Discrepant Cases Research Articles

Whole slide images for primary diagnostics in dermatopathology: a feasibility study

BackgroundDuring the last decade, whole slide images (WSI) have been used in many areas of pathology such as teaching, research, digital archiving, teleconsultation and quality assurance testing. However, WSI have...

BRCA1/2 testing: uptake, phenocopies, and strategies to improve detection rates in initially negative families

In families with clustering of breast and ovarian cancer, molecular testing of the major susceptibility genes BRCA1/2 helps to identify patients with disease mutations and healthy persons at high risk who can participate in targeted intervention programs. We investigated 5559 families from the German Consortium for Hereditary Breast and Ovarian Cancer included between 1997 and 2008 and treated under clinical routine conditions. In each family an index patient/person had been screened for deleterious mutations in BRCA1/2. Healthy relatives agreed to predictive testing in 888 of 1520 BRCA1/2 mutation-positive families (58%). Of 2646 eligible unaffected first-degree relatives 1143 decided to be tested (43%). In 325 families with BRCA1/2-positive index patients one related BC/OC patient was tested and 39 (12.0%; 95% confidence interval: 8.7-16.0%) discrepant cases found. A second related individual was screened in 163 of 3388 (4.9%) families with BRCA1/2-negative index patient and in eight families a BRCA1/2 mutation was found. In BRCA1/2 mutation-positive families, BC/OC patients lacking the familial mutation have to be expected at a rather high rate. In families with BRCA1/2-negative index patient we recommend a second screening if another patient with a high probability of carrying a BRCA1/2 mutation is available.

Clinical impact of second opinion in thyroid fine needle aspiration cytology (FNAC): A study of 922 interinstitutional consultations

Interinstitutional consultation in pathology has shown to improve patient safety by detecting interpretive errors that may significantly impact clinical management. We conducted a study of 922 cases of thyroid FNAC slides, referred to our institution over a 2-year period, to assess the magnitude of discrepancies and determine the clinical impact of second opinion. Disagreements were categorized as none, minor or major, the latter two defined as one- or two-step deviations respectively on the NCI diagnostic categories scale. There were 122 disagreements (13%), including 44 major and 78 minor. Seventy-five patients underwent a change in management based on second opinion, in conjunction with clinical and radiologic findings (age, size of nodule, family history, ultrasonographic appearance, and solitary versus multiple nodules). The second opinion was supported on follow-up in 57% of major discrepancies, and the initial diagnosis was concurrent with the surgical diagnosis in 7% cases. The remainder (36%) of major discrepancy cases did not undergo surgery, precluding tissue confirmation. Critics have alleged increased costs due to interinstitutional consultations. However, cost avoidance from lost wages, potential surgical complications, and litigation is not easily quantified. Using a simplified calculation to objectively measure the costs associated with changed diagnoses, we estimate that second opinion of these 922 cases resulted in potential cost saving of $940,166 based on current Medicare reimbursement codes. Our study indicates the need for a quality-control program of outside thyroid FNA slides, especially in "high discrepancy categories" as discussed in the article.

578 Pet imaging standards and quality assurance for the rubidium ARMI (alternative radiopharmaceutical for myocardial imaging) multicentre trial

SPECT myocardial perfusion imaging (MPI) is typically used to assess coronary artery disease (CAD). The global shortage of Tc-99m has highlighted the need for alternate methods. 3D PET MPI with Rb-82 is considered to have superior accuracy and lower radiation dose. Rb-ARMI is a multicentre imaging trial with a preliminary goal of distributing and standardizing Rb-82 PET MPI in Canadian centres using 3D PET-CT technology. Following standardization of imaging protocols at all sites via cardiac phantom scans, low-dose (10 MBq/kg) rest and pharmacological stress Rb-82 PET MPI was performed on patients. Sum stress, rest and difference scores (SSS, SRS, SDS = SSS-SRS) were assigned using a guideline database with a 75% normal threshold and a standard color-map over 17 segment polar-map segments (4DM, INVIA). 25 initial cases from the recruiting sites were co-read at the core lab to determine scoring variability and clinical diagnosis concurrence. Scores with differences > 3 underwent a third independent review to reach consensus. To evaluate scoring consistency and improvement before and after consensus review Pearson's correlation (R) was used. The expected scores of SSS = 2, SRS = 0, SDS = 2 were achieved with the qualifying phantom scans at all imaging sites on 6 different 3D PET-CT cameras. Clinical patient scores between the core and three of the recruiting sites showed good overall agreement: R = 0.93 for SSS and 0.92 for SDS. 85% of SSS scores and 89% of SDS scores had differences (site-core) = > 3 (Fig 1A). The largest discrepancies occurred in cases with defect regions spanning multiple segments; yet, these cases were all correctly identified as abnormal. As a result of consensus review, scoring agreement improved to: R = 0.96 for SSS and 0.95 for SDS (Fig 1B). Overall, the same 51% of cases were diagnosed as abnormal by core and site reviews, demonstrating full agreement of clinical interpretation. Scoring of the Rb-82 MPI scans at the recruiting sites was found to be in good agreement with core lab standards. With consensus reading of the most discrepant cases, scoring agreement was improved demonstrating that greater consistency is achievable with increased training and experience. Cases continue to be reviewed on a monthly basis to ensure maintenance of these standards. With these imaging standards and quality assurance methods in place, Rb-82 MPI techniques can be easily disseminated with highly repeatable interpretation across imaging centers with different 3D PET-CT equipment.

Incidence of placental mosaicism leading to discrepant results between QF‐PCR and karyotyping in 22,825 chorionic villus samples

To review the frequency and analyse the origin of completely discrepant results observed between QF-PCR and karyotyping in chorionic villus samples (CVS) as a result of placental mosaicism. Also, to assess QF-PCR results for biallelic or triallelic patterns and determine their significance. Between May 2002 and December 2009, 22 825 CVS were received at TDL Genetics for processing by QF-PCR and karyotype. The QF-PCR and karyotype data were compared to determine the incidence of discrepant results. Of the 22 825 samples received, 22 779 (99.8%) gave concordant results between the PCR and karyotype, and 46 samples (0.2%) gave discordant results. Of these discrepant cases, 5 displayed triallelic peaks and 41 displayed biallelic peaks. All discordant results are due to the presence of placental mosaicism, a known limitation of using this sample type for prenatal diagnosis. This retrospective study of placental mosaicism in CVS is the largest single centre study to date and provides a figure for the occurrence of completely discrepant results between QF-PCR and karyotype due to placental mosaicism. This study also demonstrates that the presence of triallelic peaks at QF-PCR is not sufficient to exclude the presence of placental mosaicism.

Impact of chromosome 17 centromere region assessment on HER2 status reported in breast cancer

Recent studies have indicated that polysomy 17 is a rare event in breast cancer, and polysomy is usually mimicked in FISH analysis by gain or amplification of the centromere covered by the chromosome 17 centromere probe. To estimate the impact of chromosome 17 centromere assessment on routine practice, we conducted a retrospective re-classification study. Four hundred and five consecutive cases were selected. The original molecular pathology reports were available. Centromere 17 copy counts were ignored in the reassessment. Altogether, nineteen (4.69%) discrepant cases were found, from which five (1.23%) were considered originally non-amplified but had an HER2 copy number >6. Therefore, we reclassified them as HER2-amplified, while fourteen (3.46%) cases were originally considered amplified with 6 or fewer HER2 signals/cell. The discrepant cases found in our reassessment study would require further high-resolution genetic analysis to resolve the disagreement. On the other hand, our result also highlights that for the vast majority of breast cancer cases traditional FISH examination is still adequate to reach the correct diagnosis. This diagnostic gap must be filled by more sophisticated genetic examinations. Moreover, upcoming HER2 guidelines should consider the aid that high-resolution karyotyping can give to the diagnostic algorithm.

Standardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells

Recent misclassification (false negative) incidents have raised awareness concerning limitations of immunohistochemistry (IHC) in assessment of estrogen receptor (ER) in breast cancer. Here we define a new method for standardization of ER measurement and then examine both change in percentage and threshold of intensity (immunoreactivity) to assess sources for test discordance. An assay was developed to quantify ER by using a control tissue microarray (TMA) and a series of cell lines in which ER immunoreactivity was analyzed by quantitative immunoblotting in parallel with the automated quantitative analysis (AQUA) method of quantitative immunofluorescence (QIF). The assay was used to assess the ER protein expression threshold in two independent retrospective cohorts from Yale and was compared with traditional methods. Two methods of analysis showed that change in percentage of positive cells from 10% to 1% did not significantly affect the overall number of ER-positive patients. The standardized assay for ER on two Yale TMA cohorts showed that 67.9% and 82.5% of the patients were above the 2-pg/μg immunoreactivity threshold. We found 9.1% and 19.7% of the patients to be QIF-positive/IHC-negative, and 4.0% and 0.4% to be QIF-negative/IHC-positive for a total of 13.1% and 20.1% discrepant cases when compared with pathologists' judgment of threshold. Assessment of survival for both cohorts showed that patients who were QIF-positive/pathologist-negative had outcomes similar to those of patients who had positive results for both assays. Assessment of intensity threshold by using a quantitative, standardized assay on two independent cohorts suggests discordance in the 10% to 20% range with current IHC methods, in which patients with discrepant results have prognostic outcomes similar to ER-positive patients with concordant results.

Gene Expression Profiling of Duodenal Biopsies Discriminates Celiac Disease Mucosa From Normal Mucosa

Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n = 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n = 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed.

Molecular epidemiological analysis of Mycobacterium kansasii isolates

To make molecular epidemiological analysis of Mycobacterium kansasii (M. kansasii) isolates. We examined 174 M. kansasii isolates from clinical samples of patients at National Hospital Organization Kinki-chuo Chest Medical Center from June 1, 2002 to August 31, 2005 by polymerase chain reaction (PCR) -restriction analysis (PRA) of the heat shock protein (hsp) 65 gene (hsp65-PRA), sequencing (ITS, 16S-23S internal transcribed spacer, and hsp65 for discrepant case between hsp65-PRA and ITS sequence), pulsed-field gel electrophoresis (PFGE), and restriction fragment length polymorphism (RFLP) with the major polymorphic tandem repeat (MPTR) probe and the IS1652 probe of genomic DNA. Of the 174 M. kansasii isolates, 170 strains were classified as M. kansasii type I using hsp65-PRA, while two isolates belonged to type II and one each isolate to type IIb and VI, respectively. Although the ITS sequence of these isolates also identified the same region of polymorphism by hsp 65-PRA, only type II b might be revealed atypical type II, a transitional type from typical type II to intermediate type I by hsp65 sequence. The polymorphic patterns by RFLPs with MPTR and IS1652 probe were shown specific for each homogeneous cluster by hsp 65-PRA. In addition, 159 isolates were recognized the same common pattern A by PFGE analysis. In contrast, the rest 15 isolates revealed significant polymorphism within 11 isolates of type I, and 4 isolates among type II, IIb, and VI. We verified the M. kansasii genotype I was predominant, with the same pattern of major worldwide type regions, and reflected a very tight clonal structure. Type I was furthermore indicated recognition of subtypes by PFGE analysis.

First trimester fetal head and trunk volume predict growth disturbance in twin pregnancy

To evaluate the usefulness of first trimester fetal head and trunk volume (FHTV) in predicting growth disturbance in twin pregnancy. We studied 46 twin pairs from 11 and 14 weeks to delivery. There were 35 dichorionic (76%) and 11 monochorionic (24%) pregnancies. FHTV was assessed by VOCALTM. An inter-twin discrepancy in FHTV, crown-rump length (CRL) and birthweight (BW) were defined by an inter-twin difference greater than 15%. Growth retardation was defined as BW of at least one twin below the 10th percentile. There were 17 cases (37%) of FHTV discrepancy. BW discrepancy and growth retardation were more significantly frequent in cases with FHTV discrepancy than without [11/17 (64.7%) vs 4/29 (13.8%), P = 0.0004 and 7/17 (41.2%) vs 3/29 (10.3%), P = 0.02, respectively]. The detection of BW discordance and growth retardation were significantly higher when using FHTV discordance than CRL discrepancy in the first trimester [11/15 (73%) vs 2/15 (13.3%), P = 0.00001 and 7/10 (70%) vs 1/10 (10%), P = 0.0001, respectively]. FHTV discrepancy is a predictor for growth disturbance in twins.

A case of consistent discrepancies between urine and blood human chorionic gonadotropin measurements

Our laboratory was confronted with two successive urine samples from a single patient which tested positive for human chorionic gonadotropin (hCG) when tested with both qualitative and quantitative assays, combined with no detectable hCG in corresponding plasma samples. Serial dilution and recovery experiments were performed in order to investigate the presence of interfering substances or a high-dose hook effect. The ovarian cysts that were removed from this patient were immunohistochemically stained using polyclonal anti-human hCG antibodies. Furthermore, a urine sample was sent to the USA hCG Reference Service for hCG variant analysis. Dilution and recovery experiments in urine and plasma samples were unremarkable. The biopsy stained negative for human hCG and free β-subunit. hCG isoform analysis in the urine sample revealed that approximately 87.5% of the immunoreactive hCG lacked the β-subunit C-terminal peptide (CTP). We report a rare case in which two successive urine samples test positive for hCG whereas in corresponding plasma samples hCG is undetectable. The majority of the total hCG contained a degraded form of β-subunit that lacks the CTP. This hCG variant, possibly of pituitary origin, is thought to have an extreme fast clearance rate possibly explaining the discordance between the hCG results in urine and plasma samples.

10. Correlation between brain tumour frozen sections and final diagnoses at Royal North Shore Hospital

The accuracy of frozen sections performed intraoperatively is an important factor in influencing the speed and efficacy of neurosurgical operations. We examined the correlation between 159 consecutive brain frozen sections and the final histological diagnosis. 135 cases (85%) showed complete or close correlation. 24 cases (15%) showed significant discrepancy. In 11 (46%) of the discrepant cases this was due to sampling error – usually because higher grade areas were not sampled at the time of frozen section but were identified in the paraffin processed tissue. In only 7 (4% of the total cases) was discrepancy partially or totally attributed to error in interpretation of the frozen section material. These discrepant lesions comprised two cases of inflammatory change thought to be a low grade tumour, an unclassifiable sarcoma thought to be a spindled cell meningioma, a high grade malignant lesion subsequently demonstrated to be lymphoma, a glioblastoma thought to be lymphoma, a low grade glioma subsequently classified as a high grade glioma when mitoses were identified and an anaplastic oligodendroglima mimicking gliosis. We conclude that sampling error (largely out of the control of the surgical pathologist) is the main cause for discrepant frozen sections of brain. Pathologists should be aware of the potential for inflammatory change to mimic neoplasm at frozen section.

Contractual liability: In European, comparative and Serbian law

Contractual liability is an important topic of the ongoing reform of the effective Serbian Law on Obligations (2007-2009), which aims to harmonize the national legislation in this field with the laws of the European Union. In this paper the author analyzes the evolution of the traditional European civil codes (the German BGB, French Code civil, the Austrian ABGB the Swiss OR and the Hungarian Civil Code), with due attention to the doctrine and jurisprudence, taking into account the proposed reforms of the effective Serbian Law on Obligations concerning issues of contractual liability, such as the legal consequences of nonperformance, misperformance, default, etc. The author is of the opinion that the notion of the breach of contract doesn't cover all the cases in which contractual liability arises, although it embraces nonperformance, misperformance and default. The notion of contractual liability, namely, covers not only the cases of breach of contract, but the infringement of public policy, good morals and mandatory rules, which all lead to the nullity of the contract. In cases of voidable contracts (that is in case of defects of contractual will, such as mistake, deceit and duress) it is questionable whether the scope of contractual liability should be extended to mistake, which is a case of nonconscious discrepancy between contractual will and its expression. It is undisputable that contractual liability arises in case of deceit and duress, to the burden of the party acting in bad faith. The rescission of contract entails a separate complex of legal issues, since it may be justified by the other party's breach of the contract. It can also be onesided, two-sided or by a mutual agreement. Furthermore, specific rules apply to rescission of contract due to changed circumstances. In case of termination of a contract by mutual agreement, the parties usually agree on the extent of liability, that is on the extent of indemnification. Contractual liability is also specific that, according to the principle of parties' autonomy, the parties always may in advance agree on the extent of damages for the case of breach of contract, in a form of a clause on liquidated damages, forfeit money, suretyship for indemnification, the limitation of the sum insured in insurance contracts, clauses in the general conditions of business, etc. The author calls attention to the fact that these clauses in certain extent limit the scope of the indemnification for breach of a contract, according to which this liability differs from the liability for torts, where the principle of full indemnification applies as a rule.

Recurred Parathyroid Carcinoma: A Case of Cervical Recurrence Presenting Discrepancy between Image Findings and Operative Findings

Recurred Parathyroid Carcinoma: A Case of Cervical Recurrence Presenting Discrepancy between Image Findings and Operative Findings

S 領域の変異株による HBs 抗原（EIA 法）偽陰性の 1 例と HBs 抗原関連試薬反応性

The presence in serum of the Hepatitis B surface antigen (HBsAg), the outer envelope of the hepatitis B virus (HBV), indicates viral infection, used in laboratory tests to confirm this. We report a case of discrepancy among HBsAg test results detected between measurements in a subject with HB infection. Gene analysis demonstrated several S region gene mutations, not detected previously. We tested 12 measurements e.g., EIA, CLIA, CLEIA, F-EIA, MAT, and IC for whether they could detect our subject's HBsAg and found that it was not recognized by a method using only a single monoclonal antibody to detect HBsAg in two detection processes, in contrast to the 11 other measurements, which used two different antibodies. This case shows that amino acid substitution may cause a false negative result for HBsAg. Gene mutations known to occur in HBV, should thus trigger an awareness of the need to keep in mind that false negative results can happen in case such as ours.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders

To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Intra-ampullary Papillary-Tubular Neoplasm (IAPN)

There has been no uniform terminology for systematic analysis of mass-forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia) that occur specifically within the ampulla. Here, we provide a detailed analysis of these neoplasms, which we propose to refer to as intra-ampullary papillary-tubular neoplasm (IAPN). Three hundred and seventeen glandular neoplasms involving the ampulla were identified through a review of 1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms characterized by substantial preinvasive exophytic component that grew almost exclusively (>75%) within the ampulla (in the ampullary channel or intra-ampullary portions of the very distal segments of the common bile duct or pancreatic duct) were analyzed. (1) Clinical: The mean age was 64 years, male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The tumors had a mixture of both papillary and tubular growth (each constituting at least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary (GPB) based on the predominant pattern, 74% were classified as INT and 26% as GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1 89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there was an associated invasive carcinoma. Size of the tumor and amount of dysplasia correlated with the incidence of invasion. Invasive carcinoma was of INT-type in 58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component was the same as that of the preinvasive component in 84%. All discrepant cases were pancreatobiliary-type invasions, which occurred in INT-type preinvasive lesions. (5) OUTCOME: The overall survival of invasive cases were significantly worse than that of noninvasive ones (57% vs. 93%; P=0.01); and 3 years, 69% versus 100% (P=0.08); and 5 years, 45% versus 100% (P=0.07), respectively. When compared with 166 conventional invasive carcinomas of the ampullary region, invasive IAPNs had significantly better prognosis with a mean survival of 51 versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01). Tumoral intraepithelial neoplasia occurring within the ampulla are highly analogous to pancreatic or biliary intraductal papillary and tubular neoplasms as evidenced by their papillary and/or tubular growth, variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus we propose to refer to these as IAPN. IAPNs are biologically indolent; noninvasive examples show an excellent prognosis, whereas those with invasion exhibit a malignant but nevertheless significantly better prognosis than typical invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of 230) of invasive carcinomas within the ampulla arise in association with IAPNs.

Cervical cytology/histology discrepancy: a 4‐year review of patient outcome

To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80,926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high-grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow-up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post-excision. During the 4-year follow-up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow-up is essential because a small percentage of patients may have disease that has been missed.

Detection of C4d Deposition in Cardiac Allografts: A Comparative Study of Immunofluorescence and Immunoperoxidase Methods

Complement activation, evidenced by deposition of C4d, is important in the diagnosis of antibody-mediated rejection of cardiac allografts. C4d deposition can be assessed by either immunofluorescence (IF)- or immunoperoxidase (IP)-based methods. The use of methods varies considerably among institutions, but there are few data addressing their diagnostic equivalence. To compare IF and IP C4d staining on paired endomyocardial biopsy samples from a large number of heart transplant patients. Retrospectively selected paired frozen and paraffin-embedded samples from the same biopsy were stained for C4d by IF and IP methods. Capillary staining was scored by using a 0, 1+, 2+, 3+ scale. A total of 296 biopsy pairs from 70 patients were studied. There were two hundred forty-three cases that were scored 0, twenty-four scored 1+, sixteen scored 2+, and thirteen scored 3+ by IF. Two hundred thirty-one cases scored 0, forty scored 1+, ten scored 2+, and fifteen scored 3+ by IP. Complete agreement was seen in 81% of cases. Among discrepant cases, 89% (n = 51) were minor (±1) and 11% (n = 6) were major (±2). Five of the 6 major discrepancy biopsies came from 2 patients, both of whom had concordant (IF and IP) 3+ results on prior biopsies. The weighted κ value for the entire sample set was 0.78 and for the first biopsy only set (to correct for bias introduced by multiple biopsies from the same patient) the weighted κ value was 0.88. Immunofluorescence and IP C4d staining methods are highly comparable and are both viable options for antibody-mediated rejection surveillance in transplant heart biopsies.

Chasing shared understanding in drilling operations

Lack of shared understanding is frequently found to be the main cause when accidents are investigated. Still, few studies explicitly explore and document the causal effects of shared understanding in successful work. Thus, the attribution of insufficient shared understanding as an accident cause lacks the substantiation of shared understanding as a contributor to successful work. In this article a case of measurement discrepancies in an offshore drilling operation is studied, and in the elaboration of the case shared understanding is found not to qualify as a condition with significant impact on the collaborative work. One important reason for this is the epistemological inadequacy of the different concepts of shared understanding. Although more critical research on shared understanding is needed before one can conclude more generic on this topic, the findings are important to the current development of Integrated Operations where shared understanding is pointed out as an important target area.