall, under CLIA, RSI and 12CK GES were demonstrated by the Moffitt Cancer Center Advanced Diagnostic Laboratory to be reproducible GESs for clinical usage. Significance: The RSI and 12CK GES are two GESs that predict tumor radiation sensitivity or the presence of tertiary lymphoid structures in tumors, respectively. These GESs were assessed within the CLIA process for future clinical use. We established proficiency, reproducibility, and reliability characteristics for both signatures in a controlled setting, indicating these GESs are suitable for validation within future clinical trials.

Abstract Pancreatic neuroendocrine neoplasm (panNEN) is a rare malignancy and the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma (PDAC), but its etiology is poorly understood. We investigated whether the risk factors of panNEN are concordant with those known for PDAC. We performed the largest case-control study to date on panNENs, comprising 927 sporadic nonfunctional panNEN cases and 1807 frequency-matched controls, using data from the Mayo Clinic Biospecimen Resource for Pancreas Research. We assessed associations for obesity, first-degree family history of pancreatic cancer, cigarette smoking, overall type II diabetes mellitus (T2DM), new-onset T2DM (&lt;1 year before panNEN diagnosis), longstanding T2DM (≥5 years), alcohol intake and aspirin use. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). Our results show that overall T2DM (OR = 1.71, 95% CI: 1.37–2.14) and new-onset T2DM (OR = 2.65, 95% CI: 1.92–3.69) are associated with higher odds of panNEN, but not longstanding T2DM (OR = 1.29, 95% CI: 0.94–1.75). A non-significant elevated odds of panNEN was observed among participants with a positive family history of pancreatic cancer (OR = 1.44, 95% CI: 0.96–2.14). Alcohol use was inversely related to panNEN (OR = 0.52, 95% CI: 0.42–0.66, ever-vs-never). No association was observed for smoking, obesity or aspirin use. These findings indicate that overall T2DM and new-onset T2DM are associated with higher odds of panNEN. Unlike PDAC, alcohol use was inversely related to panNEN, and we found no associations for cigarette smoking, obesity or aspirin use. These results indicate differences in the risk factor profiles of panNEN and PDAC.