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1.
Int J Gynecol Pathol ; 40(6): 587-596, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-33720082

ABSTRACT

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.


Subject(s)
Adenocarcinoma , Endometrial Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , DNA Mutational Analysis , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Female , Humans , Immunohistochemistry , Mutation , beta Catenin/genetics
2.
J Natl Compr Canc Netw ; 16(2): 201-209, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29439179

ABSTRACT

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.


Subject(s)
Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genomics , Animals , Disease Management , Endometrial Neoplasms/mortality , Endometrial Neoplasms/therapy , Female , Genetic Association Studies/methods , Genomics/methods , Humans , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy
3.
Gynecol Oncol ; 139(1): 23-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26260910

ABSTRACT

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.


Subject(s)
Cystadenocarcinoma, Serous/blood supply , Cystadenocarcinoma, Serous/genetics , Ovarian Neoplasms/blood supply , Ovarian Neoplasms/genetics , Adult , Aged , Antigens, CD/analysis , Biomarkers, Tumor/genetics , Cystadenocarcinoma, Serous/pathology , Endoglin , Female , Gene Expression , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neovascularization, Pathologic/genetics , Oligonucleotide Array Sequence Analysis , Ovarian Neoplasms/pathology , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Prognosis , Proportional Hazards Models , Receptors, Cell Surface/analysis , Survival Rate
5.
J Low Genit Tract Dis ; 15(2): 146-57, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21317805

ABSTRACT

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.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Neoplasm Invasiveness/pathology , Neoplasm Staging/methods , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/diagnosis , Carcinoma, Squamous Cell/diagnosis , Female , Humans , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Neoplasm Invasiveness/diagnosis , Uterine Cervical Neoplasms/diagnosis
6.
Hum Pathol ; 116: 63-72, 2021 10.
Article in English | MEDLINE | ID: mdl-34310982

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Neuroendocrine/pathology , Liver Neoplasms/pathology , Mixed Tumor, Malignant/pathology , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Neuroendocrine/etiology , Female , Humans , Liver Cirrhosis/complications , Liver Neoplasms/etiology , Male , Middle Aged , Mixed Tumor, Malignant/etiology
7.
Cancer Cytopathol ; 129(7): 517-525, 2021 07.
Article in English | MEDLINE | ID: mdl-33481348

ABSTRACT

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.


Subject(s)
Cytodiagnosis , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Pathologists , Female , Humans , Middle Aged , Reproducibility of Results
8.
Cancer Invest ; 28(9): 969-77, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20873988

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Female , Humans , Logistic Models , Multivariate Analysis , Neoplasm Recurrence, Local , Prognosis , Severity of Illness Index
9.
Gynecol Oncol ; 116(3): 556-62, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20006900

ABSTRACT

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.


Subject(s)
Lymphocytes, Tumor-Infiltrating/immunology , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , T-Lymphocytes, Regulatory/immunology , Adult , Aged , Aged, 80 and over , Antigen Presentation , Female , Gene Expression/immunology , Humans , Lymphocytes, Tumor-Infiltrating/pathology , Middle Aged , Neoplasm Metastasis , Ovarian Neoplasms/genetics , Phenotype , T-Lymphocytes, Regulatory/pathology , Young Adult
10.
Reprod Biomed Online ; 21(1): 4-5, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20627684

ABSTRACT

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.


Subject(s)
Endometriosis/etiology , Endometriosis/embryology , Endometriosis/physiopathology , Endometrium/pathology , Female , Humans
11.
Int J Gynecol Pathol ; 29(3): 212-27, 2010 May.
Article in English | MEDLINE | ID: mdl-20407319

ABSTRACT

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.


Subject(s)
Adenocarcinoma, Follicular/pathology , Ovarian Neoplasms/pathology , Struma Ovarii/pathology , Adenocarcinoma, Follicular/surgery , Adolescent , Adult , Child , Female , Histocytochemistry , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/surgery , Struma Ovarii/surgery , Young Adult
12.
Int J Gynecol Pathol ; 29(1): 69-78, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19952933

ABSTRACT

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.


Subject(s)
Paget Disease, Extramammary/pathology , Vulvar Neoplasms/pathology , Aged , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Paget Disease, Extramammary/metabolism , Paget Disease, Extramammary/surgery , Prognosis , Risk Factors , Vulvar Neoplasms/metabolism , Vulvar Neoplasms/surgery
13.
J Low Genit Tract Dis ; 14(2): 90-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20354415

ABSTRACT

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.


Subject(s)
Anal Canal/pathology , HIV Infections/complications , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Rectal Neoplasms/epidemiology , Rectum/pathology , Adult , Aged , Anal Canal/virology , Biopsy , Female , HIV Infections/immunology , Histocytochemistry , Humans , Male , Middle Aged , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/complications , Rectal Neoplasms/virology , Rectum/virology , Retrospective Studies , United States/epidemiology
14.
Gynecol Oncol ; 112(3): 469-74, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19135712

ABSTRACT

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 (or=upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined. RESULTS: Of 106 evaluable cases, 25% exhibited high CD31-MVD (>24.25 vessels/high power field [HPF]) or high CD105-MVD (>19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking status and treatment regimen, high versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR]=1.873; 95% confidence interval [CI]: 1.102-3.184; p=0.020), but not death (HR=1.125; 95% CI: 0.654-1.935; p=0.670) whereas CD31-MVD was not associated with risk of disease progression (HR=1.578; 95% CI=0.918-2.711; p=0.099) or death (HR=1.678; 95% CI=0.957-2.943; p=0.071). CD31-MVD was correlated with CD105-MVD (p=0.001) and MASPIN (p=0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1. CONCLUSIONS: High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates.


Subject(s)
Adenocarcinoma/blood supply , Antigens, CD/biosynthesis , Biomarkers, Tumor/biosynthesis , Genes, p53 , Ovarian Neoplasms/blood supply , Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis , Receptors, Cell Surface/biosynthesis , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Aged , Endoglin , Female , Fibroblast Growth Factor 2 , Humans , Immunohistochemistry , Middle Aged , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Serpins , Thrombospondin 1 , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1
15.
J Low Genit Tract Dis ; 13(3): 145-53, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19550211

ABSTRACT

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.


Subject(s)
Anus Neoplasms/diagnosis , Carcinoma in Situ/diagnosis , DNA, Neoplasm/analysis , Gene Expression Regulation, Neoplastic , Genes, p16/physiology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/analysis , Anus Neoplasms/genetics , Anus Neoplasms/immunology , Biopsy , Carcinoma in Situ/immunology , Clinical Competence , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Observer Variation , Retrospective Studies
16.
Arch Pathol Lab Med ; 143(2): 244-250, 2019 02.
Article in English | MEDLINE | ID: mdl-30102068

ABSTRACT

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.


Subject(s)
Communication , Feedback , Education, Medical/methods , Humans
17.
Diagn Cytopathol ; 36(1): 32-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18064685

ABSTRACT

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.


Subject(s)
Biopsy, Fine-Needle/methods , Endosonography/methods , Mesothelioma/diagnosis , Mesothelioma/pathology , Pleural Neoplasms/diagnosis , Pleural Neoplasms/pathology , Aged , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Male , Mesothelioma/surgery , Middle Aged , Neoplasm Staging/methods , Patient Selection , Pleural Neoplasms/surgery
18.
Am J Surg Pathol ; 31(4): 555-61, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17414102

ABSTRACT

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.


Subject(s)
Anus Neoplasms/diagnosis , Genes, p16 , Ki-67 Antigen/metabolism , Papillomavirus Infections/diagnosis , Precancerous Conditions/diagnosis , Tumor Virus Infections/diagnosis , Adult , Aged , Aged, 80 and over , Anus Neoplasms/metabolism , Anus Neoplasms/virology , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , Female , History, 17th Century , Humans , Immunohistochemistry , Male , Papillomavirus Infections/metabolism , Precancerous Conditions/metabolism , Precancerous Conditions/virology , Sensitivity and Specificity , Tumor Virus Infections/metabolism
19.
Arch Pathol Lab Med ; 141(3): 431-436, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28157405

ABSTRACT

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.


Subject(s)
Computers , Education, Medical, Graduate/methods , Internship and Residency , Humans , Surveys and Questionnaires
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