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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.

Triple-negative breast cancer, defined as that with negative expression of estrogen and progesterone receptors and cerbB2, accounted for 11% of invasive breast cancers in our study, drawn from an original cohort of 7048 women diagnosed with breast cancer from the files of the Department of Pathology, Singapore General Hospital, over 14 years. Women with triple-negative breast cancer were generally postmenopausal, with adverse pathological characteristics of high histological grade and frequent nodal metastases. Using a set of 61 invasive breast cancers earlier profiled into molecular subtypes with expression arrays, we defined specificity and sensitivity values for different immunohistochemical panels of basal keratins (CK5/6, CK14, CK17, 34 beta E12), CD117, EGFR, p63 and SMA in defining basal-like breast cancer. Subsequent application of a tri-panel of CK14, EGFR and 34 beta E12 (specificity 100% and sensitivity 78%) to our group of 653 triple-negative breast cancers delineated 84% to be basal-like. Immunohistochemical expression of individual biological markers correlated with unfavorable pathological parameters. We conclude that triple-negative breast cancers in an Asian population harbor adverse pathobiological features, and an immunohistochemical surrogate panel can be reliably used to define basal-like cancers among them.

Breast phyllodes tumors are rare fibroepithelial neoplasms that need to be distinguished from the common morphologically similar fibroadenomas, because phyllodes tumors can recur and progress to malignancy. Their potentially recurring and metastasizing behavior is attributed to their stromal characteristics, for which categorization between benign, borderline and malignant tumors have not been universally established. Previous clonality studies revealing monoclonal stromal cells versus a polyclonal epithelial component theorized that phyllodes tumors are mainly stromal neoplasms, possibly arising from fibroadenomas. More recent chromosomal imbalances in both epithelium and stroma have challenged this theory to favor neoplasia of both epithelium and stroma, with initial interdependence between the two components. Inverse correlations between epithelial and stromal overexpression for various biological markers like estrogen receptor, p53, c-kit, Ki-67, endothelin-1, epidermal growth factor receptor, heparan sulfate, in addition to findings of epithelial Wnt signalling with stromal insulin growth factors and beta-catenin expression, suggest an initial epithelial-stromal interdependence at the benign phase. Upon progression to malignancy, the stroma is hypothesized to assume an autonomous growth overriding any epithelial influence. Frequent genetic alterations are chromosomal gains of 1q and losses at chromosome 13. Acquisition of new genetic imbalances within the tumor consistent with intratumoral heterogeneity, and subclones within histologically benign phyllodes tumors that recur or metastasize are the current theories explaining these tumors' unpredictable clinical behavior.