Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver.

The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen’s Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654–0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667–0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R² = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

Objective: Breast cancer (BC) in non-Caucasian females is understudied and its management is based on Caucasian data. 30 % of the West Midlands females are non-Caucasian. We aimed to elucidate the pathologic features, molecular profile, and outcome of non-Caucasian breast cancer. Methods: Breast cancers (BCs) of different ethnic origins diagnosed at a large Birmingham tertiary referral hospital between 2000 and 2016 were identified. Detailed clinical and histological data were collected and statistically analyzed. Results: Out of 7554 BC cases, 749 were of ethnic ancestry and median age of 51 years. These comprised 47 in-situ and 702 invasive carcinomas of presenting symptomatically in 86.2% of patients. 53.4% of the invasive carcinomas measured >20 mm. Cancers were predominantly of grade 3 (45%), and grade 2 (42.4%). Median NPI was 4.35. 65.1% of the ethnic carcinomas were of luminal subtype, 18.6% were Her2 positive and 16.2% triple-negative. Median overall survival was 62 months. Five and ten-year survival was 81.7% & 68.4% respectively. Ethnicity correlated with higher NPI (p <0.001), larger tumour size (p= 0.001) and larger number of positive axillary nodes (p=0.007). Negative correlations were found between age at diagnosis and both invasive tumour size & grade (p< 0.001) and between tumour grade and overall survival (p= 0.006). Conclusion: Compared with Caucasian breast cancer, non-Caucasian tumours presented predominantly symptomatically at younger age, were of larger size, higher grade with more unfavorable phenotypes and shorter survival. This is important in counselling, planning management and follow up of non-Caucasian patients.

(2020). Juvenile ossifying fibroma of the maxilla presenting with proptosis and dystopia in a 4-year-old child. Orbit. Ahead of Print.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.