Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF (male to female) patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone.

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.

The human breast, as mentioned by Gudjonsson and co-authors

This study aims to present a series of cases reports of- knee arthritis occurring following COVID-19 RNA vaccination and to examine the potential role of these Spike protein-based RNA vaccines in the development of this arthritis. Although musculoskeletal disorders have been reported in connection with COVID-19 vaccines, post-vaccination arthritis is not yet listed. Given the different and specific mechanisms of Spike protein-based RNA vaccines and viral vector-based DNA vaccines, we report 7 cases that question the role of COVID-19 vaccines in the onset of early or late-onset knee arthritis observed following one or more injections. All patients (5 early onset and 2 late-onset cases) were examined in the same department and underwent a comprehensive assessment to investigate the usual causes of unilateral or bilateral oligoarthritis; none of them had a previous predisposition to rheumatic disease. No inflammatory rheumatic disease was detected, nor did any develop after a follow-up period of at least 24 months. A double-check of medical histories (both prior to and following diagnosis) was carried out by consulting the general medical database for all patients described. Post-vaccination serological monitoring of blood and synovial fluid to detect the presence of anti-spike antibodies has been requested for all patients and a synovial biopsy was performed in four of them. All patients showed improvement following low-dose prednisolone treatment within two months, but in some patients the symptoms persist. Anti-Spike antibody levels were found to be elevated in blood and synovial fluid samples from all patients. Synovial biopsies reveal chronic histiocytic (CD68+) and plasmocytic infiltration (CD3+) accompanied by neovascularisation. The similar timeline, progression and clinical manifestations of this knee arthritis might suggest a pathogenic role for the spike protein and/or an overproduction of anti-spike antibodies following mRNA vaccination.