RESUMEN
The study evaluated morphologic patterns, mutational profiles, and ß-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for ß-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n=90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. ß-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P=0.02). Mucinous differentiation (MD) was associated with KRAS mutations (P<0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ=0.82), whereas agreement on MD was weak (κ=0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with the presence of CTNNB1 mutations (P<0.01). CNL EAs demonstrate several morphologies with divergent molecular profiles. SD was significantly associated with CTNNB1 mutations and nuclear localization of ß-catenin in these tumors. Nuclear expression of ß-catenin is a sensitive and specific IHC marker for CTNNB1 mutations in CNL EAs. CNL EAs with KRAS mutations often displayed MD.
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Adenocarcinoma , Neoplasias Endometriales , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Análisis Mutacional de ADN , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Femenino , Humanos , Inmunohistoquímica , Mutación , beta Catenina/genéticaRESUMEN
Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.
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Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genómica , Animales , Manejo de la Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/terapia , Femenino , Estudios de Asociación Genética/métodos , Genómica/métodos , Humanos , Estadificación de Neoplasias , Pronóstico , Biopsia del Ganglio Linfático CentinelaRESUMEN
OBJECTIVES: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. RESULTS: Thirty-one angiogenic-related genes were significantly associated with survival (q≤0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p=0.01, HR=0.8), CD44 (q=0.003; TCGA p=0.05, HR=0.9), EPHB2 (q=0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q=0.02; TCGA p=0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q=0.03; GSE26712 p=0.01, HR=3.1); PF4 (q=0.02; GSE26712 p=0.01, HR=3.0); NRP1 (q=0.02; GSE26712 p<0.04, HR>1.4); COL4A3 (q=0.04; GSE26712 p=0.03, HR=1.3); and ANGPTL3 (q=0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. CONCLUSIONS: Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases.
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Cistadenocarcinoma Seroso/irrigación sanguínea , Cistadenocarcinoma Seroso/genética , Neoplasias Ováricas/irrigación sanguínea , Neoplasias Ováricas/genética , Adulto , Anciano , Antígenos CD/análisis , Biomarcadores de Tumor/genética , Cistadenocarcinoma Seroso/patología , Endoglina , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Clasificación del Tumor , Neovascularización Patológica/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Pronóstico , Modelos de Riesgos Proporcionales , Receptores de Superficie Celular/análisis , Tasa de SupervivenciaAsunto(s)
Neoplasias Abdominales , Disección/métodos , Enfermedades Fetales , Teratoma , Neoplasias Abdominales/diagnóstico por imagen , Neoplasias Abdominales/patología , Neoplasias Abdominales/cirugía , Adulto , Diagnóstico Diferencial , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/patología , Enfermedades Fetales/cirugía , Humanos , Recién Nacido , Masculino , Embarazo , Teratoma/diagnóstico , Teratoma/patología , Teratoma/cirugía , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Ultrasonografía Prenatal/métodosRESUMEN
Although only a small proportion of invasive squamous carcinoma of the cervix present with microinvasive disease, consistent recognition of this entity is important because it carries important management implications. The objective of this review was to reassess the methods and criteria for a histopathologic diagnosis of both early invasive squamous and adenocarcinomas in light of recent pathologic and clinicopathologic studies. The diagnosis of microinvasion is primarily histopathologic. Although the concept of microinvasion initially seems obvious, there are problems in diagnostic precision. A clear understanding of both the Society of Gynaecologic Oncologists' and the International Federation of Obstetricians and Gynecologists' classifications of early invasive disease is required. Subsequently, key parameters must be assessed-measurement of depth and lateral spread, assessment of margins, and identification of lymphovascular invasion-using accepted reference points and definitions. This assessment requires properly oriented and stained histologic sections of a loop electrosurgical excision procedure or cone specimen. Immunohistochemical staining of vascular endothelium or epithelial basement membrane has only a limited/adjunctive role. Controversy continues regarding the need to appraise the extent of any lymphovascular invasion and measurement in cases with multifocal invasion. Application of criteria to invasive adenocarcinomas seems warranted but is particularly challenging because of its special morphology and different biology.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Invasividad Neoplásica/patología , Estadificación de Neoplasias/métodos , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Femenino , Humanos , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Invasividad Neoplásica/diagnóstico , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. Electronic medical records were reviewed for clinical history, imaging findings, laboratory results, and follow-up. Pathology slides, immunohistochemistry, and ancillary studies were reviewed. There were two females and two males with age ranging from 52 to 74 years. There was one amphicrine carcinoma with tumor cells simultaneously demonstrating both hepatocellular and neuroendocrine differentiation, one mixed hepatocellular-neuroendocrine carcinoma (NEC) with hepatocellular component intermingled with neuroendocrine component, one small cell NEC, and one well-differentiated neuroendocrine tumor. Next- generation sequencing of the mixed hepatocellular-NEC and small cell NEC showed molecular/genetic alterations commonly seen in hepatocellular carcinoma (HCC). All four cases arose in a background of cirrhosis. Primary hepatic neoplasms arising in cirrhotic livers can have a spectrum of neuroendocrine differentiation. Presence of a NEC component may be an indicator of aggressiveness. In addition, primary hepatic carcinomas with neuroendocrine differentiation likely share the same molecular pathways as HCC.
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Carcinoma Hepatocelular/patología , Carcinoma Neuroendocrino/patología , Neoplasias Hepáticas/patología , Tumor Mixto Maligno/patología , Anciano , Carcinoma Hepatocelular/etiología , Carcinoma Neuroendocrino/etiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Tumor Mixto Maligno/etiologíaRESUMEN
BACKGROUND: Pelvic washings for patients with endometrial cancer is recommended but not used for staging. The International System for Reporting Serous Fluid Cytology (TIS) has standardized diagnostic categories, but the criteria remain incomplete. The 3 primary goals of this study were to 1) investigate features that distinguish atypical/indeterminate from malignant specimens, 2) measure the level of agreement between chart and reviewer diagnoses, and 3) determine whether the number of years in practice had an effect on the diagnoses rendered. METHODS: Pelvic washings and surgical pathology specimens for 52 patients with a chart diagnosis of atypical/indeterminate, suspicious, or malignant cytology and 52 age-matched controls with a negative chart diagnosis were included, reviewed blindly by 2 cytopathologists, and assigned a study diagnosis. Morphologic features were assessed. Agreement between original chart diagnoses and reviewer diagnoses were assessed as well as effect of years in practice. RESULTS: The overall cellularity in cell block (CB) slides for the malignant category was significantly increased compared with the atypical/indeterminate category (P < .0001). In addition, the number of atypical groups in ThinPrep for malignant washings was significantly increased compared with the atypical category (P < .001) and the negative and suspicious categories (P < .0001) in the CB. Overall agreement between the original and adjudicated diagnoses was high (γ = 0.983). There was no significant difference between diagnoses rendered and years in practice. CONCLUSION: The overall cellularity and number of atypical cells can be used to distinguish between malignant and atypical pelvic washing specimens. There is high reproducibility in the diagnostic categories and high agreement among pathologists, regardless of practice experience. These findings can help refine the criteria for TIS.
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Citodiagnóstico , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , Patólogos , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
In a series of 177 breast carcinomas, we found that the Oncotype DX Recurrence Score (RS) was correlated with six pathobiologic features: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status, and the three components of the Nottingham tumor grade. The RS also correlated with a composite index (the Breast Cancer Prognostic Score or BCPS) comprising the same six parameters. Categorical concordance was 56% and 66% using conventional and TAILORx cutoffs, respectively. Our data show that a composite prognostic index can be constructed from routinely reported breast tumor features that captures much of the information provided by the Oncotype assay at no added cost.
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Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Modelos Logísticos , Análisis Multivariante , Recurrencia Local de Neoplasia , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The objective of this study was to examine the clinicopathologic correlates of T-regulatory (T(reg)) cell infiltration in serous ovarian cancers and to define gene signatures associated with high T(reg)s. METHODS: Tumor infiltrating T(reg) and cytotoxic T-cells (CTLs) were quantitated in 232 primary serous ovarian cancers by immunostaining for FOXP3 and CD8. Expression microarray analysis was performed in a subset of 48 advanced cancers with the highest and lowest numbers of infiltrating T(reg)s and a genomic signature was developed using binary regression. ANOVA analysis was performed to assess the most differentially expressed genes and these genes were further assessed using Ingenuity Pathway Analysis (IPA) software. RESULTS: High T(reg) infiltration in ovarian cancers was associated with high grade (p<0.0001), advanced stage (p=0.004) and suboptimal debulking (p<0.04), but not with survival. In contrast, high tumor infiltrating CD8 CTL infiltration was associated with favorable survival (median survival 48.7 vs. 34.6 months, p=0.01). A microarray-based genomic signature for high tumor-infiltrating T(reg) cells had a 77% predictive accuracy using leave-one-out cross-validation. ANOVA of microarray data revealed the antigen presentation pathway as the most differentially expressed canonical pathway (p<0.00001) between cancers with high and low T(reg) cells. CONCLUSIONS: These data suggest that there may be an association between increased T(reg) cell infiltration in ovarian cancers and advanced stage. Increased T(reg) infiltration is characterized by a genomic signature enriched with several immunologic pathway genes. Therapeutic strategies that reduce tumor infiltrating T(reg) cells are under investigation and may prove useful in ovarian cancers with high numbers of these cells.
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Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Presentación de Antígeno , Femenino , Expresión Génica/inmunología , Humanos , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Ováricas/genética , Fenotipo , Linfocitos T Reguladores/patología , Adulto JovenRESUMEN
Many theories have been proffered to explain the histogenesis of endometriosis (Robboy et al., 2009). Generally, they divide into those that favour transplantation of endometrial fragments to ectopic sites, metaplasia of the multipotential celomic peritoneum and induction of undifferentiated mesenchyme in ectopic sites to form endometriotic tissues after exposure to substances released from shed endometrium.
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Endometriosis/etiología , Endometriosis/embriología , Endometriosis/fisiopatología , Endometrio/patología , Femenino , HumanosRESUMEN
The natural history of 27 cases of biologically malignant struma ovarii from a series of 88 cases of histologically malignant or histologically proliferative struma ovarii is described. The extraovarian spread was evident at presentation in 17 patients. The malignant nature of the other 10 tumors became apparent only after they recurred. The tumors measured 5 to 24.5 cm and were more than 50% thyroid tissue in all but 2 cases. The microscopic diagnosis of the thyroid tissue was follicular adenoma in 17 cases (63%), papillary carcinoma in 7 (26%), unremarkable in 2 (7%), and follicular carcinoma in 1 case (4%). Generally, the clinical course was protracted, with long-term survival documented in most patients. Clinical features predictive of biologic malignancy were the presence of adhesions, peritoneal fluid (> or = 1 L), or a serosal rent in the struma ovarii (including cystectomy). In addition, pathologic factors predictive of a poorer prognosis were large size (> or = 10 cm), strumal component more than 80%, and extensive papillary carcinoma, especially with solid areas, necrosis, and > or = 5 mitoses per 10 high-power fields. Follow-up for all patients was 1.5 to 33 years (mean=13.5 yr). On last follow-up 3 patients (11%) had no evidence of disease, 9 (33%) were alive with disease, 5 (19%) died of other causes, and 10 patients (37%) died of the disease. Death from disease occurred 1.5 to 32 years after diagnosis (mean=14 yr). Recurrence was seen as early as 2 months and as late as 29 years after initial surgery (mean=7 yr). Long-term follow-up is indicated in patients with any of the above-mentioned adverse indicators.
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Adenocarcinoma Folicular/patología , Neoplasias Ováricas/patología , Estruma Ovárico/patología , Adenocarcinoma Folicular/cirugía , Adolescente , Adulto , Niño , Femenino , Histocitoquímica , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/cirugía , Estruma Ovárico/cirugía , Adulto JovenRESUMEN
The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.
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Enfermedad de Paget Extramamaria/patología , Neoplasias de la Vulva/patología , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Enfermedad de Paget Extramamaria/metabolismo , Enfermedad de Paget Extramamaria/cirugía , Pronóstico , Factores de Riesgo , Neoplasias de la Vulva/metabolismo , Neoplasias de la Vulva/cirugíaRESUMEN
OBJECTIVES: We describe the cytological distribution of disease, correlate cytological diagnoses with human papillomavirus (HPV) DNA status and surgical biopsy diagnoses, determine if CD4 counts correlate with lesion severity, and compare anal-rectal data of HIV-infected patients (primarily men) with cervical data. MATERIALS AND METHODS: A retrospective search of the computerized database identified 118 HIV-positive patients who had anal-rectal cytology. Cytology results were compared with available follow-up data including repeat anal-rectal cytology tests, surgical biopsy, CD4 counts, and HPV DNA polymerase chain reaction-based genotyping. RESULTS: Cytological diagnoses included 3% unsatisfactory for diagnosis, 41% negative for intraepithelial lesion or malignancy (NILM), 23% atypical squamous cells of undermined significance (ASC-US), 31% low-grade squamous intraepithelial lesion (LSIL), and 2% high-grade squamous intraepithelial lesion (HSIL) (ASC-US/squamous intraepithelial lesion, 0.7:1). Two anal intraepithelial neoplasia (AIN) II, 10 AIN III, and 1 invasive squamous cell carcinoma were histologically detected (11%). The majority of AIN II was preceded by LSIL, 54%; ASC-US, 15%; and HSIL, 8%. The false-negative fraction was 23%. Sensitivity, specificity, negative predictive value, and positive predictive value were 92%, 8%, 33%, and 67%, respectively. Of those HPV tested concurrent with the first cytology specimen, 48% NILM, 78% ASC-US, and 100% LSIL were HPV positive. Mean CD4 counts (per microliter) were lower in patients with HSIL (243 [SD, 65]) compared with LSIL (400 [SD, 261]) and NILM (428 [SD, 232]). CONCLUSIONS: Anal-rectal cytology is a useful screening test. A high percentage of AIN II lesions were detected in this at-risk population, and the majority was detected following cytological abnormality.
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Canal Anal/patología , Infecciones por VIH/complicaciones , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Neoplasias del Recto/epidemiología , Recto/patología , Adulto , Anciano , Canal Anal/virología , Biopsia , Femenino , Infecciones por VIH/inmunología , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Neoplasias del Recto/virología , Recto/virología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: The aims of this study were to examine prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis. METHODS: MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (x400) and categorized as low (
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Adenocarcinoma/irrigación sanguínea , Antígenos CD/biosíntesis , Biomarcadores de Tumor/biosíntesis , Genes p53 , Neoplasias Ováricas/irrigación sanguínea , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Receptores de Superficie Celular/biosíntesis , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Anciano , Endoglina , Femenino , Factor 2 de Crecimiento de Fibroblastos , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Serpinas , Trombospondina 1 , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVES: Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement. MATERIALS AND METHODS: Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics. RESULTS: Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone. CONCLUSIONS: Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.
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Neoplasias del Ano/diagnóstico , Carcinoma in Situ/diagnóstico , ADN de Neoplasias/análisis , Regulación Neoplásica de la Expresión Génica , Genes p16/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Neoplasias del Ano/genética , Neoplasias del Ano/inmunología , Biopsia , Carcinoma in Situ/inmunología , Competencia Clínica , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
CONTEXT.: Feedback is the delivery of information based on direct observation that is meant to improve performance. Learning is at the heart of feedback, and as such, feedback is a required competency in pathology resident education. In the laboratory setting, the ability of laboratory professionals in all practice settings and experience levels to give and receive feedback is crucial to workflow and ultimately patient care. OBJECTIVE.: To summarize the importance of feedback, strategies for optimizing feedback exchange, and overcoming barriers to giving and receiving feedback. DATA SOURCES.: Peer-reviewed original articles, review articles, medical education literature, and published books on feedback and communication were reviewed to explore ideal methods of giving and receiving feedback and to identify common barriers to feedback exchange. CONCLUSIONS.: Medical education literature emphasizes techniques for giving feedback and describes barriers often encountered to feedback exchange in medical practice. Effective feedback requires that the giver, receiver, and environment be carefully considered. Likewise, each of these factors can impose barriers to feedback exchange. Various methods for giving feedback have been described. All feedback should address a specific behavior, be nonevaluative in nature, and be followed by confirmation of understanding and an action plan. Few articles describe the importance of receiving feedback. Receiving feedback can be difficult, but it is enhanced by learning to listen and making conscious decisions regarding implementing the messages heard. Giving and receiving feedback become easier with practice.
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Comunicación , Retroalimentación , Educación Médica/métodos , HumanosRESUMEN
Patients with malignant pleural mesothelioma and negative N2 stage lymph nodes may benefit from extrapleural pneumonectomy with adjuvant therapy. The objective of this study is to describe the use of EUS-FNA to determine N2 stage status in patients with mesothelioma and its impact in the management of such patients. Six patients (mean age, 62 yr; median age, 63 yr; range, 52-70 yr; 5 men; 1 woman) underwent EUS-FNA for staging of N2 lymph nodes from July 2000 to July 2006. Follow-up included operative notes, treatment summaries, and surgical pathology. Eight sites were aspirated: four subcarinal lymph nodes, three aorto-pulmonary window lymph nodes, and one paraesophageal mass. Two of 8 (25%) aspirates were positive for metastatic disease in two different patients. Two false negative EUS-FNAs were observed and were attributed to sampling error not diagnostic error. No complications were observed. EUS-FNA is a safe N2 node staging technique in patients with mesothelioma. A positive N2 lymph node by EUS-FNA may be a contraindication to definitive surgery in patients with malignant mesothelioma.
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Biopsia con Aguja Fina/métodos , Endosonografía/métodos , Mesotelioma/diagnóstico , Mesotelioma/patología , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/patología , Anciano , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Masculino , Mesotelioma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Selección de Paciente , Neoplasias Pleurales/cirugíaRESUMEN
Anal intraepithelial neoplasia (AIN) is a human papilloma virus related lesion. It has been shown that infection with high-risk human papilloma virus results in up-regulation of p16 and increased cellular proliferation. The objective of this study is to correlate p16 expression and cellular proliferation measured by Ki-67 staining with the degree of dysplasia in the anal canal and to determine the efficacy of these markers in diagnosing high-grade AIN. Seventy-five anal specimens from 55 patients (37 men; 18 women; mean age: 48 y; median: 44 y; range 25 to 96 y) were studied including 35 normal/reactive lesions, 23 low-grade AIN (AIN I and condyloma), and 17 high-grade AIN (AIN II and III). Immunostaining for p16 and Ki-67 was performed. Expression of p16 in AIN correlated with that of Ki-67 (P<0.001). High-grade AIN often demonstrated p16 staining in more than one-third of the thickness of the epithelium in a diffuse/continuous fashion. p16 expression in low-grade AIN was often restricted to the lower 1/3 of the epithelium and/or was focal and discontinuous. The expression of both p16 and Ki-67 correlated with the degree of dysplasia (P<0.01). When positive p16 staining was defined as the presence of diffuse/continuous staining in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of p16 as a marker for diagnosing high-grade AIN were 76%, 86%, and 84%, respectively. When positive Ki-67 staining was defined as the presence of nuclear staining in more than 25% of the cells in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of Ki-67 as a marker for diagnosing high-grade AIN were 71%, 84%, and 83% respectively. Both p16 and Ki-67 are reliable markers for diagnosing high-grade AIN.
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Neoplasias del Ano/diagnóstico , Genes p16 , Antígeno Ki-67/metabolismo , Infecciones por Papillomavirus/diagnóstico , Lesiones Precancerosas/diagnóstico , Infecciones Tumorales por Virus/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/metabolismo , Neoplasias del Ano/virología , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Femenino , Historia del Siglo XVII , Humanos , Inmunohistoquímica , Masculino , Infecciones por Papillomavirus/metabolismo , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/virología , Sensibilidad y Especificidad , Infecciones Tumorales por Virus/metabolismoRESUMEN
CONTEXT: - Current technologies including digital slide scanners and handheld devices can revolutionize clinical practice and pathology graduate medical education (GME). The extent to which these technologies are used in pathology GME is unknown. OBJECTIVES: - To determine the types of technologies used, usage amount, and how they are integrated into pathology residency/fellowship programs nationwide. DESIGN: - A 40-question online survey for residents/fellows was developed and administered via the Research Electronic Data Capture System after institutional review board approval. RESULTS: - Fifty-two program directors (37%) gave permission for participation. One-hundred seventy-one responses were received (18% response rate). Most respondents have access to personal technology (laptop = 78% [134 of 171]), smartphone = 81% [139 of 171], tablet = 49% [84 of 171]), and Web-based digital slide collections (82%, 141 of 171). Few residents are provided electronic devices by their programs (laptop = 22% [38 of 171], smartphone = 0.5% [1 of 171], and tablet = 12% [21 of 171]). Fifty-nine percent have access to digital slide scanners, 33% have access to a program-created database of digitized slides, and 52% use telepathology. Fifteen percent have access to asynchronous learning. Of those with access to video-recorded conferences, 89% review them. Program size was significantly positively correlated with resident access to program-provided laptops (P = .02) and tablets (P < .001), digital slide scanners (P = .01), and telepathology (P = .001). Of all devices, program-provided laptops are used most for professional work (60.5% use this device for more than 5 hours per day). CONCLUSIONS: - Most residents report access to multiple types of innovative technology, but incorporation of these tools within pathology training programs is highly variable. Opportunities for incorporating innovative technologies exist and could be further explored.