Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9΀ (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be flexible enough to model isotropic scaling.

Context: Pathologists grade follicular lymphoma (FL) cases by selecting 10, random high power fields (HPFs), counting the number of centroblasts (CBs) in these HPFs under the microscope and then calculating the average CB count for the whole slide. Previous studies have demonstrated that there is high inter-reader variability among pathologists using this methodology in grading. Aims: The objective of this study was to explore if newly available digital reading technologies can reduce inter-reader variability. Settings and Design: In this study, we considered three different reading conditions (RCs) in grading FL: (1) Conventional (glass-slide based) to establish the baseline, (2) digital whole slide viewing, (3) digital whole slide viewing with selected HPFs. Six board-certified pathologists from five different institutions read 17 FL slides in these three different RCs. Results: Although there was relative poor consensus in conventional reading, with lack of consensus in 41.2% of cases, which was similar to previously reported studies; we found that digital reading with pre-selected fields improved the inter-reader agreement, with only 5.9% lacking consensus among pathologists. Conclusions: Digital whole slide RC resulted in the worst concordance among pathologists while digital whole slide reading selected HPFs improved the concordance. Further studies are underway to determine if this performance can be sustained with a larger dataset and our automated HPF and CB detection algorithms can be employed to further improve the concordance.

Background: The exponential use of the internet as a learning resource coupled with varied quality of many websites, lead to a need to identify suitable websites for teaching purposes. Aim: The aim of this study is to develop and to validate a tool, which evaluates the quality of undergraduate medical educational websites; and apply it to the field of pathology. Methods: A tool was devised through several steps of item generation, reduction, weightage, pilot testing, post-pilot modification of the tool and validating the tool. Tool validation included measurement of inter-observer reliability; and generation of criterion related, construct related and content related validity. The validated tool was subsequently tested by applying it to a population of pathology websites. Results and Discussion: Reliability testing showed a high internal consistency reliability (Cronbach's alpha = 0.92), high inter-observer reliability (Pearson's correlation r = 0.88), intraclass correlation coefficient = 0.85 and κ =0.75. It showed high criterion related, construct related and content related validity. The tool showed moderately high concordance with the gold standard (κ =0.61); 92.2% sensitivity, 67.8% specificity, 75.6% positive predictive value and 88.9% negative predictive value. The validated tool was applied to 278 websites; 29.9% were rated as recommended, 41.0% as recommended with caution and 29.1% as not recommended. Conclusion: A systematic tool was devised to evaluate the quality of websites for medical educational purposes. The tool was shown to yield reliable and valid inferences through its application to pathology websites.

Background: The cytology literature relating to diagnostic accuracy using whole slide imaging is scarce. We studied the diagnostic concordance between glass and digital slides among diagnosticians with different profiles to assess the readiness of adopting digital cytology in routine practice. Materials and Methods: This cohort consisted of 22 de-identified previously screened and diagnosed cases, including non-gynecological and gynecological slides using standard preparations. Glass slides were digitalized using Aperio ScanScope XT (×20 and ×40). Cytopathologists with (3) and without (3) digital experience, cytotechnologists (4) and senior pathology residents (2) diagnosed the digital slides independently first and recorded the results. Glass slides were read and recorded separately 1-3 days later. Accuracy of diagnosis, time to diagnosis and diagnostician's profile were analyzed. Results: Among 22 case pairs and four study groups, correct diagnosis (93% vs. 86%) was established using glass versus digital slides. Both methods more (>95%) accurately diagnosed positive cases than negatives. Cytopathologists with no digital experience were the most accurate in digital diagnosis, even the senior members. Cytotechnologists had the fastest diagnosis time (3 min/digital vs. 1.7 min/glass), but not the best accuracy. Digital time was 1.5 min longer than glass-slide time/per case for cytopathologists and cytotechnologists. Senior pathology residents were slower and less accurate with both methods. Cytopathologists with digital experience ranked 2 ^nd fastest in time, yet last in accuracy for digital slides. Conclusions: There was good overall diagnostic agreement between the digital whole-slide images and glass slides. Although glass slide diagnosis was more accurate and faster, the results of technologists and pathologists with no digital cytology experience suggest that solid diagnostic ability is a strong indicator for readiness of digital adoption.