Immunohistochemical assessment of HER2 low breast cancer: interobserver reproducibility and correlation with digital image analysis.

PURPOSE: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC. METHODS: Fifty whole-slide biopsies of BC with HER2 IHC staining were evaluated, comprising 25 cases originally reported as IHC score 0 and 25 as 1 +. These slides were digitally scanned. Six pathologists with breast expertise independently reviewed and scored the scanned images, and DIA was applied. Agreement among pathologists and concordance between pathologist scores and DIA results were statistically analyzed using Kendall coefficient of concordance (W) tests. RESULTS: Substantial agreement among at least five of the six pathologists was found for 18 of the score 0 cases (72%) and 15 of the score 1 + cases (60%), indicating excellent interobserver agreement (W = 0.828). DIA scores were highly concordant with pathologist scores in 96% of cases (47/49), indicating excellent concordance (W = 0.959). CONCLUSION: Although breast subspecialty pathologists were relatively consistent in evaluating BC with HER2 IHC scores of 0 and 1 +, DIA may be a reliable supplementary tool to enhance the standardization and quantification of HER2 IHC assessment, especially in challenging cases where results may be ambiguous (i.e., scores 0-1 +). These findings hold promise for improving the accuracy and consistency of HER2 testing.

Interobserver reproducibility and interocular symmetry of the macular ganglion cell complex: assessment in healthy children using optical coherence tomography.

BACKGROUND: Assessment of interobserver reproducibility and interocular symmetry using optical coherence tomography (OCT)-based measurements of the macular ganglion cell complex (GCC) in healthy children facilitates interpretation of OCT data. We assessed the interobserver reproducibility and interocular symmetry of GCC and evaluated candidate determinants. METHODS: This was a cross-sectional study performed in a primary and tertiary health-care setting. A total of 126 healthy participants aged 5 to 18 years were eligible. GCC scans were performed by 4 operators using the Topcon 3D OCT-2000 device. Intraclass correlation coefficients (ICCs) were used to estimate reproducibility and symmetry. Cut-off points for symmetry were defined as the 95th percentile of the absolute interocular difference for 6 GCC parameters. Percentile distributions of interocular difference were generated based on age and difference in absolute interocular spherical equivalent (SE). RESULTS: The reproducibility ICC ranged from 0.96 to 0.98 for all 6 GCC parameters. Cut-off points for interocular symmetry of the superior and inferior quadrants and total macular retinal nerve fibre layer thickness (mRNFL) and macular ganglion cell layer-inner plexiform layer thickness were 3.5, 4.5, 3.0, 3.0, 2.5, and 2.5 µm respectively. A positive association was observed between the absolute interocular difference of SE and superior and total mRNFL symmetry values (p = 0.047 and p = 0.040, respectively). CONCLUSIONS: OCT measurements of GCC in healthy children show excellent reproducibility. Interocular differences in SE should be assessed when mRNFL differences exceed the 95% cut-off. These findings can contribute to establish reference values for interocular symmetry in paediatric GCC parameters.

Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration.

AIMS: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections. METHODS AND RESULTS: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot-spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799-0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot-spot method (0.83; 95% CI = 0.74-0.90) did not. Visually, interobserver concordance in location of selected hot-spots varies between cases. The median times for scoring were 9 and 6 min for global and hot-spot methods, respectively. CONCLUSIONS: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.

Intra-institutional second opinion diagnosis can reduce unnecessary surgery for indeterminate thyroid FNA: A preliminary report on 34 cases.

INTRODUCTION: Indeterminate diagnoses are rendered on 15%-30% of thyroid fine-needle aspirates (FNA). Thus, a second diagnostic opinion given by an outside expert pathologist is a common practice that facilitates a more appropriate clinical management. Conversely, the role of an intra-institutional second opinion diagnosis (iSOD), which is usually informally performed in-house, has not been well established. METHODS: To assess the contribution of iSOD, a retrospective series of 34 thyroid FNA diagnosed as follicular neoplasm/suspicious follicular neoplasm (FN/SFN) with matched histological follow-up and a malignancy rate of 17.6% was selected and independently reviewed by two cytopathologists (CYT1 and 2). Cases with discrepant diagnoses were referred to a third in-house senior cytopathologist for the iSOD. The malignancy rates (MR) obtained after single independent reviews and iSOD were compared. RESULTS: MR obtained after CYT1 and CYT2 re-screening was similar (14.28% and 19.04%, respectively) and did not improve the original MR (17.64%). Conversely, after the iSOD of discrepant diagnoses, the overall malignancy rate increased up to the 27.27%, potentially sparing unnecessary surgical procedures. CONCLUSIONS: Intra-institutional second opinion practice for "indeterminate" thyroid FNA avoids unnecessary surgeries and maximises the detection of malignant cases diagnosed as FN/SFN.

Interobserver reliability to interpret intrapartum electronic fetal heart rate monitoring: Does a standardized algorithm improve agreement among clinicians?

Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.

Interobserver Reliability of Milan and Modified Milan System for Reporting Salivary Gland Cytopathology: An Institutional Experience.

Background: In 2018, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published, defining a diagnostic categorization scheme. However, this system of classification was criticized due to its suboptimal diagnostic accuracy and low interobserver reliability. For these reasons, the modified Milan system was recently proposed by a few authors claiming it to be more clinically reliable. The present study aimed to analyze the interobserver reliability of MSRSGC and modified MSRSGC. Methods: A total of 100 salivary gland fine-needle aspirations were reviewed over a 1-year period and classified by two independent observers according to MSRSGC and modified MSRSGC. Interobserver reproducibility was estimated using observed agreement and chance-corrected agreement (Cohen's kappa). Results: An overall chance corrected agreement of 0.37 (fair) was obtained for the original Milan system and 0.41 (moderate) for the modified one. In addition, subcategories of modified MSRSGC performed better than the MSRSGC in terms of interobserver reliability. Conclusion: The present study suggests that modified MSRSGC should be accepted worldwide as the clinical relevance of any categorization scheme requires diagnostic accuracy along with excellent interobserver reproducibility.

Interobserver reproducibility of signal intensity ratio on magnetic resonance angiography for hemodynamic impact of intracranial atherosclerosis.

BACKGROUND: Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA. METHODS: Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other's readings: SIR=(mean poststenotic SI-mean background SI)/(mean prestenotic SI-mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index. RESULTS: A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92±.17 versus .93±.17; mean difference -.006±.09; P=.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland-Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers. CONCLUSIONS: SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

INTRODUCTION: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. MATERIALS AND METHODS: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. RESULTS: LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). CONCLUSIONS: Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Grading of Medullary Thyroid Carcinoma: an Interobserver Reproducibility Study.

Grade, based on proliferative activity and tumor necrosis, has recently been shown to be prognostic in medullary thyroid carcinoma (MTC) in multivariate analysis. The aim of this study was to evaluate the interobserver reproducibility of assessed grade in MTC. Three groups (each group included one resident/fellow and one attending pathologist) independently evaluated a cohort of 44 sporadic MTC. For each case, all available tumor slides were reviewed, and mitotic count and the presence of tumor necrosis were recorded. Ki-67 was performed, and the Ki-67 proliferative index was determined in the area of highest proliferative activity. Tumors were graded according to the recently published International Medullary Thyroid Carcinoma Grading System (IMTCGS). Kappa statistics were calculated for each individual criterion (mitotic count, Ki-67 proliferative index, and necrosis) and for assigned IMTCGS grade. For our cohort of 44 MTCs, the kappa statistic for mitotic count, Ki-67 proliferative index, and necrosis was 0.68, 0.86, and 0.89, respectively. The kappa statistic for assigned IMTCGS grade was 0.87. Our findings indicate that there was a strong level of agreement for assessment of grade in our cohort of MTC, indicating that grade as assessed by the IMTCGS is not only prognostic but also reproducible.

Comparison of Diagnostic Performances of Urine Cytology Before and After the Use of The Paris System Criteria: An Institutional Experience from Turkey.

BACKGROUND: Urine cytology remains to be the test of choice in the detection of high-grade urothelial carcinomas (HGUC) due to its favorable sensitivity. However, a significant rate of cases is reported under atypical/indeterminate categories, which result in a decrease in its specificity. Providing standardized cytologic criteria, one of the aims of The Paris System (TPS) is to reduce the use of indeterminate diagnoses and provide a higher predictive value in these categories. AIMS: We compared the diagnostic performances of TPS and our original reporting system, and also investigated the interobserver reproducibility of the cytologic criteria used. MATERIALS AND METHODS: A total of 386 urine samples were reviewed retrospectively. Original cytologic diagnoses have been made using similar cytologic features proposed by TPS. All slides were recategorized after the use of the cytologic criteria as described by TPS guideline. RESULTS: After TPS, specificity of the test increased from 39.6% to 63.5, sensitivity decreased from 92.5% to 88.8%, and diagnostic accuracy increased from 63.6% to 75%. The use of negative category increased threefold. Frequencies of indeterminate categories of atypical urothelial cells (AUC) and suspicious for HGUC (SHGUC) decreased by 36% and 56.5%, respectively. A subsequent detection of HGUC after AUC and SHGUC categories increased by 38% and 64%, respectively. Interobserver agreement for TPS categorization was 39%. CONCLUSIONS: TPS improved diagnostic accuracy of urine cytology by reducing the use of indeterminate categories, and resulted in increase in their predictive value for subsequent diagnosis of HGUC. However, reproducibility of diagnostic categories seemed to be imperfect.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

Low-Grade Ductal Carcinoma In Situ.

OBJECTIVES: We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. METHODS: Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. RESULTS: Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists' agreement was poor (κ = 0.235). CONCLUSIONS: Pathologists' reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.

Milan Interobserver Reproducibility Study (MIRST): Milan System 2018.

INTRODUCTION: Prior to the 2018 publication of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), a Web-based interobserver study was performed to evaluate MSRSGC reporting categories, identify cytomorphologic features that represent poor sources of agreement, and establish a baseline for future studies. MATERIAL AND METHODS: Study participants evaluated 75 images chosen from the MSRSGC image set, prior to the release of the Milan Atlas. Images spanned all diagnostic categories including typical and borderline cytomorphology. Participant demographics were collected on level of training, practice patterns, and experience. RESULTS: A total of 647 persons attempted access to the survey. Of these, 555 correctly answered the qualifying questions. Participants included: 16.5% ASCP Certified Cytotechnologists, 2.8% Specialist Cytotechnologists, 5.8% IAC Certified individuals, 14.3% Anatomic (AP) Certified Pathologists, 38.9% AP and Cytopathology Certified Pathologists, and 15.3% pathology trainees. Length of participant practice varied from 0 to 54 years. In our sample, 43.4% of participants came from academic centers, 17.6% from private hospitals; and 13.3% from commercial/private laboratories. Overall, 42% of respondents agreed with the reference interpretations of salivary gland lesions. The best agreement was seen in cytopathology certified pathologists. Among the MSRSGC categories, best agreement was found in Neoplasm-Benign (58.9%) and Non-Diagnostic (49.2%) categories, followed by Malignant (48.4%). The agreement rates for Salivary Gland Lesion of Uncertain Malignant Potential (SUMP) and Suspicious For Malignancy (SFM) were 23.6% and 22.7%, respectively. CONCLUSIONS: Similar to the reproducibility studies conducted for gynecologic and urinary cytopathology, the most important factor in diagnostic reproducibility was a priori classification of image difficulty, although people with higher certifications performed better.

Interobserver reproducibility of The Paris System of Reporting Urine Cytology on cytocentrifuged samples.

BACKGROUND: The Paris System of Reporting Urine Cytology aims to screen samples for HGUC and to provide a universally acceptable reporting format for urine cytology specimens. However, studies detailing the reproducibility of this system, especially on cyto-centrifuge preparations, are lacking. METHODS: 149 voided urine samples received in Department of Pathology were reviewed independently by five cytopathologists. To estimate the overall agreement, Gwet's AC and AC1statistics between each pair of raters were used. To measure the random error component, polychoric correlations were used. To assess the systematic error, Friedman test was used. RESULTS: There was moderately good inter-rater agreement between the raters. Gwets AC2 ranged between 0.67 and 0.89 for the classification of the cases once the sample was found adequate for assessment, while the Gwet's AC1 ranged between 0.61 and 0.94 in assessing for adequacy. There were significant systematic differences between raters in their thresholds for the different categories as well as in differentiating between an adequate and inadequate sample (P value by Friedman test <.001). The association between pathologists was moderately high (polychoric correlations ranging from 0.67 to 0.93). In the majority (108 of 149, 72.5%) of the cases, the range of differences between raters were of one category or less, suggesting satisfactory agreement, but having large disagreements in minority. CONCLUSION: The interobserver reproducibility for the Paris System is moderately good, and is suitable for adoption. It is limited by the lack of agreement as to what constitutes an adequate specimen and differing threshold for categorizing the lesions in differing groups.

Paris Interobserver Reproducibility Study (PIRST).

OBJECTIVES: In concert with the 2015 publication of The Paris System for Urinary Cytopathology (TPS), a Web-based interobserver study, co-sponsored by the American Society of Cytopathology (ASC) and International Academy of Cytology (IAC), was performed to determine diagnostic agreement among volunteer participants and with the TPS author consensus. MATERIAL AND METHODS: Participants at various levels of training and certification were recruited through national and international cytopathology professional societies. Although the survey was open to all comers, potential participants were screened by two basic cytopathology questions. Information was collected on the level of training, practice patterns, and experience. Study participants evaluated 85 images (previously unpublished) chosen from the TPS atlas. These images spanned all diagnostic categories. RESULTS: Of the 1993 attempts to access the survey, 1313 participants correctly answered the qualifying questions and were included in the survey. Respondents were concentrated in the United States, although many participants came from other countries. The majority of respondents were board-certified in anatomic pathology with cytopathology certification. A smaller number were cytotechnologists. Board-certified cytopathologists and specialist cytotechnologists outperformed other certifications. Practice type (academics versus non-academic), and country (US versus international) were not major factors in concordance. Diagnostic categories with the best agreement were Negative for High-Grade Urothelial Carcinoma (NHGUC; 71%), Low-Grade Urothelial Neoplasm (LGUN; 62%), and High-Grade Urothelial Carcinoma (HGUC; 57%). Indeterminate categories showed low concordance. CONCLUSIONS: The NHGUC, LGUN, and HGUC were most correlated with diagnostic agreement among observers. This study can serve as a baseline for future comparisons.

Taller de concordancia en la evaluación de imágenes capilaroscópicas / Reliability of nailfold videocapillaroscopy workshop

Introducción: la capilaroscopia es un método no invasivo que permite observar la microvasculatura en el área periungueal. Los resultados informados pueden ser altamente variables entre distintos observadores. A lo largo del tiempo surgieron métodos cuantitativos y semicuantitativos para mejorar la reproducibilidad. Objetivos: conocer el nivel de acuerdo intra e interobservador al informar los diferentes patrones capilaroscópicos en individuos con diferente nivel de entrenamiento. Materiales y métodos: estudio de corte transversal. Participaron médicos reumatólogos especialistas y en formación que habían realizado previamente un curso virtual de capacitación en capilaroscopia. Recibieron 40 imágenes capilaroscópicas proyectadas en una presentación de PowerPoint y debían responder a través de un cuestionario digital. Se evaluó la concordancia de respuestas intra e interobservador. Resultados: se encontró un alto nivel de concordancia global con un kappa 0,66 IC 95% (0,63-0,70) p<0,0000. También en otros grupos como reumatólogos en formación: kappa 0,65 IC 95% (0,60-0,71) p=0,0000, y médicos reumatólogos: kappa 0,67 IC 95% (0,62-0,72) p=0,0000. Conclusiones: el nivel de concordancia encontrado fue globalmente alto, independientemente del nivel de entrenamiento de los profesionales, y de ser o no reumatólogo. La concordancia fue superior cuando se comparó a quienes tenían más de 4 años de experiencia en la realización de videocapilaroscopia.

Introduction: videoapillaroscopy is a non-invasive method that allows the observation of the microvasculature in the periungual area. Reported results can be highly variable between different observers. Over time, quantitative and semi-quantitative methods emerged to improve reproducibility. Objetives: to know the level of intra and interobserver agreement when reporting the different capillaroscopic patterns in individuals with different levels of training. Materials and methods: cross section study. Specialist rheumatologists and those in training who had previously completed a virtual capillaroscopy training course participated. They received 40 capillaroscopic images projected in a PowerPoint presentation and had to issue their response through a digital questionnaire. Concordance of intra and interobserver responses was evaluated. Results: a high level of global agreement was found with a kappa 0.66 CI 95% (0.63-0.70) p<0.0000, also in other groups such as rheumatologists in training: kappa 0.65 CI 95% (0.60-0.71) p=0.0000, physicians rheumatologists: kappa 0.67 95% CI (0.62-0.72) p=0.0000. Conclusions: the level of agreement found was globally high, regardless of the level of training of the professionals, and whether or not they were a rheumatologist. Concordance was higher when compared to those who had more than 4 years of experience performing videocapillaroscopy.

Interobserver reproducibility for HER2/neu immunohistochemistry: A comparison of reproducibility for the HercepTest™ and the 4B5 antibody clone.

BACKGROUND: IHC results for HER2/neu vary with replicate testing using the same antibody clone and when alternate clones are utilized. A number of factors appear to be responsible for this variability, including fixation times, equipment utilized and training and experience of staff. A number of studies have documented interobserver variability for a single antibody clone but few have evaluated reproducibility between antibody clones and which clones demonstrate the highest degree of interobserver reproducibility. DESIGN: We studied a series of 93 cases stained by both the HercepTest™ and the 4B5 clone for interobserver reproducibility. Formalin-fixed, paraffin-embedded sections were stained by the immunohistochemical technique using the manufactures directions for both the HercepTest™ and the 4B5 clone. FISH testing was performed on formalin-fixed paraffin embedded sections according to the PathVysion HER-2 DNA probe kit instructions. RESULTS: Absolute agreement rate for Hercep was 85%. Absolute agreement for 4B5 was 69%. This difference was statistically significant (p<0.0001). The chance-corrected agreement (weighted kappa) for the HercepTest™ was 79% and 71% for 4B5 (p<0.0001). Absolute agreement between antibody clones was 58% with the chance corrected agreement being 51%. Absolute agreement of 4B5 with FISH was significantly greater than that of the HercepTest™ (54% vs 35%). CONCLUSION: Agreement between evaluators was greater with the HercepTest. However, agreement with FISH results was superior for the 4B5 clone. Interobserver agreement was less than the 95% agreement threshold recommended by the ASCO/CAP guidelines for development of a new testing method for HER2 evaluation.

Nephrometry scores: interobserver reproducibility and perioperative factors prediction.

OBJECTIVES: To validate the relation of the nephrometry scores in a series of patients who underwent partial nephrectomy with perioperative parameters and the urologist-radiologist reproducibility. MATERIAL AND METHODS: A retrospective study of open and laparoscopic partial nephrectomy patients performed between 2005 and 2012 registered in prospective filled out database. An urologist and a radiologist calculated the R.E.N.A.L., PADUA and C-index for 86 patients. We carried out a comparative study of the results using the Spearman and Pearson correlation indexes. RESULTS: Distribution according to the complexity of the tumors with the RENAL calculation was: 42 (49%) low, 35 (41%) moderated and 9 (11%) high complexity. According to PADUA: 35 (41%) low complexity, 32 (37%) intermediate and 19 (22%) high. No statistically significant correlation was found for the appearance of operative complications and the pathology results in case of RENAL and PADUA. A correlation was found in the case of PADUA in relation to the warm ischemia time. Positive correlation according to Spearman's index was found in RENAL, PADUA and C-index between urologist and radiologist evaluations. CONCLUSIONS: Nephrometry scores can be a useful tool to plan the surgical technique or approach. However, it is not clear if they are really predictors of surgical or pathologic parameters. The correlation between the urologist and radiologist seems to be sufficient to recommend their use by both specialties.

Reproducibility of the Johns Hopkins Hospital template for urologic cytology samples.

INTRODUCTION: Cytologic screening for urothelial carcinoma is fraught with low sensitivity, a high indeterminate rate, and until recently, poor standardization of terminology. The Johns Hopkins Hospital John K. Frost Cytopathology Laboratory has recently developed and published a template for reporting urine cytopathology; herein, we evaluate its interobserver reproducibility. MATERIALS AND METHODS: Two sets of 100 cases each were deidentified; each set was reviewed by 5 of 10 observers in a randomized order at the direction of computerized data collection software that tracked observation time as well as observer classification of the atypia-no atypia, atypia (AUC-US), or atypia suggestive of high-grade urothelial carcinoma (AUC-H). Specific morphologic features were also recorded. Cases were grouped into low-, intermediate-, and high-agreement based on the number of observers who made the assessment. The findings were correlated against clinical outcomes. RESULTS: High agreement among observers about the presence or absence of high-grade features was possible in approximately two-thirds of indeterminate urine cases. Time and order did not factor significantly into observer propensity for identifying atypical features or favoring either AUC-US or AUC-H, and cases with high agreement about the presence of high-grade features were more likely to have a malignant follow-up. Furthermore, AUC-H diagnoses based on 2 or more high-grade features had a significantly higher malignancy risk than AUC-US diagnoses did. CONCLUSIONS: AUC-H is a valid diagnostic category with specific, reproducibly identified features that portend a higher risk of malignancy than the findings of AUC-US.