Clinicopathologic Features of Breast Carcinoma With 2018 American Society of Clinical Oncology/College of American Pathologists Fluorescence In Situ Hybridization Group 3 (Human Epidermal Growth Factor Receptor 2 Chromosome 17 Centromere Ratio <2.0 and Average Human Epidermal Growth Factor Receptor 2 Copy Number ≥6.0) Breast Cancers.

CONTEXT.­: The American Society of Clinical Oncology/College of American Pathologists 2018 update of the human epidermal growth factor receptor 2 (HER2) testing guideline includes a fluorescence in situ hybridization (FISH) group with a HER2 to chromosome 17 centromere (CEP17) ratio less than 2.0 and HER2 copy number 6.0 or greater (group 3), which requires integrated review of HER2 immunohistochemistry (IHC). OBJECTIVE.­: To assess the clinicopathologic features of group 3 patients and determine features associated with HER2-positive status after workup. DESIGN.­: Cases submitted for HER2 FISH between January 2019 and June 2022 were identified, and relevant clinicopathologic information was obtained. RESULTS.­: One hundred forty-two HER2 FISH cases (1.6%) were group 3. In 52 cases (36.6%) IHC was negative (0/1+), in 3 (2.8%) IHC was positive (3+), and in 86 (60.6%) IHC was 2+. Annotated IHC 2+ slides were recounted by a second reviewer in targeted areas, where 16 of 86 (18.6%) had a HER2:CEP17 ratio less than 2.0 and a HER2 copy number of 4.0 or greater to less than 6.0 (HER2 negative). After combined IHC/FISH review, 74 of 142 (52.1%) were classified as HER2 positive. HER2 copy number/cell was higher in HER2-positive compared with HER2-negative cases after the workup. The extent and intensity of staining in IHC 2+ cases did not correlate with the level of gene amplification. Twenty percent of HER2-positive patients achieved pathologic complete response. CONCLUSIONS.­: About half of group 3 cases were classified as HER2 positive after additional workup. Pathologic complete response rates in HER2-positive cases were lower than expected for group 1 (HER2:CEP17 ratio ≥2.0; HER2 copy number ≥4.0) patients. IHC targeted FISH recounts may be redundant and may potentially lead to classification of some patients as HER2 negative, resulting in withholding of targeted therapy.

Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.

OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC. METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD). RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC. CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

Quantitative Imaging Analysis Fluorescence In Situ Hybridization Validation for Clinical HER2 Testing in Breast Cancer.

CONTEXT.­: Quantitative imaging is a promising tool that is gaining wide use across several areas of pathology. Although there has been increasing adoption of morphologic and immunohistochemical analysis, the adoption of evaluation of fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue has been limited because of complexity and lack of practice guidelines. OBJECTIVE.­: To perform human epidermal growth factor receptor 2 (HER2) FISH validation in breast carcinoma in accordance with the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guideline. DESIGN.­: Clinical validation of HER2 FISH was performed using the US Food and Drug Administration-approved dual-probe HER2 IQFISH (Dako, Carpinteria, California) with digital scanning performed on a PathFusion (Applied Spectral Imaging, Carlsbad, California) system. Validation parameters evaluated included z-stacking, classifier, accuracy, precision, software, and hardware settings. Finally, we evaluated the performance of digital enumeration on clinical samples in a real-world setting. RESULTS.­: The accuracy samples showed a final concordance of 95.3% to 100% across HER2 groups 1 to 5. During clinical implementation for HER2 groups 2, 3, and 4, we achieved a final concordance of 76% (95 of 125). Of these cases, only 8% (10 of 125) had discordances with clinical impact that could be identified algorithmically and triaged for manual review. CONCLUSIONS.­: Digital FISH enumeration is a useful tool to improve the efficacy of HER2 FISH enumeration and capture genetic heterogeneity across HER2 signals. Excluding cases with high background or poor image quality and manual review of cases with ASCO/CAP group discordances can further improve the efficiency of digital HER2 FISH enumeration.

The process of social participation in primary health care: the case of Palencia, Guatemala.

BACKGROUND: In 2008, the World Health Organization issued a callback to the principles of primary health care, which renewed interests in social participation in health. In Guatemala, social participation has been the main policy for the decentralization process since the late 1990s and the social development council scheme has been the main means for participation for the country's population since 2002. AIM: The aim of this study was to explore the process of social participation at a municipal-level health commission in the municipality of Palencia, Guatemala. METHODS: Analysis of legal and policy documents and in-depth interviews with institutional and community-level stakeholders of the commission. RESULTS: The lack of clear guidelines and regulations means that the stakeholders own motivations, agendas and power resources play an important part in defining the roles of the participants. Institutional stakeholders have the human and financial power to make policies. The community-level stakeholders are token participants with little power resources. Their main role is to identify the needs of their communities and seek help from the authorities. Satisfaction and the perceived benefits that the stakeholders obtain from the process play an important part in maintaining the commission's dynamic, which is unlikely to change unless the stakeholders perceive that the benefit they obtain does not outweigh the effort their role entails. CONCLUSION: Without more uniformed mechanisms and incentives for municipalities to work towards the national goal of equitable involvement in the development process, the achievements will be fragmented and will depend on the individual stakeholder's good will.

Avances en el estudio sobre la estrongiloidosis / No disponible

La estrongiloidosis es una infección parasitaria de amplia distribución mundial, sobre todo en zonas tropicales y sub-tropicales. Strongyloides tiene varias especies de las cuales Strongyloides stercolaris y Strongyloides fulleborni son las únicas que tienen importancia en el hombre. S. stercolaris es un helminto de predominio intestinal, aunque puede diseminarse y producir elevada mortalidad en individuos inmuno-suprimidos. Estas características son observadas comúnmente en pacientes tratados con corticoides, portadores de neoplasias, transplantados o infectados con el virus HTLV-1. El diagnóstico puede ser difícil, ya que el examen de heces no siempre demuestra la presencia del parásito, el inmunodiagnóstico presenta alta sensibilidad pero baja especificidad y las técnicas moleculares están en estudio. El tratamiento se realiza con gran éxito utilizando ivermectina. La asociación de la parasitosis como infección oportunista en SIDA está todavía en discusión, así como la caracterización e importancia de moléculas potencialmente protectoras y utilizadas en un futuro como vacunas (AU)

Strongyloidosis is a world-wide distributed parasitic infection, mainly present in tropical and subtropical zones. Strongyloides includes several species, of which Strongyloides stercoralis and Strongyloides fuelleborni affect man. S. stercolaris mainly localizes in the intestine of its host, although it can give rise to a dispersed infection. Strongyloidosis is responsible of high mortality rates in immunosuppressed patients, e.g. patients treated with corticoids, carriers of neoplasias, transplanted or infected with HTLV-1 viruses. Diagnosis of strongyloidosis can be approached by fecal examination or by immunodiagnosis. Nevertheless, these methods lack sensitivity and specificity, respectively. Thus, other molecular technique are under study to improve strong yloidosis diagnosis. Regarding treatment, ivermectin is fully effective. The opportunistic behaviour of this parasitic infection in AIDS patients as well as the characterization and use of potentially protective molecules are still under study (AU)