RESUMEN
Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Organización Mundial de la Salud , Humanos , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/clasificación , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirugía , Lesiones Precancerosas/patología , Lesiones Precancerosas/clasificación , PronósticoRESUMEN
AIMS: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.
Asunto(s)
Biopsia/clasificación , Diferenciación Celular , Células de Paneth/patología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Anciano , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , Lesiones Precancerosas/clasificación , Estudios Retrospectivos , Neoplasias Gástricas/clasificación , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND AND AIM: Recently, the BLI Adenoma Serrated International Classification (BASIC) system was developed by European experts to differentiate colorectal polyps. Our aim was to validate the BASIC classification system among the US-based endoscopy experts. METHODS: Participants utilized a web-based interactive learning system where the group was asked to characterize polyps using the BASIC criteria: polyp surface (presence of mucus, regular/irregular and [pseudo]depressed), pit appearance (featureless, round/non-round with/without dark spots; homogeneous/heterogeneous distribution with/without focal loss), and vessels (present/absent, lacy, peri-cryptal, irregular). The final testing consisted of reviewing BLI images/videos to determine whether the criteria accurately predicted the histology results. Confidence in adenoma identification (rated "1" to "5") and agreement in polyp (adenoma vs non-adenoma) identification and characterization per BASIC criteria were derived. Strength of interobserver agreement with kappa (k) value was reported for adenoma identification. RESULTS: Ten endoscopy experts from the United States identified conventional adenoma (vs non-adenoma) with 94.4% accuracy, 95.0% sensitivity, 93.8% specificity, 93.8% positive predictive value, and 94.9% negative predictive value using BASIC criteria. Overall strength of interobserver agreement was high: kappa 0.89 (0.82-0.96). Agreement for the individual criteria was as follows: surface mucus (93.8%), regularity (65.6%), type of pit (40.6%), pit visibility (66.9%), pit distribution (57%), vessel visibility (73%), and being lacy (46%) and peri-cryptal (61%). The confidence in diagnosis was rated at high ≥4 in 67% of the cases. CONCLUSIONS: A group of US-based endoscopy experts have validated a simple and easily reproducible BLI classification system to characterize colorectal polyps with >90% accuracy and a high level of interobserver agreement.
Asunto(s)
Adenoma , Pólipos del Colon , Colonoscopía , Neoplasias Colorrectales , Imagen Óptica , Lesiones Precancerosas , Adenoma/clasificación , Adenoma/diagnóstico por imagen , Adenoma/patología , Pólipos Adenomatosos/clasificación , Pólipos Adenomatosos/diagnóstico por imagen , Pólipos Adenomatosos/patología , Pólipos del Colon/clasificación , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Colonoscopía/normas , Color , Neoplasias Colorrectales/diagnóstico por imagen , Humanos , Luz , Variaciones Dependientes del Observador , Imagen Óptica/normas , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Sensibilidad y Especificidad , Estados UnidosRESUMEN
Objetivo: Los desórdenes de mucosa bucal potencialmente malignos pueden presentar áreas displásicas. En estos casos, la biopsia es un procedimiento imprescindible para un correcto diagnóstico. La inspección visual y la palpación, como método de selección del área de biopsia, ofrecen sensibilidad y especificidad adecuadas pero mejorables. El objetivo de este artículo es presentar una serie de casos clínicos en los que se describen el empleo y la interpretación de la tinción vital con azul de toluidina como método complementario para contribuir a una mejor elección del área de biopsia. Casos clínicos: Se trata de siete casos de lesiones con sospecha de displasia epitelial en mucosa bucal. En cada uno se detalla la correlación de las áreas teñidas con las manifestaciones clínicas y con el diagnóstico de displasia. Además, se muestran patrones de tinción considerados falsos positivos. En la interpretación de la tinción positiva, se tuvieron en cuenta el aspecto superficial y el color de la lesión teñida. El empleo combinado de inspección, palpación y tinción vital podría constituir un procedimiento integral de utilidad para obtener mayor precisión en la determinación del sitio de biopsia en comparación con los mismos procedimientos aplicados de manera individual. En la interpretación de la tinción positiva con azul de toluidina deberían considerarse el aspecto superficial y el color de la lesión teñida (AU)
Aim: Potentially Malignant Disorders in the oral cavity can present dysplastic areas. In these cases, the biopsy is an essential procedure for a correct diagnosis. Visual inspection and palpation, are adequate methods to select the area for the biopsy, however there is margin for improvement. The objective of this article is to present a series of clinical cases in which the use and interpretation of vital staining with Toluidine Blue is described as a complementary method to contribute to a better choice of the biopsy area. Clinical cases: Seven clinical cases that presented lesions with suspected epithelial dysplasia in the oral mucosa were presented. The correlation of the stained areas with the clinical manifestations and with the diagnosis of dysplasia is detailed in each case. Staining patterns considered false positives are also shown. In the interpretation of the positive staining, the superficial appearance and color of the stained lesion were considered. The combined use of inspection, palpation and vital staining could constitute a useful comprehensive procedure to obtain greater precision in determining the biopsy site in relation to the same procedures applied individually. In the interpretation of the positive staining with Toluidine Blue, the superficial appearance and color of the stained lesion should be considered (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Lesiones Precancerosas/clasificación , Cloruro de Tolonio , Detección Precoz del Cáncer/métodos , Mucosa Bucal/lesiones , Palpación , Biopsia/métodos , Neoplasias de los Labios/diagnóstico , Diagnóstico Clínico , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnósticoRESUMEN
BACKGROUND: Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated lesions (SSL), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as "serrated." Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult. METHODS: We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies. RESULTS: SSLs could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSLs. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion. CONCLUSIONS: Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.
Asunto(s)
Adenoma/clasificación , Pólipos Adenomatosos/clasificación , Neoplasias Colorrectales/clasificación , Lesiones Precancerosas/clasificación , Adenoma/patología , Pólipos Adenomatosos/patología , Biomarcadores/análisis , Colon/patología , Neoplasias Colorrectales/patología , Femenino , Humanos , Hibridación in Situ , Masculino , Lesiones Precancerosas/patología , ARN Mensajero/análisis , Recto/patologíaRESUMEN
Contemporary catalogues of cancer driver genes rely primarily on high mutation rates as evidence for gene selection in tumors. Here, we present The Functional Alteration Bias Recovery In Coding-regions Cancer Portal, a comprehensive catalogue of gene selection in cancer based purely on the biochemical functional effects of mutations at the protein level. Gene selection in the portal is quantified by combining genomics data with rich proteomic annotations. Genes are ranked according to the strength of evidence for selection in tumor, based on rigorous and robust statistics. The portal covers the entire human coding genome (â¼18,000 protein-coding genes) across 33 cancer types and pan-cancer. It includes a selected set of cross-references to the most relevant resources providing genomics, proteomics, and cancer-related information. We showcase the portal with known and overlooked cancer genes, demonstrating the utility of the portal via its simple visual interface, which allows users to pivot between gene-centric and cancer type views. The portal is available at fabric-cancer.huji.ac.il. SIGNIFICANCE: A new cancer portal quantifies and presents gene selection in tumor over the entire human coding genome across 33 cancer types and pan-cancer.
Asunto(s)
Bases de Datos Genéticas , Genómica/métodos , Neoplasias/genética , Oncogenes/genética , Sistemas de Lectura Abierta/genética , Algoritmos , Femenino , Genoma Humano/genética , Humanos , Internet , Masculino , Tasa de Mutación , Neoplasias/clasificación , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/genética , Selección Genética , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.
Asunto(s)
Carcinoma in Situ , Clasificación/métodos , Enfermedades de la Laringe , Neoplasias Laríngeas , Lesiones Precancerosas/clasificación , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Historia , Humanos , Enfermedades de la Laringe/diagnóstico , Enfermedades de la Laringe/patología , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patologíaRESUMEN
BACKGROUND: In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks. METHODS: From a total of 1233 patients undergoing thyroid FNAs between 2010 and 2014 at the University of Washington, 119 had AUS/FLUS without nuclear atypia, and 64 with nuclear atypia. Outcomes for patients with and without nuclear atypia (with the exception of 24 patients lost to follow-up) were evaluated and results were compared. RESULTS: 16/57 (28.1%) patients with AUS/FLUS and nuclear atypia subsequently had carcinomas on thyroidectomy, statistically higher than the 8/102 patients (7.8%, P = .001) without nuclear atypia. When comparing only patients who underwent surgery (n = 63), again those with AUS/FLUS and nuclear atypia had statistically higher rates of carcinoma (16/31, 51.6%), compared to those without (8/32, 25%; P = .0394). Overall, 24/159 (15.1%) of patients with AUS/FLUS had carcinoma on subsequent histology. CONCLUSION: Malignancy rates for AUS/FLUS were in line with TBS estimated risks. However, our data demonstrate that the presence or absence of nuclear atypia is associated with different malignancy rates, suggesting the possibility that the AUS/FLUS category may best be split into two subcategories with different implied risks of malignancy.
Asunto(s)
Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/patología , Biopsia con Aguja Fina , Femenino , Humanos , Masculino , Lesiones Precancerosas/diagnóstico , Neoplasias de la Tiroides/diagnósticoRESUMEN
BACKGROUND AND AIMS: Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up. MATERIALS AND METHODS: Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms. RESULTS: The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases. CONCLUSION: Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.
Asunto(s)
Neoplasias Intraductales Pancreáticas/terapia , Neoplasias Pancreáticas/terapia , Lesiones Precancerosas/terapia , Cuidados Posteriores , Humanos , Neoplasias Intraductales Pancreáticas/clasificación , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/cirugía , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/cirugíaRESUMEN
Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200 µm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC from ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared with luminal A and HER2 subtypes. DCIS and IBC were distinguished on the basis of cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, and PS (38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer, with potential implications for breast cancer pathogenesis. SIGNIFICANCE: These findings present the first in situ metabolomic findings of the four molecular subtypes of breast cancer, DCIS, and normal tissue, and add to the understanding of their pathogenesis.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Lípidos/análisis , Lesiones Precancerosas/patología , Biomarcadores de Tumor/metabolismo , Mama/patología , Neoplasias de la Mama/clasificación , Carcinoma Ductal de Mama/clasificación , Carcinoma Intraductal no Infiltrante/clasificación , Progresión de la Enfermedad , Femenino , Humanos , Metabolismo de los Lípidos , Lipidómica/métodos , Lesiones Precancerosas/clasificación , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Basaloid salivary gland neoplasms (BSNs), which include benign primary tumors and primary or metastatic malignancies, show overlapping morphology in fine-needle aspiration (FNA). The Milan system recommends assigning a grade (low or high) to malignant salivary neoplasms because of the impact on surgical planning. This study investigated cytomorphologic features of BSNs on FNA that would help to favor a high-grade malignancy over a low-grade malignancy or a benign tumor. METHODS: Two pathologists performed a double-blinded cytologic evaluation of FNA cases diagnosed as BSNs that had corresponding surgical resections. The diagnosis made with the Milan system was correlated with the final surgical diagnosis and grade. Cytologic sensitivity, specificity, and predictive values were calculated. RESULTS: There were 132 BSN FNA cases; cytology slides were available for 77 of 87 patients who had undergone resection. The risk of malignancy for the benign neoplasm (BN), salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SFM), and malignant categories were 13.6%, 22%, 100%, and 100%, respectively. The sensitivity of the malignant/SFM category was 51.7%; another 37.9% of confirmed malignancies were diagnosed as SUMP. The specificity of the BN category was 86%. Favoring a high-grade malignancy on FNA had 100% accuracy (5 of 5). Favoring a low-grade malignancy on FNA had 75% accuracy (6 of 8). The most specific cytomorphologic clues for a high-grade malignancy were necrotic/apoptotic debris, mitoses, discohesion, and anisonucleosis. CONCLUSIONS: BSNs encompass a broad spectrum of primary and metastatic tumors. Necrotic/apoptotic debris, mitotic activity, discohesion, and significant anisonucleosis, alone or especially in combination, should make a cytopathologist suspect a high-grade malignancy.
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Lesiones Precancerosas/diagnóstico , Neoplasias de las Glándulas Salivales/diagnóstico , Glándulas Salivales/patología , Biopsia con Aguja Fina , Toma de Decisiones Clínicas/métodos , Humanos , Clasificación del Tumor , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía , Estudios Retrospectivos , Medición de Riesgo/métodos , Neoplasias de las Glándulas Salivales/clasificación , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/cirugía , Glándulas Salivales/cirugíaRESUMEN
BACKGROUND: The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance. METHODS: We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery. RESULTS: The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies. CONCLUSIONS: Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.
Asunto(s)
Páncreas/cirugía , Quiste Pancreático/cirugía , Neoplasias Pancreáticas/cirugía , Lesiones Precancerosas/cirugía , Humanos , Páncreas/patología , Pancreatectomía , Quiste Pancreático/clasificación , Quiste Pancreático/diagnóstico , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/diagnóstico , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/diagnósticoRESUMEN
Benign normal (NL), premalignant (endometrial intraepithelial neoplasia, EIN) and malignant (cancer, EMCA) endometria must be precisely distinguished for optimal management. EIN was objectively defined previously as a regression model incorporating manually traced histologic variables to predict clonal growth and cancer outcomes. Results from this early computational study were used to revise subjective endometrial precancer diagnostic criteria currently in use. We here use automated feature segmentation and updated machine learning algorithms to develop a new classification algorithm. Endometrial tissue from 148 patients was randomly separated into 72-patient training and 76-patient validation cohorts encompassing all 3 diagnostic classes. We applied image analysis software to keratin stained endometrial tissues to automatically segment whole-slide digital images into epithelium, cells, and nuclei and extract corresponding variables. A total of 1413 variables were culled to 75 based on random forest classification performance in a 3-group (NL, EIN, EMCA) model. This algorithm correctly classifies cases with 3-class error rates of 0.04 (training set) and 0.058 (validation set); and 2-class (NL vs. EIN+EMCA) error rate of 0.016 (training set) and 0 (validation set). The 4 most heavily weighted variables are surrogates of those previously identified in manual-segmentation machine learning studies (stromal and epithelial area percentages, and normalized epithelial surface lengths). Lesser weighted predictors include gland and lumen axis lengths and ratios, and individual cell measures. Automated image analysis and random forest classification algorithms can classify normal, premalignant, and malignant endometrial tissues. Highest predictive variables overlap with those discovered independently in early models based on manual segmentation.
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Algoritmos , Hiperplasia Endometrial/clasificación , Neoplasias Endometriales/clasificación , Aprendizaje Automático , Lesiones Precancerosas/clasificación , Estudios de Cohortes , Hiperplasia Endometrial/patología , Neoplasias Endometriales/patología , Endometrio/patología , Células Epiteliales/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Estadísticos , Lesiones Precancerosas/patología , Flujo de TrabajoRESUMEN
Serrated polyps evaluation represents a challenge for pathologists for lacking of univocal criteria that leads to different inter -individual interpretation. The aim of our review is to offer an alternative simpler histologic and endoscopic approach to these lesions for a more correct relationship between endoscopists and pathologists.
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Pólipos del Colon/clasificación , Pólipos del Colon/patología , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , HumanosRESUMEN
We propose an approach for characterizing structural heterogeneity of lung cancer nodules using Computed Tomography Texture Analysis (CTTA). Measures of heterogeneity were used to test the hypothesis that heterogeneity can be used as predictor of nodule malignancy and patient survival. To do this, we use the National Lung Screening Trial (NLST) dataset to determine if heterogeneity can represent differences between nodules in lung cancer and nodules in non-lung cancer patients. 253 participants are in the training set and 207 participants in the test set. To discriminate cancerous from non-cancerous nodules at the time of diagnosis, a combination of heterogeneity and radiomic features were evaluated to produce the best area under receiver operating characteristic curve (AUROC) of 0.85 and accuracy 81.64%. Second, we tested the hypothesis that heterogeneity can predict patient survival. We analyzed 40 patients diagnosed with lung adenocarcinoma (20 short-term and 20 long-term survival patients) using a leave-one-out cross validation approach for performance evaluation. A combination of heterogeneity features and radiomic features produce an AUROC of 0.9 and an accuracy of 85% to discriminate long- and short-term survivors.
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Adenocarcinoma del Pulmón/clasificación , Neoplasias Pulmonares/clasificación , Lesiones Precancerosas/clasificación , Radiografía/métodos , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma del Pulmón/diagnóstico por imagen , Anciano , Área Bajo la Curva , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico por imagen , Curva ROC , Especificidad de la Especie , Análisis de SupervivenciaRESUMEN
AIMS: To evaluate OPN, MCM7, Ki-67, p53, Bcl-2 and 53BP1 presence, together with the abnormal adaptive CD4 and CD8 T-cell response markers expression in a series of oral lichen planus (OLP) affected patients and assess their combined contribution for a more objective disease classification. METHODS AND RESULTS: In this ex-vivo retrospective analysis, biopsy specimens from 28 adults with a clinical diagnosis of OLP at different progression degree (16 reticular, 2 plaque-like, 1 erosive and 9 mixed type) were collected. Sections were immunohistochemically investigated for the proinflammatory cytokine osteopontin (OPN), alpha-beta CD4 and CD8 positive T cells, DNA replication licensing factor (MCM7), proliferating cell marker (Ki-67), apoptotic and tumor antigen (p53), apoptosis modulator (Bcl-2) and cellular response regulator to double-strand breaks tumor suppressor p53-binding protein 1 expression. Statistical analysis revealed that 53BP1 is highly represented among the OLP study patients (p<0.05). Moreover, on the basis of the quantification results of the highly expressed parameters, two illness categories with different severity were evidenced. The classification hypothesis was confirmed by i) OLP lesion persistence, ii) the development of oral severe lesions in the patients belonging to high grade activity OLP group (HGA-OLPs) and iii) the ascertainment of the same evidence both in the oral squamous cell tumor controls (OSCC) and in HGA-OLP cases. CONCLUSION: This study completes the scenario with respect to early detection, thanks to a more precise histological analysis, for rationalizing the clinical and histological findings toward a sharable international disease scoring system.
Asunto(s)
Transformación Celular Neoplásica , Liquen Plano Oral/clasificación , Liquen Plano Oral/patología , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non-atypical EH. A systematic review and meta-analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non-atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p-value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non-atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non-atypical EH. Complex non-atypical EH may be regarded as a low-risk premalignant lesion rather than a benign condition.
Asunto(s)
Hiperplasia Endometrial/clasificación , Sesgo , Hiperplasia Endometrial/patología , Hiperplasia Endometrial/terapia , Neoplasias Endometriales/clasificación , Femenino , Humanos , Lesiones Precancerosas/clasificación , Organización Mundial de la SaludRESUMEN
Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.
Asunto(s)
Carcinoma de Células Escamosas/clasificación , Lesiones Precancerosas/clasificación , Neoplasias de la Vulva/clasificación , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma in Situ/virología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Progresión de la Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/virología , Neoplasias de la Vulva/genética , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/virologíaRESUMEN
Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms with poor outcomes. At the time of diagnosis, the disease is usually at an advanced stage and only a minority is eligible for surgical resection. To improve the prognosis, it is essential to diagnose and treat the disease in an early stage before its progression into an invasive disease. This article reviews clinical features, histopathology, cytopathology, and molecular alterations of pancreatic ductal adenocarcinoma and its precursors. Moreover, we review a recently updated two-tier classification system for precursor lesions, new findings in premalignant cystic neoplasms, and recently updated staging criteria for invasive carcinoma based on the Cancer Staging Manual, eighth edition, from the American Joint Committee on Cancer. Finally, we discuss the potential clinical applications of the rapidly growing molecular and genetic information of pancreatic cancer and its precursors.