Background: To assess reproducibility and accuracy of overall Nottingham grade and component scores using digital whole slide images (WSIs) compared to glass slides. Methods: Two hundred and eight pathologists were randomized to independently interpret 1 of 4 breast biopsy sets using either glass slides or digital WSI. Each set included 5 or 6 invasive carcinomas (22 total invasive cases). Participants interpreted the same biopsy set approximately 9 months later following a second randomization to WSI or glass slides. Nottingham grade, including component scores, was assessed on each interpretation, providing 2045 independent interpretations of grade. Overall grade and component scores were compared between pathologists (interobserver agreement) and for interpretations by the same pathologist (intraobserver agreement). Grade assessments were compared when the format (WSI vs. glass slides) changed or was the same for the two interpretations. Results: Nottingham grade intraobserver agreement was highest using glass slides for both interpretations (73%, 95% confidence interval [CI]: 68%, 78%) and slightly lower but not statistically different using digital WSI for both interpretations (68%, 95% CI: 61%, 75%; P = 0.22). The agreement was lowest when the format changed between interpretations (63%, 95% CI: 59%, 68%). Interobserver agreement was significantly higher ( P < 0.001) using glass slides versus digital WSI (68%, 95% CI: 66%, 70% versus 60%, 95% CI: 57%, 62%, respectively). Nuclear pleomorphism scores had the lowest inter- and intra-observer agreement. Mitotic scores were higher on glass slides in inter- and intra-observer comparisons. Conclusions: Pathologists’ intraobserver agreement (reproducibility) is similar for Nottingham grade using glass slides or WSI. However, slightly lower agreement between pathologists suggests that verification of grade using digital WSI may be more challenging.

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Addition of ganitumab to carboplatin paclitaxel chemotherapy in primary EOC did not improve progression-free survival.• Neutropenia, thrombocytopenia and hyperglycemia were more common in the ganitumab group when compared to the placebo group.• Patients with low expression of tumor IGFBP2 may have increased IGF bioavailability and may benefit from ganitumab.• Our results do not support further study of ganitumab in unselected EOC patients.

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Infection is a rare cause of orbital apex syndrome (OAS) and most commonly occurs in immunocompromised hosts. We report a case of OAS in an elderly immunocompetent female due to invasive aspergillosis and Staphylococcus aureus co-infection. The patient required both surgical debridement and prolonged courses of antibiotic and antifungal therapy. Invasive fungal disease must be considered in cases of OAS, even in patients without classic risk factors.