Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

Trimyelia with divergent cord pathways and three foramina magni.

OBJECT: We report the rare finding of trimyelia with divergent cord pathways in a 33 5/7-week-old fetus who died shortly after spontaneous vaginal delivery. METHODS: The main autopsy findings were three separate and distinct spinal cords, arising from the medulla and exiting through three separate foramina magni. The two lateral cords coursed toward each upper extremity and the medulla split into two halves that rejoined to form a central cervical cord. Further evaluation of this anomaly revealed agenesis of the cerebellar vermis and cystic dilation of the fourth ventricle. Microscopic cross-sections of the two lateral cords demonstrated well-formed central canals, white matter, and central gray with motor neurons. Sections of the abnormal mid-cervical cord demonstrated abnormally structured cord parenchyma without central canals. CONCLUSIONS: Some features were consistent with iniencephaly; however, defects of the occipital bone, anterior spina bifida, and shortening of the spinal cord were absent. Although agenesis of the cerebellar vermis and cystic dilation of the fourth ventricle indicate Dandy-Walker syndrome, other features such as hydrocephalus, agenesis of the corpus callosum, infundibular hamartomas, and malformations of the inferior olives or an occipital encephalocele were absent. The possible pathogenesis of this intriguing pathological entity is briefly discussed.