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OBJECTIVE: The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse. DESIGN: Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system. PATIENTS AND MEASUREMENT: After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis. CONCLUSIONS: Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence.
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Recidiva Local de Neoplasia , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Fatores de Risco , Idoso , Radioisótopos do Iodo/uso terapêutico , PrognósticoRESUMO
OBJECTIVE: There is beauty in cytopathology. That beauty and art can be transmitted and shared through fun images on social media. METHODS: As social media becomes more popular, pathologists and related professionals have started to share the images that they capture at work on their profiles, tagging them with the hashtag #Pathart. #Pathart hashtag unites two concepts innately related: Pathology and art. RESULTS: When groups of pathologists share concurring ideas, the result is an explosion of creativity that spreads even to new professionals and students. In addition, it attracts the attention of people, dedicated to other subjects such as journalism, who, with their interactions, give visibility to our field. This helps counteract the stereotypes and gives people a better understanding of what we do and why it is important. Therefore, the more pathologists and related professionals meet and interact with each other, the better. CONCLUSIONS: #Pathart images raise great interest among professionals, which contributes to the creation of a united and strong community of pathologists some of whom are dedicated to cytology. Interaction and professional collaboration between these professionals can positively contribute to disseminating scientific content and creating work/research groups. This might have an impact, both direct and indirect, on improving the quality of diagnoses and treatments in our patients.
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Arte , Patologia , HumanosRESUMO
Immunotherapy has become a promising cancer treatment in the past decade, and IHC is the most commonly used testing method for PDL-1/PD1 evaluation. In general, PD-L1 assays can be performed on both FFPE specimens and cytological samples. However, their use on smears is not yet well-established or validated. Nowadays, digital images and advanced algorithms can aid in interpreting PD-L1 in cytological samples. Understanding the immune environment of non-small cell lung cancer (NSCLC) is critical in developing successful anticancer immunotherapies. The use of a multiplexed immunofluorescence (mIF) assay on cytological samples obtained through minimally invasive methods appears to be a viable option for investigating the immune environment of NSCLC. This review aims to briefly summarize the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Pulmão/patologia , Imunoterapia , Biomarcadores Tumorais/análiseRESUMO
OBJECTIVE: Immunocytochemistry (ICC) is essential for enhancing diagnostic accuracy and identifying markers for diagnosis, prognosis and targeted therapies. While cell blocks (CBs) are preferred for standardization and optimized staining, cytological smears are an alternative when CBs are unavailable. However, the literature on ICC protocols for smears is sparse. This review addresses preparation, fixation and protocols for nuclear and cytoplasmic antibodies on smears, drawing from our laboratory's experience. METHODS: We reviewed procedures for ICC on cytological smears using existing literature and practical insights from our laboratory. RESULTS: Commercially available antibodies were found to be reliable for ICC on smears if specimens are properly prepared and fixed. Protocols developed in our laboratory maintained antigenicity and provided clear staining results. CONCLUSIONS: Although ICC on CBs is the gold standard for standardization, cytological smears are a viable alternative when CBs are unavailable. Success in ICC on smears depends on proper preparation and fixation. This review offers practical protocols and insights to help laboratories optimize ICC on cytological smears. Further research and standardization are necessary to enhance reproducibility and reliability of ICC on smears. The practical information provided is based on personal experience in our laboratory.
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Technology-based education of children with special needs has become the focus of many research works in recent years. The wide range of different disabilities that are encompassed by the term "special needs", together with the educational requirements of the children affected, represent an enormous multidisciplinary challenge for the research community. In this article, we present a systematic literature review of technology-enhanced and game-based learning systems and methods applied on children with special needs. The article analyzes the state-of-the-art of the research in this field by selecting a group of primary studies and answering a set of research questions. Although there are some previous systematic reviews, it is still not clear what the best tools, games or academic subjects (with technology-enhanced, game-based learning) are, out of those that have obtained good results with children with special needs. The 18 articles selected (carefully filtered out of 614 contributions) have been used to reveal the most frequent disabilities, the different technologies used in the prototypes, the number of learning subjects, and the kind of learning games used. The article also summarizes research opportunities identified in the primary studies.
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Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models. Here, we investigated the presence of NETs in a variety of human solid tumours and their association with IL-8 (CXCL8) protein expression and CD8+ T-cell density in the tumour microenvironment. Multiplex immunofluorescence panels were developed to identify NETs in human cancer tissues by co-staining with the granulocyte marker CD15, the neutrophil marker myeloperoxidase and citrullinated histone H3 (H3Cit), as well as IL-8 protein and CD8+ T cells. Three ELISA methods to detect and quantify circulating NETs in serum were optimised and utilised. Whole tumour sections and tissue microarrays from patients with non-small cell lung cancer (NSCLC; n = 14), bladder cancer (n = 14), melanoma (n = 11), breast cancer (n = 31), colorectal cancer (n = 20) and mesothelioma (n = 61) were studied. Also, serum samples collected retrospectively from patients with metastatic melanoma (n = 12) and NSCLC (n = 34) were ELISA assayed to quantify circulating NETs and IL-8. NETs were detected in six different human cancer types with wide individual variation in terms of tissue density and distribution. At least in NSCLC, bladder cancer and metastatic melanoma, NET density positively correlated with IL-8 protein expression and inversely correlated with CD8+ T-cell densities. In a series of serum samples from melanoma and NSCLC patients, a positive correlation between circulating NETs and IL-8 was found. In conclusion, NETs are detectable in formalin-fixed human biopsy samples from solid tumours and in the circulation of cancer patients with a considerable degree of individual variation. NETs show a positive association with IL-8 and a trend towards a negative association with CD8+ tumour-infiltrating lymphocytes. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Linfócitos T CD8-Positivos/imunologia , Armadilhas Extracelulares/imunologia , Interleucina-8/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , HumanosRESUMO
OBJECTIVE: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. METHODS: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. RESULTS: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). CONCLUSIONS: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.
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Tireotoxicose , Autoanticorpos , Diagnóstico Diferencial , Humanos , Cintilografia , Receptores da Tireotropina/imunologia , Estudos Retrospectivos , Tireotoxicose/diagnóstico por imagem , Tireotoxicose/imunologiaRESUMO
OBJECTIVE: Understanding the immune environment of non-small cell lung cancer (NSCLC) is important for designing effective anticancer immunotherapies. We describe the use of multiplex immunofluorescence (mIF) assays to enable characterisation of the tumour-infiltrating immune cells and their interactions, both across and within immune subtypes. METHODS: Six cytological samples of NSCLC taken by transoesophageal ultrasound-guided fine needle aspiration were tested with an mIF assay designed to detect the expression of key immune cell markers such as CD3, CD8, CD20, CD11b, and CD68. Pan-cytokeratin was used to detect the NSCLC cells. Fluorescence images were acquired on a Vectra-Polaris Automated Quantitative Pathology Imaging System (Akoya Biosciences). RESULTS: MIF assay was able to reliably detect and quantify the myeloid cell markers CD11b, CD68, CD3+ and CD8+ T cells, and CD20+ B lymphocytes on cytological samples of NSCLC. Whole-tissue analysis and its correlation with the corresponding H&E stains allowed a better understanding of the tissue morphology and the relationship between tumour and stroma compartments. Additionally, a uniform, specific, and correct staining pattern was seen for every immune marker. CONCLUSION: The implementation of mIF assay on cytological samples taken with minimally invasive methods seems feasible and can be used to explore the immune environment of NSCLC.
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Biomarcadores/metabolismo , Imunofluorescência/métodos , Imunoensaio/métodos , Linfócitos B/metabolismo , Biópsia por Agulha Fina/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Técnicas Citológicas/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Células Mieloides/metabolismo , Coloração e Rotulagem/métodosRESUMO
The precise nature of the local immune responses in lung tuberculosis (TB) granulomas requires a comprehensive understanding of their environmental complexities. At its most basic level, a granuloma is a compact, organized immune aggregate of macrophages surrounded by myeloid, B and T cells. We established two complementary multiplex immunolabeling panels to simultaneously evaluate the myeloid and lymphocytic contexture of 14 human lung TB granulomas in formalin-fixed paraffin-embedded tissue samples. We observed diverse CD3+ and CD8+ T-cell and CD20+ B lymphocyte compositions of the granuloma immune environment and a relatively homogeneous distribution of all myeloid cells. We also found significant associations between CD8+ T-cell densities and the myeloid marker CD11b and phagocytic cell marker CD68. In addition, significantly more CD68+ macrophages and CD8+ T cells were found in Mycobacterium tuberculosis-infected granulomas, as detected by Ziehl-Neelsen staining. FOXP3 expression was predominately found in a small subset of CD4+ T cells in different granulomas. As the success or failure of each granuloma is determined by the immune response within that granuloma at a local and not a systemic level, we attempted to identify the presence of reactive T cells based on expression of the T-cell activation marker CD137 (4-1BB) and programmed cell death-1 (PD-1). Only a small fraction of the CD4+ and CD8+ T cells expressed PD-1. CD137 expression was found only in a very small fraction of the CD4+ T cells in two granulomas. Our results also showed that multinucleated giant cells showed strong PD-L1 but not CTLA-4 membrane staining. This study offers new insights into the heterogeneity of immune cell infiltration in lung TB granulomas, suggesting that each TB granuloma represents a unique immune environment that might be independently influenced by the local adaptive immune response, bacterial state, and overall host disease status.
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Imunidade Adaptativa , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Microambiente Celular/imunologia , Imunofluorescência , Granuloma/imunologia , Imunofenotipagem , Pulmão/imunologia , Mycobacterium tuberculosis/imunologia , Células Mieloides/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Idoso , Biomarcadores/análise , Granuloma/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/microbiologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Fenótipo , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Although substance use and violent behaviors often emerge together in adolescence, and both have similar widely cited causes and negative consequences for development, it remains unclear whether and how they may be linked causally. This study of early adolescents in Mexico's three largest cities tested whether alcohol use and violence perpetration are temporally related, whether their relationship is unidirectional or reciprocal, and whether the relationship differs by gender and the type of violence. The study employed longitudinal data from seventh grade students (N = 4830; M age = 12.0, range 11-15; 49% female) in 18 public middle schools in Mexico City, Guadalajara and Monterrey. Students completed questionnaires at the beginning, middle, and end of the 2014-2015 academic year. Students' responses to a multi-dimensional violence assessment emerged in two distinct patterns: criminally violent acts, and bullying/aggression. Although males engaged in both types of violence more frequently than females at all three time points, they used alcohol more frequently than females only at the first survey, after which the gender gap disappeared. Cross-lagged multi-group path models showed that, for both males and females, more frequent alcohol use predicted subsequent increases in criminally violent behavior, and bullying/aggression predicted later increases in alcohol use. Reciprocal associations varied by gender and type of violence: Alcohol use was reciprocally linked to criminally violent behavior among males only, and reciprocally linked to bullying-aggression among females alone. The results are interpreted in the context of sharply increasing rates of violence in Mexico and changing gender norms, with implications for youth prevention programs.
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Consumo de Bebidas Alcoólicas , Violência , Adolescente , Comportamento do Adolescente , Agressão , Bullying , Criança , Feminino , Humanos , Masculino , México , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários , Violência/estatística & dados numéricosRESUMO
BACKGROUND: The development of a more refined prognostic methodology for early non-small cell lung cancer (NSCLC) is an unmet clinical need. An accurate prognostic tool might help to select patients at early stages for adjuvant therapies. RESULTS: A new integrated bioinformatics searching strategy, that combines gene copy number alterations and expression, together with clinical parameters was applied to derive two prognostic genomic signatures. The proposed methodology combines data from patients with and without clinical data with a priori information on the ability of a gene to be a prognostic marker. Two initial candidate sets of 513 and 150 genes for lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively, were generated by identifying genes which have both: a) significant correlation between copy number and gene expression, and b) significant prognostic value at the gene expression level in external databases. From these candidates, two panels of 7 (ADC) and 5 (SCC) genes were further identified via semi-supervised learning. These panels, together with clinical data (stage, age and sex), were used to construct the ADC and SCC hazard scores combining clinical and genomic data. The signatures were validated in two independent datasets (n = 73 for ADC, n = 97 for SCC), confirming that the prognostic value of both clinical-genomic models is robust, statistically significant (P = 0.008 for ADC and P = 0.019 for SCC) and outperforms both the clinical models (P = 0.060 for ADC and P = 0.121 for SCC) and the genomic models applied separately (P = 0.350 for ADC and P = 0.269 for SCC). CONCLUSION: The present work provides a methodology to generate a robust signature using copy number data that can be potentially used to any cancer. Using it, we found new prognostic scores based on tumor DNA that, jointly with clinical information, are able to predict overall survival (OS) in patients with early-stage ADC and SCC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Dosagem de Genes/genética , Proteínas de Neoplasias/genética , Prognóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Genômica , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas de Neoplasias/biossíntese , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAF(V600E) (cfBRAF(V600E)). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAF(V600E) by ddPCR in patients with melanoma during therapy with BRAF inhibitors. METHODS: Plasma concentrations of cfBRAF(V600E) were measured in 8 controls and 20 patients with advanced melanoma having the BRAF(V600E) mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. RESULTS: The BRAF(V600E) mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAF(V600E) and plasma cfBRAF(V600E) was 84.3%. Baseline cfBRAF(V600E) correlated with tumor burden (r = 0.742, P < 0.001). cfBRAF(V600E) concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1-Q3, 27-647 copies/mL; first response median, 0 copies/mL; Q1-Q3, 0-49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1-Q3, 0-33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAF(V600E) compared with best response (median, 115 copies/mL; Q1-Q3, 3-707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAF(V600E) were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively). CONCLUSIONS: cfBRAF(V600E) quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.
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Análise Mutacional de DNA/métodos , DNA/sangue , Melanoma/tratamento farmacológico , Mutação , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , DNA/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Indóis/administração & dosagem , Indóis/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melanoma/sangue , Melanoma/genética , Melanoma/mortalidade , Pessoa de Meia-Idade , Oximas/administração & dosagem , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Resultado do Tratamento , VemurafenibRESUMO
In the 21st century, there has been a dramatic shift in the diagnosis and management of non-small cell lung carcinoma (NSCLC), with an increasing use of minimally invasive tissue acquisition methods. Current treatments require morphologic subtyping and biomarker information in all cases. Determining such biomarkers is a continuously evolving field; current guidelines state that the determination of mutations on the Epidermal Growth Factor (EFGR), Kirsten Rat Sarcoma viral oncogene homolog (KRAS), Proto-oncogene B-Raf (BRAF), Human epidermal growth factor receptor 2 (HER2) and Anaplastic Lymphoma Kinase (ALK), genes as well as fusions on genes such as ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1), MET proto-oncogene, receptor tyrosine kinase (MET), RET proto-oncogene (RET), and the Neurotrophic Tyrosine Receptor Kinase (NTRK) family is mandatory. While analyzing such alterations, some of them were first reported to be mutually exclusive, although in recent years, it has been shown otherwise in some of these cases. Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Proto-Oncogene Mas , Receptor trkA , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptor trkA/genética , Translocação Genética , IdosoRESUMO
BACKGROUND: Cytological samples play a critical role in diagnosing advanced-stage tumors and those arising in difficult-to-reach anatomical sites such as the pancreatobiliary tract, lung, thyroid, suprarenal, pelvis, and others such as salivary glands. These samples are often the only available material for accurate diagnosis and for performing ancillary studies, such as immunocytochemistry (ICC) or the detection of molecular biomarkers. SUMMARY: While the use of immunohistochemistry is well established and standardized on formalin-fixed-paraffin-embedded histological tissue, in cytological samples, it presents unique challenges. Methods used for obtaining and processing these specimens are complex and are not standardized among laboratories. Moreover, there is also diversity in the types of cytological samples potentially suitable for ICC. KEY MESSAGES: This review explores the current landscape of ICC practices in European and North American laboratories, highlighting variability in methods and the need for standardization to ensure reliable results and reproducibility of ICC on cytological specimens.
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INTRODUCTION: The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and prognostic potential across different tumor types. Spatially resolved tissue-based technologies allowed researchers to simultaneously quantify different immune populations in tumor samples. However, bare quantification fails to harness the spatial nature of tissue-based technologies. Tumor-immune interactions are associated with specific spatial patterns that can be measured. In recent years, several computational tools have been developed to increase our understanding of these spatial patterns. TOPICS COVERED: In this review, we cover standard techniques as well as new advances in the field of spatial analysis of the immune microenvironment. We focused on marker quantification, spatial intratumor heterogeneity analysis, cellâcell spatial interaction studies and neighborhood analyses.
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Neoplasias , Microambiente Tumoral , Microambiente Tumoral/imunologia , Humanos , Neoplasias/imunologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , AnimaisRESUMO
The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians.
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Neoplasias Pancreáticas , Organização Mundial da Saúde , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Citodiagnóstico/métodos , Citodiagnóstico/normas , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/diagnóstico , CitologiaRESUMO
The increasing comprehension of molecular mechanisms underlying lung cancer and the discovery of targetable genomic alterations has dramatically change the pathological approach to lung cancer, especially non-small cell lung cancer (NSCLC). This unstoppable knowledge has taken pathologists to the leading front on lung cancer management. This is especially relevant in the world of cytopathology where "doing more with less" is a daily challenge. Nowadays with a growing number of predictive biomarkers needed to manage patients with NSCLC, there has been a paradigm shift in care and handling of diagnostic samples. One of the main emphasis and interest relies on the utilization of cytologic samples and small biopsies for not only diagnostic purposes but also for ancillary testing. Moreover, lung cytopathology is in continuous evolutions with implementation of new diagnostic techniques, new tools, and facing new challenges. The goal of this paper will be to provide the reader with the necessary concepts than can be used to exploit the cytological samples in order to use these samples for comprehensive diagnosis and relevant ancillary testing purposes.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , PulmãoRESUMO
Multiplexed immunofluorescence imaging of formalin-fixed, paraffin-embedded (FFPE) specimens mounted on glass slides allow the identification of multiple cell phenotypes while retaining spatial and morphological context. Multiplex immunofluorescence protocols have already been developed and validated for mouse tissues. Immunophenotyping analysis reliably depicts the immune landscape of cancer tissues that has been demonstrated to influence cancer development and progression as well as to have an impact on therapy responsiveness and resistance. Here, we describe a method for multiplexed fluorescence image analysis, enabling analysis of mouse cancer morphology and cell phenotypes in FFPE sections.
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Neoplasias , Animais , Camundongos , Imunofluorescência , Inclusão em Parafina , Fixação de Tecidos/métodos , FormaldeídoRESUMO
Non-small cell lung cancer (NSCLC) is one of the oncological entities with the greatest evolution in molecular diagnosis due to the large number of diagnostic biomarkers and new treatments approved by international regulatory agencies. An accurate, early diagnosis using the least amount of tissue is the goal for the establishing and developing precision medicine for these patients. Rapid on-site evaluation (ROSE) provides cytological samples of optimal quantity and quality for a complete diagnosis of NSCLC. The usefulness of cytological samples has been demonstrated, not only for massive parallel sequencing but also for the quantification of the expression of programmed death-ligand 1 (PD-L1) and tumour mutational burden (TMB). Pre-analytical, analytical, and post-analytical recommendations are made for the management and appropriate use of cytological samples in order to obtain all the information necessary for the diagnosis and treatment of patients with NSCLC according to current quality parameters.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Imuno-Histoquímica , CitodiagnósticoRESUMO
Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology and the Spanish Society of Medical Oncology have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.