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Extramammary metastases are uncommon and usually related to a poor prognosis, but the radiologist can suspect the diagnosis based on the patient's clinical history and specific imaging findings. Several imaging procedures may be used to evaluate breast metastases from different extramammary malignancies, including mammography, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography-CT (PET-CT). The clinical and imaging presentation of these metastases is contingent upon how the illness spreads, however, they have the potential to resemble either benign or malignant breast tumors. Metastases that disseminate hematologically tend to appear as a single round or oval mass with circumscribed margins. Sonographically, they are usually hypoechoic, and with CT or MRI, they usually enhance. Lymphatic dissemination, for example, frequently reveals significant asymmetry with skin thickening and diffuse breast edema, which is compatible with an inflammatory breast carcinoma. Knowing the many types of cancers that have the potential to spread to the breast as well as being able to accurately diagnose them is crucial to prevent a needless mastectomy and provide guidance for subsequent treatment. The purpose of this article is to provide a better understanding of the imaging features and immunohistochemistry (IHC) of secondary tumors of the breast by presenting eight distinctive cases, which will enable radiologists to recognize this entity.
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Neoplasias de la Mama , Imagen Multimodal , Femenino , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/secundario , Imagen Multimodal/métodos , Metástasis de la Neoplasia/diagnóstico por imagenRESUMEN
BACKGROUND: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. METHODS: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples. RESULTS: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01). CONCLUSIONS: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.
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Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Proteínas Tirosina Quinasas/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estudios Retrospectivos , Quinasa de Linfoma Anaplásico/genética , Proteínas Proto-Oncogénicas/genética , Adenocarcinoma/genética , Mutación , Receptores ErbB/genéticaRESUMEN
INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.
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Relevancia Clínica , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Biomarcadores de Tumor/metabolismo , Neoplasias Gástricas/patología , Estudios Prospectivos , PronósticoRESUMEN
Waldenström macroglobulinemia (WM) is a rare, indolent, and currently incurable B-cell neoplasm characterized by monoclonal immunoglobulin M gammopathy, frequent nodal involvement, and lymphoplasmacytic infiltration of the bone marrow. The clinical pattern at diagnosis is similar to that reported in developed countries but, unfortunately, the tools for a complete diagnosis and access to novel therapies are suboptimal. Older drugs such as bendamustine, cyclophosphamide, and chlorambucil may still play a role in treating WM. Prospective studies in resource-limited regions are required to further evaluate these essential aspects of the disease. In this document, we issue recommendations based on our local reality.
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Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/tratamiento farmacológico , Estudios Prospectivos , Ciclofosfamida/uso terapéutico , Inmunoglobulina M , Médula ÓseaRESUMEN
The most significant interest in veterinary oncology is occupied by tumors of a mixed nature, which are represented by the direct interaction of epithelial and mesenchymal components. According to some data, the formation of cell lineage of mesenchymal cells occurs due to the transformation of epidermal basket cells surrounding the glandular epithelium. In this case, the formation of a cartilage anlage with its further transformation into differentiated bone tissue occurs. The article contains information about the structure and features of the location and interaction of mixed tumors' glandular and stromal components in female dogs (n=29). It was revealed that in addition to simple mixed neoplasms, tumors with proplasia of the mesenchymal component into highly differentiated cartilage or bone tissue were also often registered. To confirm subcellular changes in the expression of certain types of proteins, such as a-SMA and vimentin, an IHC study was used. The expression of the studied biomarkers was established in mesenchymal fibroblastic differon cells and myoepithelial cells. The intensity of immunoreactive material expression ranged from moderate (2+) to strong (3+), indicating changes in myoepithelial cells' genotype during the formation of mixed mammary neoplasms.(AU)
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Animales , Femenino , Neoplasias Mamarias Animales/diagnóstico , Mioepitelioma/veterinaria , Vimentina/análisis , Biomarcadores de Tumor/análisis , PerrosRESUMEN
The direct-fluorescent antibody test (dFAT) is considered the "gold standard" assay to diagnose rabies. However, it is crucial to develop molecular techniques, such as RT-PCR and RT-qPCR, since many laboratories lack the needed supplies for performing complementary methods (viral isolation, for example). For this purpose, diagnostic techniques must be specific and sensitive to guarantee accuracy. This present investigation aimed to detect rabies virus (RABV) in 126 clinically suspected cattle in Brazil using different diagnostic tests [dFAT, mouse inoculation test (MIT), immunohistochemistry (IHC), RT-PCR and RT-qPCR] and to compare those results obtained under routine laboratory conditions. The results of the present investigation demonstrate that the molecular techniques are more sensitive and may detect low viral load, even though the non-homogeneous viral distribution caused a false-negative result in dFAT. We also observed a usual alteration in antigens distribution among regions of the central nervous system (CNS). By both dFAT and IHC assays, the most reliable CNS structures were thalamus and midbrain. Although this investigation demonstrated diagnostic sensitivity and specificity close to 100 % in all laboratory techniques employed, a dFAT auxiliary test is required for bovine specimens, such as molecular techniques, when there are poor sampling conditions (low viral load combined with unavailability of brainstem structures).
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Enfermedades de los Bovinos/diagnóstico , Técnicas de Laboratorio Clínico/métodos , Pruebas Inmunológicas/métodos , Rabia/diagnóstico , Rabia/veterinaria , Animales , Brasil , Bovinos , Enfermedades de los Bovinos/virología , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente Directa/métodos , Inmunohistoquímica/métodos , Ratones , Rabia/inmunología , Rabia/virología , Virus de la Rabia/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y Especificidad , Carga ViralRESUMEN
JUSTIFICATION: The prevalence of gastric cancer (GC) with increased expression of the HER2 oncoprotein shows important variations worldwide. Incidence and mortality rates of GC in Costa Rica are among the highest in Latin America and the world; however, the prevalence of HER2-positive cases in this country is unknown. Evaluation of this parameter is important to decide the therapeutic approach for GC patients. The aim of this study was to provide an estimation of the prevalence of GC patients overexpressing the HER2 oncogene in Costa Rica. METHODS: The investigation was carried out in two phases. The first one consisted of a retrospective review of 331 clinical records of patients diagnosed with advanced or metastatic GC from January 2010 to January 2012 in four hospitals in Costa Rica. In the second phase, immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) analyses were performed in formalin-fixed and paraffin-embedded (FFPE) surgical samples from 50 patients diagnosed with GC between 2012 and 2015. RESULTS: Of the 331 clinical files reviewed, the assessment of HER2 status was carried out in 62 patients (18.7%), of which only five (8%) were HER2-positive. In the 50 surgical specimens in which IHC and FISH analyses were performed, two of them (4%) presented overexpression and amplification of the HER2 oncogene. CONCLUSION: This study suggests that the prevalence of GC cases overexpressing the HER2 oncogene in Costa Rica is less than 8%. This is the first attempt ever undertaken to estimate the prevalence of HER2-positivity in GC in Costa Rica.
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Introducción: En los últimos años la inmunohistoquímica (IHQ) se ha convertido en el método más usado en la determinación de la expresión del receptor del factor de crecimiento epidérmico (REGF). La falta de control de algunos aspectos técnicos durante su determinación en muestras de tejidos fijados en formol e incluidos en parafina, como por ejemplo, la fijación tisular y el procesamiento de las muestras, la elección de un método adecuado de reanimación antigénica, el empleo de diferentes anticuerpos anti-REGF y sistemas de detección, a llegado a tal punto que la confiabilidad y reproducibilidad de la detección inmunohistoquímica de la sobreexpresión del REGF está siendo fuertemente cuestionada. Objetivo: La estandarización de estos procedimientos constituye una de las metas más perseguidas actualmente, con el objetivo de continuar empleando la sobreexpresión del REGF por IHQ como criterio de elección y predictor de la respuesta al tratamiento, sin necesidad de recurrir a técnicas más complejas para su detección, disminuyendo en gran medida a la variabilidad intra e interlaboratorios. Métodos: Revisión y determinación de la pertinencia en el control de la técnica investigativa y viabilidad de la misma. Conclusiones: La determinación de la sobreexpresión del REGF por IHQ continúa siendo el método más empleado actualmente como predictor de la respuesta a la terapia contra el receptor. La heterogeneidad de las muestras, la falta de estandarización de los procedimientos inmunohistoquímicos empleados, la existencia de numerosos protocolos con un mismo fin, así como otras fuentes de variabilidad, han conducido a la obtención de resultados poco confiables y reproducibles(AU)
Background: In recent years, immunohistochemistry (IHC) has become the most widely used method in determining the expression of epidermal growth factor receptor (EGFR). The lack of control of some technical aspects during their determination in formaldehyde fixed and paraffin embedded tissue such as tissue fixation and sample processing, the choice of a suitable antigen retrieval method, the use of different anti-EGFR antibodies and the detection systems have come to the point that the reliability and reproducibility of the imunohistochemical analysis of EGFR overexpression is being seriously questioned. Objective: The standardization of these procedures is one of most pursued goals at present, with the aim to continue using EGFR overexpression by IHC as selection criteria and predictor of treatment response, without resorting to most complex techniques for its detection, greatly diminishing the intra and inter laboratory variation. Methods: A review and determination of the relevance in the control of the investigative technique and its feasibility was made. Conclusions: The determination of EGFR overexpression by IHC continues being the most used method at present as predictor of the response to the therapy against the receptor. The heterogeneity of the samples, the lack of standardization of the most used immunohistochemical procedures, the existence of several protocols with the same goal, as well as other sources of variability have led to obtaining hardly reliable and reproducible results(AU)
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Factor de Crecimiento Epidérmico/análisisRESUMEN
Introducción: En los últimos años la inmunohistoquímica (IHQ) se ha convertido en el método más usado en la determinación de la expresión del receptor del factor de crecimiento epidérmico (REGF). La falta de control de algunos aspectos técnicos durante su determinación en muestras de tejidos fijados en formol e incluidos en parafina, como por ejemplo, la fijación tisular y el procesamiento de las muestras, la elección de un método adecuado de reanimación antigénica, el empleo de diferentes anticuerpos anti-REGF y sistemas de detección, a llegado a tal punto que la confiabilidad y reproducibilidad de la detección inmunohistoquímica de la sobreexpresión del REGF está siendo fuertemente cuestionada. Objetivo: La estandarización de estos procedimientos constituye una de las metas más perseguidas actualmente, con el objetivo de continuar empleando la sobreexpresión del REGF por IHQ como criterio de elección y predictor de la respuesta al tratamiento, sin necesidad de recurrir a técnicas más complejas para su detección, disminuyendo en gran medida a la variabilidad intra e interlaboratorios. Métodos: Revisión y determinación de la pertinencia en el control de la técnica investigativa y viabilidad de la misma. Conclusiones: La determinación de la sobreexpresión del REGF por IHQ continúa siendo el método más empleado actualmente como predictor de la respuesta a la terapia contra el receptor. La heterogeneidad de las muestras, la falta de estandarización de los procedimientos inmunohistoquímicos empleados, la existencia de numerosos protocolos con un mismo fin, así como otras fuentes de variabilidad, han conducido a la obtención de resultados poco confiables y reproducibles
Background: In recent years, immunohistochemistry (IHC) has become the most widely used method in determining the expression of epidermal growth factor receptor (EGFR). The lack of control of some technical aspects during their determination in formaldehyde fixed and paraffin embedded tissue such as tissue fixation and sample processing, the choice of a suitable antigen retrieval method, the use of different anti-EGFR antibodies and the detection systems have come to the point that the reliability and reproducibility of the imunohistochemical analysis of EGFR overexpression is being seriously questioned. Objective: The standardization of these procedures is one of most pursued goals at present, with the aim to continue using EGFR overexpression by IHC as selection criteria and predictor of treatment response, without resorting to most complex techniques for its detection, greatly diminishing the intra and inter laboratory variation. Methods: A review and determination of the relevance in the control of the investigative technique and its feasibility was made. Conclusions: The determination of EGFR overexpression by IHC continues being the most used method at present as predictor of the response to the therapy against the receptor. The heterogeneity of the samples, the lack of standardization of the most used immunohistochemical procedures, the existence of several protocols with the same goal, as well as other sources of variability have led to obtaining hardly reliable and reproducible results
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Adhesivos Tisulares/uso terapéutico , Inmunohistoquímica/métodos , Receptores ErbB , Investigación Biomédica/métodosRESUMEN
Schwannoma is a peripheral nerve sheath tumor (PNST), commonly found as a spindle cell tumor of autonomic nerves and rarely involving the skin of cattle. The present report describes the histopathology and immunohistochemistry features of a localized (solitary) benign PNST with final diagnosis of cutaneous schwannoma in a 4-year-old female Holstein bovine. The dome-shaped, well circumscribed, firm, non-smooth surfaced mass was composed of spindle-shaped cells arranged predominantly in interlacing fascicles or streams with a moderate to strong intervening collagenous stroma. Histopathologic changes included typical hypocellular areas with pale scant eosinophilic cytoplasm (Antoni B pattern) similar to myxomatous tissue, and hypercellular areas with deeply eosinophilic cytoplasm (non-typical Antoni A pattern) without nuclear palisading or Verocay bodies formation. Immunohistochemical reactions for S-100 protein, a Schwann cell marker, and vimentin were strong in the neoplastic cells. Other markers as desmin, neuron specific enolase (NSE), CD34, and p53 were all negative. It was concluded that concurrent evaluation of both histological and immunohistochemical features are required for the final diagnosis of schwannomas in domestic animals.(AU)