Longitudinal evaluation of interobserver and intraobserver agreement of cervical intraepithelial neoplasia diagnosis among an experienced panel of gynecologic pathologists

Histologic diagnoses of cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3) are the key end points in clinical trials that evaluate the efficacy of a prophylactic quadrivalent human papillomavirus vaccine against cervical cancer. Adjudication of end points uses a panel of 4 pathologists. Quality control slides (n=185) from a nonclinical trial study with preestablished gold standard CIN diagnoses were used to characterize the panel's agreement on CIN diagnoses and monitor performance longitudinally. At 3-month intervals over 2 years, 1 of 6 different batches of quality control slides (n=30-31) was included with clinical trial slides for independent review by each of the 4 panelists. Unweighted kappas (kappa) were estimated within each panelist pair by dichotomizing the diagnoses as CIN+ versus non-CIN+ (including normal, unsatisfactory, and atypical immature metaplasia) or CIN 2/3+ versus non-CIN 2/3+ (including normal, unsatisfactory, atypical immature metaplasia, and CIN 1). Quadratic weighted kappa was calculated within each panelist pair using 4 diagnostic categories: normal, CIN 1, CIN 2, and CIN 3 or worse. Substantial interobserver agreement was observed (weighted kappa=0.765 to 0.865). Agreement with weighted kappa=0.779 to 0.887 was observed between the individual panelists and the gold standard, which is almost perfect agreement by Landis-defined categories. Intraobserver agreement was very high (weighted kappa=0.756 to 0.883). Some fluctuation in intraobserver and interobserver agreement was observed over the study period but there was no decreasing time trend. These data indicate that the interpretation of histologic end points used in the quadrivalent vaccine clinical trial program is highly valid and reliable.     

Gastric dysplasia: the Padova international classification

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.     

Diagnosing endometrial hyperplasia: why is it so difficult to agree?

Current World Health Organization classification of endometrial hyperplasia is problematic because of poor diagnostic reproducibility. We sought to determine factors that cause diagnostic disagreement in a review of 2601 endometrial specimens. Blinded random specimens of normal endometrium, hyperplasias, and carcinoma were reviewed by 2 pathologists, with review by a third pathologist in cases with disagreement. All cases of endometrial hyperplasia or carcinoma were scored for degree of glandular crowding, architectural complexity, and cytologic atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or endometrial polyp were also scored. The overall kappa for agreement was 0.71, with a lower kappa of 0.36 when cases called "no hyperplasia" were excluded. The percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and 57.5% for adenocarcinoma. Cases categorized as "low volume hyperplasia" had more diagnostic disagreement than "high volume," (62% vs. 39%, P=0.003). Similarly, cases called "scant" had more diagnostic disagreement than "not scant" (65% vs. 57%, P=0.013). The histologic feature associated with the most diagnostic disagreement was cytologic atypia (P<0.0001). Architectural crowding, architectural complexity, or the presence of a polyp were all associated with diagnostic disagreement (P<0.0001). High diagnostic disagreement in endometrial hyperplasia is related to both sample adequacy and interpretation of histologic features present. Although obtaining additional tissue may increase diagnostic reproducibility, differences in interpretation of key histologic features like cytologic atypia remain major factors contributing to diagnostic disagreement.     

Reproducibility of the Banff classification in subclinical kidney transplant rejection

The Banff classification for kidney allograft pathology has proved to be reproducible, but its inter and intraobserver agreement can vary substantially among centres. The aim of this study was to evaluate Banff reproducibility of surveillance renal allograft biopsies among renal pathologists from different transplant centres. This study included 32 renal transplant patients with stable graft function. Biopsies were performed 2 and 12 months post-transplant. Histology was interpreted according to the Banff schema by three renal pathologists, and inter and intraobserver agreement were measured. The best reproducibility was obtained for the presence or absence of acute rejection (AR), with kappa values ranging from moderate (kappa = 0.47; p = 0.006) to good (kappa = 0.72; p = 0.0001). However, the agreement for 'suspicious for AR' category was poor between all observers. For scoring and grading interstitial inflammation and intimal arteritis the agreement were poor and moderate, respectively. Reproducibility for the presence or absence of chronic allograft nephropathy (CAN) was heterogeneous, ranging from poor (kappa = 0.13; p = NS) to moderate (kappa = 0.56; p = 0.007). Scoring chronic changes such as fibrous intimal thickening gave a reasonable interobserver agreement. Intraobserver reproducibility was good for presence or absence of AR, but was poor for the diagnosis of CAN. In conclusion, histologic analysis of stable renal allografts based on Banff criteria showed a good agreement for the diagnosis of AR and a reasonable kappa for CAN, but reproducibility for scoring and grading showed a substantial interobserver variation.     

Interobserver and intraobserver variability in the diagnosis of hydatidiform mole

Surgical pathologists often encounter hydropic villi in products of conception at the first trimester and must determine whether the villi represent complete hydatidiform mole (CM), partial hydatidiform mole (PM), or hydropic abortion (HA). The distinction between these is important for determining the appropriate treatment of patients. This study assessed interobserver and intraobserver variability in the histologic diagnosis of hydatidiform mole among 5 placental pathologists. To evaluate interobserver variability, one representative slide from each of 50 mixed cases of PM, CM, and HA of the first trimester were circulated among 5 placental pathologists. All pathologists used the same histologic criteria by Szulman and Surti. For the second round, the same cases were submitted with DNA ploidy data. For the third round, the slides were recoded and distributed to assess intraobserver agreement. Kappa (kappa) value was calculated for the interobserver agreement in the first and second rounds. There was agreement among 4 or 5 pathologists for only 30 of 50 cases in the first round. There were problems in differentiating between PM and HA in most of the remaining 20 cases. The kappa values varied from poor (kappa = -0.104) to excellent (kappa = 0.761) in the first round. In the second round, there was agreement in 39 of 50 cases and the level of agreement remarkably increased, ranging from fair to good (kappa = 0.552) to excellent (kappa = 0.851). The number of discrepant cases, PM versus HA, was reduced to 4. In 7 cases, there were difficulties in distinguishing CM from HA. The intraobserver agreement ranged from 50% to 90%. Poor interobserver agreement was demonstrated when histology alone was used for diagnosis. Discordance was most frequently seen in PM versus HA and resulted from difficulty in evaluating trophoblastic hyperplasia. Polar trophoblastic growth seen in HA could also be observed in PM. The addition of ploidy data resulted in a significant improvement in concordance. Ploidy study is useful in equivocal cases. Significant interobserver and intraobserver variability was observed even among placental pathologists. New histologic criteria adaptable to differentiation of early lesions are needed.     

Intraobserver and interobserver reliability of Kalamchi and Macewen's classification system for evaluation of avascular necrosis of the femoral head in developmental hip dysplasia

This study evaluates the intraobserver and interobserver reliability of the Kalamchi and MacEwen's classification system of avascular necrosis of the femoral head. Radiographs of 48 developmentally dysplastic hips that had an average follow-up of 40.5 months (range: 36 to 52 months) and that had been treated by the same operative technique were interpreted twice by four experienced pediatric orthopaedic surgeons. When the absence or presence of avascular necrosis was taken into consideration the average intraobserver agreement percentage and kappa coefficient were 86% and 0.71, respectively. The average interobserver agreement percentage and kappa coefficient were 83% and 0.66, respectively. When the agreement on the type of avascular necrosis was analyzed, the average intraobserver agreement percentage and kappa coefficient were 85% and 0.74, respectively. The average interobserver agreement percentage and kappa coefficient were 81% and 0.66, respectively. No statistically significant difference was found between the rates of avascular necrosis of four observers. The Kalamchi and MacEwen's classification system was found to be reliable and reproducible.     

Two and three-dimensional computed tomography for the classification and management of distal humeral fractures. Evaluation of reliability and diagnostic accuracy

BACKGROUND: Complex fractures of the distal part of the humerus can be difficult to characterize on plain radiographs and two-dimensional computed tomography scans. We tested the hypothesis that three-dimensional reconstructions of computed tomography scans improve the reliability and accuracy of fracture characterization, classification, and treatment decisions. METHODS: Five independent observers evaluated thirty consecutive intra-articular fractures of the distal part of the humerus for the presence of five fracture characteristics: a fracture line in the coronal plane; articular comminution; metaphyseal comminution; the presence of separate, entirely articular fragments; and impaction of the articular surface. Fractures were also classified according to the AO/ASIF Comprehensive Classification of Fractures and the classification system of Mehne and Matta. Two rounds of evaluation were performed and then compared. Initially, a combination of plain radiographs and two-dimensional computed tomography scans (2D) were evaluated, and then, two weeks later, a combination of radiographs, two-dimensional computed tomography scans, and three-dimensional reconstructions of computed tomography scans (3D) were assessed. RESULTS: Three-dimensional computed tomography improved both the intraobserver and the interobserver reliability of the AO classification system and the Mehne and Matta classification system. Three-dimensional computed tomography reconstructions also improved the intraobserver agreement for all fracture characteristics, from moderate (average kappa [kappa2D] = 0.554) to substantial agreement (kappa3D = 0.793). The addition of three-dimensional images had limited influence on the interobserver reliability and diagnostic characteristics (sensitivity, specificity, and accuracy) for the recognition of specific fracture characteristics. Three-dimensional computed tomography images improved intraobserver agreement (kappa2D = 0.62 compared with kappa3D = 0.75) but not interobserver agreement (kappa2D = 0.24 compared with kappa3D = 0.28) for treatment decisions. CONCLUSIONS: Three-dimensional reconstructions improve the reliability, but not the accuracy, of fracture classification and characterization. The influence of three-dimensional computed tomography was much more notable for intraobserver comparisons than for interobserver comparisons, suggesting that different observers see different things in the scans-most likely a reflection of the training, knowledge, and experience of the observer with regard to these relatively uncommon and complex injuries.     

Intraobserver and interobserver variability and spatial differences in histologic examination of carotid endarterectomy specimens

INTRODUCTION: Studies using histologic examination and protein analysis of atherosclerotic plaques are increasingly being performed, but reproducibility of plaque histology and variation of plaque composition among different parts of the plaque, which are key to reliability of these studies, are relatively unexplored. Therefore, this study investigated the intraobserver and interobserver variability of plaque histology and spatial variability in plaque composition. METHODS: Atherosclerotic plaques (n = 100) obtained during carotid endarterectomy were divided into 0.5-cm segments. Paraffin sections were stained and semiquantitatively analyzed (four categories: no, minor, moderate, and heavy) for fat, macrophages, smooth muscle cells, collagen, calcification, thrombus, and overall phenotype. First, to determine the intraobserver and interobserver reproducibility, two independent observers independently analyzed the plaques. Second, to investigate spatial variability in plaque composition, histologic appearances of the culprit lesions (0-segment) were compared with the histologic appearances of adjacent (+5 mm) and more distant (+10 mm) plaque segments of 30 specimens. RESULTS: The kappa values for intraobserver variability of fat, macrophages, smooth muscle cells, collagen, calcifications, thrombus, and overall phenotype were 0.83, 0.85, 0.71, 0.63, 0.81, 0.80, and 0.86, respectively, and kappa values for interobserver variability were 0.68, 0.74, 0.54, 0.59, 0.82, 0.75, and 0.71, respectively. Comparison of the histologic scorings of adjacent segments revealed a mean kappa of 0.40 (range, 0.33 to 0.60). When the culprit segment was compared with the more distant segment, the mean kappa was 0.24; however, in 91% of cases, the difference between the culprit segment and the distal segment was one category or less. CONCLUSION: Semiquantitative analysis of carotid atherosclerotic plaque histology was well reproducible, both intraobserver and interobserver. Although variation between different plaque segments in histologic appearance was observed, differences were small in almost all cases. Variability in histologic examination needs to be taken into account in studies comparing plaque imaging with histopathology and plaque research studies.     

Interobserver and intraobserver reliability of two classification systems for intra-articular calcaneal fractures

BACKGROUND: For a fracture classification to be useful it must provide prognostic significance, interobserver reliability, and intraobserver reproducibility. Most studies have found reliability and reproducibility to be poor for fracture classification schemes. The purpose of this study was to evaluate the interobserver and intraobserver reliability of the Sanders and Crosby-Fitzgibbons classification systems, two commonly used methods for classifying intra-articular calcaneal fractures. METHODS: Twenty-five CT scans of intra-articular calcaneal fractures occurring at one trauma center were reviewed. The CT images were presented to eight observers (two orthopaedic surgery chief residents, two foot and ankle fellows, two fellowship-trained orthopaedic trauma surgeons, and two fellowship-trained foot and ankle surgeons) on two separate occasions 8 weeks apart. On each viewing, observers were asked to classify the fractures according to both the Sanders and Crosby-Fitzgibbons systems. Interobserver reliability and intraobserver reproducibility were assessed with computer-generated kappa statistics (SAS software; SAS Institute Inc., Cary, North Carolina). RESULTS: Total unanimity (eight of eight observers assigned the same fracture classification) was achieved only 24% (six of 25) of the time with the Sanders system and 36% (nine of 25) of the time with the Crosby-Fitzgibbons scheme. Interobserver reliability for the Sanders classification method reached a moderate (kappa = 0.48, 0.50) level of agreement, when the subclasses were included. The agreement level increased but remained in the moderate (kappa = 0.55, 0.55) range when the subclasses were excluded. Interobserver agreement reached a substantial (kappa = 0.63, 0.63) level with the Crosby-Fitzgibbons system. Intraobserver reproducibility was better for both schemes. The Sanders system with subclasses included reached moderate (kappa = 0.57) agreement, while ignoring the subclasses brought agreement into the substantial (kappa = 0.77) range. The overall intraobserver agreement was substantial (kappa = 0.74) for the Crosby-Fitzgibbons system. CONCLUSIONS: Although intraobserver kappa values reached substantial levels and the Crosby-Fitzgibbons system generally showed greater agreement, we were unable to demonstrate excellent interobserver or intraobserver reliability with either classification scheme. While a system with perfect agreement would be impossible, our results indicate that these classifications lack the reproducibility to be considered ideal.     

A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis

The International Federation of Gynecology and Obstetrics (FIGO) grading of uterine endometrial endometrioid carcinoma requires evaluation of histologic features that can be difficult to assess, including recognition of small amounts of solid growth, distinction of squamous from nonsquamous solid growth, and assessment of degree of nuclear atypia. The authors describe a novel, binary architectural grading system that uses low-magnification assessment of amount of solid growth, pattern of invasion, and presence of necrosis to divide endometrioid carcinomas into low- and high-grade tumors. The authors analyzed its performance for predicting prognosis and with respect to intra- and interobserver reproducibility. A total of 141 endometrioid carcinomas from hysterectomy specimens were graded according to the FIGO system, nuclear grading, and the binary architectural system. A tumor was classified as high grade if at least two of the following three criteria were present: (1) more than 50% solid growth (without distinction of squamous from nonsquamous epithelium); (2) a diffusely infiltrative, rather than expansive, growth pattern; and (3) tumor cell necrosis. For tumors that were confined to the endometrium, only percent solid growth and necrosis were evaluated, and those with both solid growth of more than 50% and necrosis were considered high grade. All tumors were graded independently by three pathologists on two separate occasions. Both inter- and intraobserver agreement using the binary grading system (kappa = 0.65 and 0.79) were superior compared with FIGO (kappa = 0.55 and 0.67) and nuclear grading (kappa = 0.22 and 0.41). The binary grading system stratified patients into three distinct prognostic groups. Patients with stage I low-grade tumors with invasion confined to the inner half of the myometrium (stages IA and IB) had a 100% 5-year survival rate. Patients with low-grade tumors that invaded beyond the outer half of the myometrium (stage IC and stages II-IV) and those with high-grade tumors with invasion confined to the myometrium (stages IB and IC) had a 5-year survival rate of 67% to 76%. In striking contrast to patients with advance-stage low-grade tumors, patients with advance-stage high-grade tumors had a 26% 5-year survival rate. This binary grading system has advantages over FIGO and nuclear grading that permit greater interobserver and intraobserver reproducibility and should be tested in other studies of endometrial endometrioid carcinomas to validate its reproducibility and use for segregating patients into different prognostic groups.     

Evaluation of the reliability of classification systems used for distal radius fractures

The objective of this investigation was to evaluate the reliability of classification systems by determining inter- and intraobserver agreement in displaced distal radius fractures. Radiographs of 32 patients (21 men and 11 women with a mean age of 41.6 years) who presented with a displaced distal radius fracture were classified by 9 orthopedic surgeons (5-25 years experience) using 5 different classification systems (Fernandez, AO, Frykman, Melone, and Universal Classification systems) twice with 20-day intervals. The results were processed with kappa statistics and used in assessment of inter- and intraobserver agreement of the classification systems. When classification systems were compared, the highest kappa coefficient in intraobserver agreement was determined in Universal classification (0.621). Fernandez (0.474), AO (0.309), Frykman (0.305), and Melone classification systems (0.262) followed the Universal system respectively. Kappa statistical results were evaluated using the Landis Koch score system for the assessment of interobserver agreement. According to the Landis Koch score system, the results were insufficient in all classification systems. Fernandez classification system had the highest interobserver agreement (0.235) and Melone classification system had the lowest interobserver agreement (0.056). According to the results of our study, the systems used to classify the displaced distal radial fractures are insufficient. A new classification system that ensures the 3-dimensional assessment of the fracture is more user-friendly and a high inter- and intraobserver agreement is necessary.     

Interobserver and intraobserver reliability of the japanese orthopaedic association scoring system for evaluation of cervical compression myelopathy

STUDY DESIGN: The inter- and intraobserver reliabilities of an assessment scale for cervical compression myelopathy were examined statistically. This scoring system consists of seven categories: motor function of fingers, shoulder and elbow, and lower extremity; sensory function of upper extremity, trunk and lower extremity; and function of the bladder. It evaluates the severity of myelopathy by allocating points based on degree of dysfunction in each category. OBJECTIVES: To determine the inter- and intraobserver reliabilities of the revised scoring system (17 - 2 points) for cervical compression myelopathy proposed by the Japanese Orthopedic Association. SUMMARY OF BACKGROUND DATA: Several scales to assess clinical outcome from treatment of cervical compression myelopathy have been proposed. Most of these scales include items evaluated by observers. However, no system, including the Japanese Orthopedic Association scoring system, has yet been validated in terms of interobserver reliability. METHODS: From five different university hospitals, 10 spine surgery specialists, 10 orthopedic surgeons who had just passed the board examination of the Japanese Orthopedic Association, and 13 residents in the first or second year of orthopedic residency programs were chosen. The participants in this study were 29 patients with myelopathy secondary to ossification of the posterior longitudinal ligament selected from five participating university hospitals. Several surgeons interviewed each patient twice at intervals of 1 to 6 weeks. Inter- and intraobserver reliabilities of the total score for all categories were evaluated by the intraclass correlation coefficient. The extension of the kappa coefficient of Kraemer also was calculated for each category to assess reliability of multivariate categorical data. RESULTS: The interobserver reliability of the total score for the first interview (intraclass correlation coefficient = 0.813) and the intra- and interobserver reliabilities of the total score (intraclass correlation coefficient = 0.826) were high. The level of experience and the hospital slightly affected the reliability of the Japanese Orthopedic Association scoring system. The kappa values for intraobserver data generally were high in each category, whereas the kappa values for interobserver data were relatively low for the categories of shoulder-elbow motor function and lower extremity sensory function. CONCLUSIONS: The inter- and intraobserver reliabilities of the Japanese Orthopedic Association scoring system for cervical myelopathy were high, suggesting that this system is useful for assessment of cervical myelopathy in comparative studies of treatment.     

Observer reliability in the arthroscopic classification of osteoarthritis of the knee

We studied 19 videotaped knee arthroscopies in 19 patients with mild to moderate osteoarthritis (OA) of the knee in order to compare the intraobserver and interobserver reliability and the patterns of disagreement between four orthopaedic surgeons. The classifications of OA of Collins, Outerbridge and the French Society of Arthroscopy were used. Intraobserver and interobserver agreements using kappa measures were 0.42 to 0.66 and 0.43 to 0.49, respectively. Only 6% to 8% of paired intraobserver classifications differed by more than one category. Observer-specific disagreement was evident both within and between observers. A small, but significant, occasional variation was also seen. Although reliability may improve by an analysis of disagreement, it appears that the arthroscopic grading of early osteoarthritic lesions is inexact.     

正常与异常子宫内膜中Bc1-2、Bax mRNA表达

为了解正常和异常子宫内膜中 Bc1 -2和 Bax m RNA的表达及与凋亡的关系。应用原位杂交方法检测了 2 7例正常子宫内膜 ,1 2例子宫内膜增殖症和 1 0例癌变子宫内膜 Bc1 -2和 Bax m RNA的表达情况。结果 :正常子宫内膜组织腺细胞 Bc1 -2与 Bax m R-NA表达的比例与子宫内膜的周期性变化密切相关 ,Bc1 -2 m RNA表达在增殖期增强 ,分泌期减弱 ,Bax m RNA表达则相反。增殖症和癌变子宫内膜组织中 ,Bc1 -2和 Bax m RNA表达呈正相关 (rs=0 .886 ,P<0 .0 5) ,随着子宫内膜由良性增生到恶性增生 ,Bc1 -2 m R-NA表达逐渐减弱至丧失表达 ;Bax m RNA在增殖症子宫内膜中 ,随着增生的异型化 ,表达逐渐增强 ,而在癌变子宫内膜中 ,随着病理分级的降低 ,表达逐渐降低。结论 :Bc1 -2和Bax基因对于维持正常子宫内膜周期性变化的平衡起着重要作用 ,在增殖症和癌变子宫内膜中表达的异常变化可能与子宫内膜癌生物学行为和预后相关。     

A clinically applicable fracture classification for distal humeral fractures

The purpose of this study was to design a clinically applicable classification for distal humeral fractures that would provide guidance to the surgeon with regard to surgical approach and operative management. The new classification was assessed by use of the original radiographs from a study comparing distal humeral fracture classifications undertaken in Oxford, England, and was validated by use of the exact methodology of that study. Nine independent assessors were asked to classify 33 sets of radiographs on 2 separate occasions using the classifications of Riseborough and Radin, Mehne and Jupiter, and the AO, as well as the new classification system. With the use of the kappa statistic, the level of interobserver and intraobserver agreement was determined. The new classification system was found to be both substantially reliable (kappa, 0.664) and reproducible (kappa, 0.732). The new classification achieved superior interobserver and intraobserver agreement compared with the other 3 classification systems, with a low proportion of unclassifiable fractures. Used in conjunction with a management algorithm, we believe that the new classification aids the surgical decision-making process for these complex fractures.     

Histologic evaluation of the glenohumeral joint capsule after radiofrequency capsular shrinkage for atraumatic instability

We evaluated histologically 10 biopsy specimens taken preoperatively from the anterior-inferior glenohumeral ligament from patients with atraumatic instability who had undergone radiofrequency capsular shrinkage, 10 taken immediately postoperatively, and 13 taken before revision. The synovial and subsynovial layers returned to normal histology in biopsy specimens taken from 6 months onwards. Collagen bundles in the fibrous layer continued to have a reparative histology during the period of the study (up to 37 months). The type of radiofrequency probe used (monopolar or bipolar) had no effect on the histologic healing process (P > 0.5, chi2 test). A histologic score was introduced, and this was found to have an excellent intraobserver agreement (weighted kappa, 0.840) and a moderate interobserver agreement (weighted kappa, 0.698).     

Interobserver and intraobserver variation in classification systems for fractures of the distal humerus

We assessed the inter- and intraobserver variation in classification systems for fractures of the distal humerus. Three orthopaedic trauma consultants, three trauma registrars and three consultant musculoskeletal radiologists independently classified 33 sets of radiographs of such fractures on two occasions, each using three separate systems. For interobserver variation, the Riseborough and Radin system produced 'moderate' agreement (kappa = 0.513), but half of the fractures were not classifiable by this system. For the complete AO system, agreement was 'fair' (kappa = 0.343), but if only AO type and group or AO type alone was used, agreement improved to 'moderate' and 'substantial', respectively (kappa = 0.52 and 0.66). Agreement for the system of Jupiter and Mehne was 'fair' (kappa = 0.295). Similar levels of intraobserver variation were found. Systems of classification are useful in decision-making and evaluation of outcome only if there is agreement and consistency among observers. Our study casts doubt on these aspects of the systems currently available for fractures of the distal humerus.     

Malignancy is in the eye of the beholder: Pathologic diagnosis of challenging follicular neoplasms in the era of noninvasive follicular thyroid neoplasms with papillary-like nuclear features and immunohistochemical and molecular adjuncts

BackgroundClassification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts.MethodsOne representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient.ResultsAgreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%).ConclusionDespite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge.     

Core biopsies of renal tumors: a study on diagnostic accuracy, interobserver, and intraobserver variability

OBJECTIVE: The diagnostic accuracy of in-bench core biopsies (CBs) from renal masses, and the interobserver and intraobserver variability in pathological subtyping of renal tumors were assessed. METHODS: We performed two CBs in 62 consecutive renal masses suspected for renal cell carcinoma (RCC), obtained after radical or partial nephrectomy and, in one case, after autopsy. Routine hematoxylin-eosin (HE)-stained sections from each CB were evaluated by five pathologists on two occasions. The surgical specimen was the reference standard. Diagnostic accuracy and the generalized kappa for intraobserver and interobserver agreement were calculated. RESULTS: Five tumors were benign and 57 malignant. Eight percent to 16% of the CBs were considered inadequate for diagnosis. In 0-8% of the cases, the pathologist could not discriminate between a benign or malignant tumor. Overall accuracy ranged from 77% to 90%. Sensitivity (79-100%) and positive predictive value (100%) were high with narrow 95% confidence interval (95%CI). Specificity (100%) was high but negative predictive value (29%-100%) varied, with wide 95% CI. Interobserver agreement was fair to almost perfect (kappa=-0.010 to 0.830) for the different subtypes. In 64-81% of the CBs, the subtype was correctly classified. Intraobserver agreement was substantial (mean kappa=0.628) for all pathologists. CONCLUSION: Diagnostic accuracy of CBs was high, with a diagnostic yield varying between 84% and 92%. Pathological subtyping of CBs was highly reproducible with the exception of the chromophobe renal cell carcinoma, which was problematic on HE-stained sections only.