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Simple Summary: E-cadherin (CDH1 gene) germline mutations are associated with the development of the autosomal cancer syndrome known as hereditary diffuse gastric cancer. About 30% of families fulfilling the clinical criteria established by the International Gastric Cancer Linkage Consortium have constitutional alterations of the CDH1 gene. Different patterns of CDH1 germline mutations have described as truncating, deletion, insertion, splice site, non sense, silence, and at last, missense alterations. The frequency of the different E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has reported extremely variable. In this study we aimed to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from different geographical areas, using a systematic approach. Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease. [ABSTRACT FROM AUTHOR]

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC). [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the persistent issue of unequal access to medical imaging, with a particular focus on breast cancer screening and its impact on marginalized communities and racial/ethnic minorities. Central to our discussion is the role of scientific mobility among radiologists in fostering healthcare policy changes that promote diversity and cultural competence. We propose various strategies to bridge this gap, including cultural education, sensitivity training, and diversifying the radiology workforce. These measures aim to improve communication with diverse patient groups and reduce healthcare disparities. Additionally, we explore the challenges and advantages of teleradiology as a means to extend medical imaging services to underserved areas. In the context of artificial intelligence, we emphasize the critical need to validate algorithms across diverse populations to ensure unbiased and equitable healthcare outcomes. Overall, this paper underscores the importance of international collaboration in addressing global access barriers, presenting it as a key to mitigating disparities in medical imaging access and contributing to the pursuit of equitable healthcare. Access to medical imaging is pivotal in healthcare, playing a crucial role in the prevention, diagnosis, and management of diseases. However, disparities persist in this scenario, disproportionately affecting marginalized communities, racial and ethnic minorities, and individuals facing linguistic or cultural barriers. This paper critically assesses methods to mitigate these disparities, with a focus on breast cancer screening. We underscore scientific mobility as a vital tool for radiologists to advocate for healthcare policy changes: it not only enhances diversity and cultural competence within the radiology community but also fosters international cooperation and knowledge exchange among healthcare institutions. Efforts to ensure cultural competency among radiologists are discussed, including ongoing cultural education, sensitivity training, and workforce diversification. These initiatives are key to improving patient communication and reducing healthcare disparities. This paper also highlights the crucial role of policy changes and legislation in promoting equal access to essential screening services like mammography. We explore the challenges and potential of teleradiology in improving access to medical imaging in remote and underserved areas. In the era of artificial intelligence, this paper emphasizes the necessity of validating its models across a spectrum of populations to prevent bias and achieve equitable healthcare outcomes. Finally, the importance of international collaboration is illustrated, showcasing its role in sharing insights and strategies to overcome global access barriers in medical imaging. Overall, this paper offers a comprehensive overview of the challenges related to disparities in medical imaging access and proposes actionable strategies to address these challenges, aiming for equitable healthcare delivery. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides a comprehensive overview of mammary Paget disease (MPD) from its historical origins to the current diagnostic and treatment strategies while also exploring promising avenues for future advancements in the field. With improved understanding and ongoing research efforts, we aim to enhance the prognosis and quality of life for individuals affected by this relatively uncommon condition. Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple–areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening mammography reduces mortality from breast malignancy. However, breast cancer screening is, unfortunately, hindered due to the poor sensitivity of mammography in dense breasts: up to 15–30% of all cancers may be missed. Given the rapid development of Contrast-Enhanced Mammography (CEM) and its potential for diagnostic use, even in an asymptomatic population, it seems very important to correctly assess the Average Glandular Dose (AGD) for a single CEM examination. Few studies have compared the AGD of CEM versus Digital Mammography (DM) and protocols, including Digital Breast Tomosynthesis (DBT) plus DM, in the same group of patients. The additional role of tomosynthesis versus digital mammography in asymptomatic patients with dense breasts in screening examinations has been well investigated with encouraging results. In this study, we intend to compare the AGD and the diagnostic performance of CEM versus DM, and of CEM versus DM + DBT, performed in the same group of patients over the same period of time in a screening setting. This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Germline BRCA2 pathogenic variant carriers are associated with prostate cancer risk. Ashkenazi Jewish people are at higher risk of breast cancer due to the high prevalence of specific founder germline BRCA1/2 variants. The distribution of these variants (BRCA1 vs. BRCA2) in Ashkenazi men with prostate cancer is not clear. This systematic review and meta-analysis indicates that germline BRCA1 variants are higher in the Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi men. Instead, BRCA2 variants present a similar distribution between the two considered groups. Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene. [ABSTRACT FROM AUTHOR]

Simple Summary: Which should be the optimal surgical approach to breast cancer in the presence of high penetrance gene mutation represents a current clinical and scientific issue, lively debated and studied. Does inherited breast cancer always mean bilateral mastectomy? Scientific research is questioning the oncological safety of a conservative surgical approach in hereditary breast cancer. The present narrative review aims to explore the scientific panorama on this faceted and significant theme. Recent studies have demonstrated that hereditary breast cancer (BC) has a prevalence of 5–10% among all BC diagnoses. Nowadays, significant technological advances in the identification of an increasingly broad spectrum of genetic mutations allow for the discovery of an ever-growing number of inherited pathogenic (P) or likely pathogenic (LP) variants of breast cancer susceptibility genes. As the management of BC patients carrying mutations in the BRCA1/2 genes or other high-penetrance genes is currently a challenge, extensive research is being carried out and a lively scientific debate has been taking place on what the most appropriate local therapy, especially surgical treatment, of patients with inherited BC should be. In many studies, BC outcomes in BRCA carriers and non-carriers have been compared. A number of them showed that, when compared with mastectomy, breast-conserving surgery in BRCA patients is oncologically safe in terms of overall survival, although an increased risk of ipsilateral recurrence was reported. In these patients, devising a specific therapeutic strategy is an inevitably complex process, as it must take into consideration a series of factors, require a multimodal approach, guarantee personalization, strictly adhere to scientific international guidelines, and consider all available evidence. The present narrative review purposes to identify and illustrate evidence from significant selected studies that discussed those issues, as well as to suggest useful tools to clinicians managing this specific clinical condition in daily clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse gastric cancer is the hallmark of the hereditary diffuse gastric cancer syndrome related with the E-cadherin germline mutations. Other cancers (non-gastric) are described in association with the CDH1 gene germline alterations. In this study, we aimed to assess the overall frequency of CDH1 mutations in non-gastric tumors reported in literature so far. Hereditary Diffuse Gastric Cancer (HDGC) is a complex inherited syndrome caused by CDH1 germline mutations. DGC is the hallmark cancer of this genetic predisposition, but several other cancers are associated with these CDH1 mutations. In this review, we revised all studies reporting CDH1 mutations in non-GC patients. The selected studies included: (a) families aggregating with GC and other cancers, both, and (b) families presenting only non-gastric tumors association. Among non-gastric tumors, our results show that CDH1 mutations are most frequently identified in breast cancer. The frequency of missense mutations is higher in the non-GC group, as the age at diagnosis in this group. Moreover, the predominant CDH1 mutation affects the extracellular domain. Our data suggest that CDH1 genetic testing should be considered also in other cancers, especially breast tumors. [ABSTRACT FROM AUTHOR]