The study evaluated morphologic patterns, mutational profiles, and β-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n = 19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for β-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n = 90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. β-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P = 0.02). Mucinous differentiation (MD) was associated with KRAS mutations (Po0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ = 0.82), whereas agreement on MD was weak (κ = 0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with
Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a dementia-related proteinopathy common in the elderly population. LATE-NC stages 2 or 3 are consistently associated with cognitive impairment. A condensed protocol (CP) for the assessment of Alzheimer disease neuropathologic change and other disorders associated with cognitive impairment, recommended sampling of small brain portions from specific neuroanatomic regions that were consolidated, resulting in significant cost reduction. Formal evaluation of the CP for LATE-NC staging was not previously performed. Here, we determined the ability of the CP to identify LATE-NC stages 2 or 3. Forty brains donated to the University of Washington BioRepository and Integrated Neuropathology laboratory with known LATE-NC status were resampled. Slides containing brain regions required for LATE-NC staging were immunostained for phospho-TDP-43 and reviewed by 6 neuropathologists blinded to original LATE-NC diagnosis. Overall group performance distinguishing between LATE-NC stages 0–1 and 2–3 was 85% (confidence interval [CI]: 75%–92%). We also used the CP to evaluate LATE-NC in a hospital autopsy cohort, in which LATE-NC was more common in individuals with a history of cognitive impairment, older age, and/or comorbid hippocampal sclerosis. This study shows that the CP can effectively discriminate higher stages of LATE-NC from low or no LATE-NC and that it can be successfully applied in clinical practice using a single tissue block and immunostain.
Creutzfeldt-Jakob disease (CJD) is a complex and rapidly fatal prion infection of the central nervous system with characteristic clinical and pathological findings. Herein, we present the case of an 80-year-old man with a 2-month history of rapid cognitive decline and ataxic gait. He was found to have a positive rapid plasma reagin and fluorescent treponemal antibody absorption (FTA-ABS) upon clinical testing and was presumed to have neurosyphilis. His neurological status precipitously declined during his hospitalization and he died. A complete autopsy was performed, which revealed diffuse spongiform change throughout the cerebrum. Brain tissue was sent to the National Prion Disease Surveillance Center, where immunostaining for prion protein (3F4) showed granular deposits, confirming the diagnosis of CJD. There have been rare cases reported in which CJD was clinically suspected but neurosyphilis was confirmed at autopsy. To our knowledge, this is the first case to be published in which the clinical findings strongly favored neurosyphilis, but spongiform encephalopathy was identified at autopsy. We review the clinical, radiographic, electrophysiological, laboratory, and histopathological features of both diseases and discuss the overlapping findings and inherent diagnostic difficulties. We also review the recommended protocols for safely handling suspected prion-infected autopsy tissue. A heightened awareness of the features of CJD and other prion diseases is needed among forensic pathologists, neuropathologists, and general autopsy pathologists to understand how to safely handle the tissue to get definite diagnoses for the decedent's family members and clinical care team.
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