Interobserver Variability in HER-2 Immunostaining Interpretation of Metastatic HER2 Low Breast Cancers in Cytology Specimens.

BACKGROUND: Approximately, 55% of breast carcinomas are reported to be HER-2 low breast carcinomas. Trastuzumab-Deruxtecan is a new FDA-approved targeted therapy for HER-2 low metastatic breast carcinomas, making it essential that all efforts are made to identify these tumors in specimens submitted for pathologic examination. Cytology specimens are often the first and only modality of this assessment due to the ease of specimen procurement. This study aimed to determine the variability in HER-2 immunostaining interpretation among observers using cytologic specimens from metastatic sites. DESIGN: A pathology database search was made to identify metastatic breast carcinoma reported in cytology specimens. A manual search was then done to identify cases of HER-2 low category, H&E cell block and HER-2 neu immunostain slides were retrieved for a total of 50 cases. Reviewer #1 and #2 independently interpreted HER-2 immunostain of all 50 cases. Only discordant cases were sent for reviewer-3 interpretation. All three were blinded by the metastatic site, and original HER-2 interpretation. RESULTS: Of 50 cases, 11 cases (22%) were reported as concordant scores between reviewer #1 and reviewer #2 but had a discordant original IHC report. Additionally, 4 cases (8%) had discordant reporting of HER2 IHC stain between reviewer #1 and reviewer #2 making a total of 15 cases (30%) with overall discordant results. CONCLUSION: This study highlights the interobserver variability of HER-2 immunostain interpretation for HER-2 low category of breast carcinomas. We recommend the need for more robust laboratory techniques including molecular for uniform identification of these unique targetable metastatic breast carcinoma groups.

Ten Years of Pathology on Twitter (X): Landscape and Evolution of Pathology on Twitter From 2012 to 2023.

CONTEXT.­: Social media is a powerful tool in pathology education and professional networking that connects pathologists and pathology trainees from around the world. Twitter (X) appears to be the most popular social media platform pathologists use to share pathology-related content and connect with other pathologists. Although there has been some published research on pathology-related activity on Twitter during short time frames, to date there has not been published research examining pathology-related Twitter activity in totality from its earliest days of activity to recently. OBJECTIVE.­: To comprehensively evaluate the use of pathology on Twitter (X) during the last 10 years. DESIGN.­: Pathology-related tweets were systematically scraped from Twitter from January 2012 to January 2023 using pathology hashtags as a surrogate measure for all pathology content on Twitter. COVID-related tweets were approximated by tweets containing the term "COVID." RESULTS.­: There were 591 812 unique pathology-related tweets identified during the time period, with #pathology being the most common hashtag used and #PathTwitter becoming more popular since 2020. There has been positive annual growth of pathology Twitter, with peaks in use during major pathology conferences. During the initial phases of the COVID-19 pandemic a sustained increase in pathology tweets was observed. CONCLUSIONS.­: Pathology Twitter has grown during the last 10 years and has become increasingly popular for pathology education and networking. With the changing landscape of social media platforms this study provides an understanding of how pathology medical education and professional networking uses of social media are used and evolve over time.

Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.

Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid and fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.

Significance of concurrent HPV testing with unsatisfactory Papanicolaou test for prediction of follow-up HPV, Papanicolaou test, and biopsy results.

OBJECTIVES: Approximately 1% to 2% of routine cytologic specimens collected for Papanicolaou testing are unsatisfactory for evaluation. The American Society for Colposcopy and Cervical Pathology 2019 guidelines recommend repeat testing within 2 to 4 months of an unsatisfactory Papanicolaou test (UPT) result. METHODS: We evaluated the utility of follow-up Papanicolaou testing, human papillomavirus (HPV) testing, and biopsy in 258 cases of UPTs. RESULTS: High-risk HPV testing was positive in 17.4% (n = 45) and negative in 82.6% (n = 213) of cases at the time of initial UPT; 8.1% (n = 21) of cases had discordant HPV test results. Similarly, 3.8% (n = 8) of initially HPV-negative cases were reported to be HPV-positive on follow-up; 28.9% (n = 13) of initially HPV-positive cases were reported to be HPV negative on follow-up. In total, 27.1% (n = 70) of cases underwent biopsy. Biopsies with significant findings were present in 40% (n = 12) of HPV-positive cases and 7.5% (n = 3) of HPV-negative cases. Low-grade squamous intraepithelial lesion (LSIL) (low-grade cervical intraepithelial neoplasia [CIN-1]) was the most significant finding in all 3 HPV-negative biopsies; 58.3% (n = 7) of HPV-positive biopsies showed LSIL (CIN-1), 13.3% (n = 4) showed HSIL (high-grade CIN), and 3.3% (n = 1) showed invasive carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of concurrent HPV testing at the time of UPT for predicting follow-up HPV test result within 1 year of initial UPT are 80.0%, 94.0%, 71.1%, and 96.2%, respectively. The sensitivity, specificity, PPV, and NPV of initial HPV test results for predicting follow-up Papanicolaou test results are 67.7%, 89.7%, 48.8%, and 95.0%, respectively. RESULTS: Concurrent HPV testing in the setting of UPT can be a sensitive tool for predicting follow-up HPV status and significant findings of squamous intraepithelial lesions on follow-up Papanicolaou tests and biopsy.

Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa is a common cause of pulmonary infection. As a Gram-negative pathogen, it can initiate a brisk and highly destructive inflammatory response; however, most hosts become tolerant to the bacterial burden, developing chronic infection. Using a murine model of pneumonia, we demonstrate that this shift from inflammation to disease tolerance is promoted by ketogenesis. In response to pulmonary infection, ketone bodies are generated in the liver and circulate to the lungs where they impose selection for P. aeruginosa strains unable to display surface lipopolysaccharide (LPS). Such keto-adapted LPS strains fail to activate glycolysis and tissue-damaging cytokines and, instead, facilitate mitochondrial catabolism of fats and oxidative phosphorylation (OXPHOS), which maintains airway homeostasis. Within the lung, P. aeruginosa exploits the host immunometabolite itaconate to further stimulate ketogenesis. This environment enables host-P. aeruginosa coexistence, supporting both pathoadaptive changes in the bacteria and the maintenance of respiratory integrity via OXPHOS.