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Purpose: This study aimed to assess the concordance of human epidermal growth factor receptor 2 (HER2) expression scoring by immunohistochemistry (IHC) among practicing pathologists in Japan, given the challenging nature of scoring and the critical role of HER2 status in breast cancer management., Methods: Whole slide images (WSI) from 20 invasive breast cancer cases (1 representative WSI per case) selected to represent a diverse IHC scores and staining patterns were used in an online survey involving seven reference pathologists who established consensus HER2 IHC scores (0 to 3 +) decided by majority interpretation. Participating pathologists nationwide scored the same 20 WSI cases online using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guidelines. Deidentified case metadata were registered in the uPath system., Results: A total of 144 participating pathologists responded. The scoring results of the participating pathologists most commonly agreed with the consensus IHC score, followed by a ± 1 point deviation and no survey responses with > 1 point deviation. The mean percentage of agreement with the consensus score for all 20 cases was 63.4%. In cases where the reference pathologists' scores were discordant, the participating pathologists also showed a lower concordance rate., Conclusion: This study highlighted the current status of HER2 expression scoring by IHC for breast cancer among pathologists in Japan. These findings underscore the challenges in HER2 IHC scoring cases and emphasize the need for improved standardization and training, especially in the evolving landscape of HER2-targeted therapies., (© 2024. The Author(s).)

Introduction: Medullary breast carcinomas (MBCs) are distinguished by circumscribed, high-grade morphology with dense chronic inflammation; they are associated with the basal phenotype but have a relatively good prognosis., Methods: This study aimed to review the clinicopathological features of MBCs diagnosed at the Department of Pathology, Singapore General Hospital and correlate them with immunohistochemical expression of hormonal markers and c-erbB-2, the basal markers p53, cytokeratin (CK) 14, epidermal growth factor receptor (EGFR) and 34BE12, and the follow-up outcome., Results: Using Ridolfi's criteria for histologic reviews, 62 patients previously diagnosed as having 'typical MBC' (n = 26), 'atypical MBC' (n = 32) and 'invasive carcinoma with focal medullary-like features' (n = 4) were re-classified as follows: 'typical MBC' (n = 6; 9.7%), 'atypical MBC' (n = 46; 74.2%), and 'non-medullary infiltrating carcinoma' (n = 10; 16.1%). Clinicopathological parameters, including ethnicity, age, tumour size and concurrent ductal carcinoma in situ (DCIS), showed no statistically significant correlation with review diagnoses and immunohistochemical findings. Presence of lymphovascular invasion and nodal stage were significantly correlated with recurrence and breast cancer-related deaths, respectively. ER negativity was significantly correlated with triple positivity for basal markers CK14, EGFR and 34BE12, which comprised patients who showed a significantly decreased disease-free survival rate within a 10-15-year follow-up period., Conclusions: Lymphovascular invasion and high nodal stage as well as triple negativity among typical and atypical MBCs that have basal-like phenotype represent a portion of invasive carcinomas with medullary features that may have poor outcomes in this otherwise relatively good prognostic group., Competing Interests: None

Background: Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers., Methods: Quantitative scoring of Ki67 on tissue microarray (TMA) sections of 440 invasive breast cancers was performed using Aperio ePathology ImmunoHistochemistry Nuclear Image Analysis algorithm, with TMA slides digitally scanned via Aperio ScanScope XT System., Results: On multivariate analysis, tumours with Ki67 ≥14% had an increased likelihood of recurrence (HR 1.941, p=0.021) and shorter overall survival (HR 2.201, p=0.016). Similar findings were observed in the subset of 343 ER positive breast cancers (HR 2.409, p=0.012 and HR 2.787, p=0.012 respectively). The value of Ki67 associated with ER+HER2-PR<20% tumours (Luminal B subtype) was found to be <17%., Conclusion: Using CAIA, we found optimal thresholds for Ki67 that predict a poorer prognosis and an association with the Luminal B subtype of breast cancer. Further investigation and validation of these thresholds are recommended., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: It is unclear as to whether the size ratio elastographic technique is useful for assessing ultrasound- detected ductal carcinoma-in-situ (DCIS) masses since they commonly lack a significant desmoplastic reaction. The objectives of this study were to determine the accuracy of this elastographic technique in DCIS and examine if there was any histopathological correlation with the grey-scale strain patterns., Materials and Methods: Female patients referred to the radiology department for image-guided breast biopsy were prospectively evaluated by ultrasound elastography prior to biopsy. Histological diagnosis was the gold standard. An elastographic size ratio of more than 1.1 was considered malignant. Elastographic strain patterns were assessed for correlation with the DCIS histological architectural patterns and nuclear grade., Results: There were 30 DCIS cases. Elastographic sensitivity for detection of malignancy was 86.7% (26/30). 10/30 (33.3%) DCIS masses demonstrated predominantly white elastographic strain patterns while 20/30 (66.7%) were predominantly black. There were 3 (10.0%) DCIS masses that showed had a co-existent bull's-eye sign and 7 (23.3%) other masses had a co-existent toothpaste sign, a strain pattern that has never been reported in the literature. Four out of 4/5 comedo DCIS showed a predominantly white strain pattern (p=0.031) while 6/7 cases with the toothpaste sign were papillary DCIS (p=0.031). There was no relationship between the strain pattern and the DCIS nuclear grade., Conclusions: The size ratio elastographic technique was found to be very sensitive for ultrasound-detected DCIS masses. While the elastographic grey-scale strain pattern should not be used for diagnostic purposes, it correlated well with the DCIS architecture.