Reproducibility of the Banff schema in reporting protocol biopsies of stable renal allografts.

BACKGROUND: There is evidence that biopsy of stable renal allografts may be of value in predicting chronic allograft nephropathy, the main cause of graft loss. However, the reproducibility of such histological evaluation has not been tested in this setting. We tested the reproducibility of the Banff schema for this purpose. METHODS: We rated acute and chronic changes in 184 protocol biopsies. Individual pathologists at two different Canadian transplant centres reported independently. RESULTS: There was agreement in 73.53, 42.86, and 77.08% of cases in assigning a diagnosis of acute rejection, borderline changes (as defined in the schema), and no acute rejection, respectively. Applying kappa statistics, there was very good agreement in making the diagnosis of acute rejection vs no acute rejection (kappa 0.77). There was good inter-observer agreement in scoring glomerulitis, intimal arteritis, interstitial infiltrates, tubulitis, and arteriolar hyalinosis. Rating chronic changes also gave good inter-observer agreement (kappa=0.53, 0.65, and 0.62, respectively, for mild, moderate, and severe chronic allograft nephropathy). Agreement on transplant glomerulopathy was, however, poor. CONCLUSIONS: We conclude that the Banff classification provides a reproducible method for the histological assessment of protocol renal allograft biopsies in stable grafts. Such biopsies may be valuable in detecting subclinical rejection and early chronic allograft nephropathy and may also be used as surrogate end-points in the evaluation of therapy to prevent the latter.     

International variation in histologic grading is large,and persistent feedback does not improve reproducibility

Histologic grading systems are used to guide diagnosis, therapy, and audit on an international basis. The reproducibility of grading systems is usually tested within small groups of pathologists who have previously worked or trained together. This may underestimate the international variation of scoring systems. We therefore evaluated the reproducibility of an established system, the Banff classification of renal allograft pathology, throughout Europe. We also sought to improve reproducibility by providing individual feedback after each of 14 small groups of cases. Kappa values for all features studied were lower than any previously published, confirming that international variation is greater than interobserver variation as previously assessed. A prolonged attempt to improve reproducibility, using numeric or graphical feedback, failed to produce any detectable improvement. We then asked participants to grade selected photographs, to eliminate variation induced by pathologists viewing different areas of the slide. This produced improved kappa values only for some features. Improvement was influenced by the nature of the grade definitions. Definitions based on "area affected" by a process were not improved. The results indicate the danger of basing decisions on grading systems that may be applied very differently in different institutions.     

Use of videographic examination for analysis of efficacy of botulinum toxin in the lower limbs in children with cerebral palsy

The objective of this study was to test the interobserver and intraobserver reproducibility of videographic gait analysis in paediatric cerebral palsy patients following botulinum toxin type-A injections. Standardized videos according to gait-specific functional criteria were assessed for 1 h. For intraobserver reproducibility, 13 of 17 items showed good/moderate correlation, one mediocre and three poor correlation. For interobserver reproducibility, 12 of 17 items showed excellent, good or moderate agreement, five items showed poor agreement. Overall, 9 of 17 items showed good intraobserver or interobserver reproducibility. Mean interobserver scores for sagittal plane items were slightly lower than mean intraobserver scores (kappa=0.509 and 0.536, respectively). In conclusion, video analysis of children with cerebral palsy based on functional criteria is useful.     

Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.     

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.     

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.     

SDF-1 expression is elevated in chronic human renal allograft rejection

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.     

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.     

A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens.

This study was designed to assess intraobserver and interobserver agreement in the diagnosis of 56 endometrial specimens by five European expert gynecologic pathologists using the WHO classification and to establish which histologic features are significantly associated with each classification category. The seven categories were simple hyperplasia, complex hyperplasia, atypical hyperplasia, well-differentiated adenocarcinoma, proliferative endometria, secretory endometria, and other. Slides were reviewed twice for diagnosis, with accompanying evaluation of a checklist of histologic features. These seven categories were eventually reduced to four and three for the purposes of data analysis. The four modified diagnostic categories consisted of hyperplasia (previously simple hyperplasia and complex hyperplasia), atypical hyperplasia, well-differentiated adenocarcinoma, and cyclical endometrium (previously proliferative, secretory, and other). The three diagnostic categories consisted of hyperplasia, endometrioid neoplasia (previously atypical hyperplasia and well-differentiated adenocarcinoma), and cyclical endometrium. Intraobserver and interobserver agreement was assessed using the percentage agreement and kappa statistics. The associations among the various histologic features and diagnoses was analyzed using multiple logistic regression to identify those features that were useful for distinguishing diagnostic categories. When using seven categories, kappa values ranged from 0.53 to 0.74 (percentage agreement, 61-79%) and from 0.33 to 0.59 (percentage agreement, 43-63%) for intraobserver and interobserver agreement, respectively. When using four categories, kappa values ranged from 0.68 to 0.73 (percentage agreement, 77-80%) and from 0.39 to 0.64 (percentage agreement, 54-73%) for intraobserver and interobserver agreement, respectively. When using three categories, kappa values ranged from 0.70 to 0.83 (percentage agreement, 80-89%) and from 0.55 to 0.73 (percentage agreement, 70-82%) for intraobserver and interobserver agreement, respectively. Data were analyzed in each diagnostic category. When using four or three diagnostic categories, the mean intraobserver and interobserver agreements varied less between categories and achieved higher values, with smaller 95% confidence intervals. The mean percentage agreement was lowest for complex hyperplasia and for atypical hyperplasia. For distinguishing cyclical endometrium versus hyperplasia, the useful histologic feature was glandular crowding. For hyperplasia versus atypical hyperplasia and for hyperplasia versus endometrioid neoplasia, the useful features were nuclear enlargement, nuclear pleomorphism, vesicular chromatin, and nucleoli, but of these, only nuclear pleomorphism achieved substantial mean intraobserver and interobserver agreements. For discriminating atypical hyperplasia from well-differentiated adenocarcinoma, the only useful feature was stromal alterations, which achieved only fair mean intraobserver and interobserver agreements. In summary, in endometrial biopsy or curettage specimens, the lack of agreement in the diagnoses of complex hyperplasia and atypical hyperplasia and the lack of reproducibility in the recognition of the histologic feature of stromal alterations to differentiate atypical hyperplasia from well-differentiated adenocarcinoma suggest that the histologic classification should be simplified by including a combined category for simple and complex hyperplasia, called hyperplasia, and a combined category for atypical hyperplasia and well-differentiated adenocarcinoma, called endometrioid neoplasia. Diagnoses of hyperplasia and endometrioid neoplasia are highly reproducible between observers from different institutions. Glandular crowding is the best histologic feature to differentiate cyclical endometrium from hyperplasia, whereas nuclear pleomorphism is the reproducible cytologic feature to differentiate hyperplasia from endometrioid neoplasia.     

Excellent interobserver agreement on grading the extent of residual carcinoma after preoperative chemoradiation in esophageal and esophagogastric junction carcinoma: a reliable predictor for patient outcome

The extent of residual carcinoma in resected esophageal cancer specimens after preoperative chemoradiation is a predictor of survival according to 3 groups: P0 (0% residual carcinoma), P1 (1% to 50% residual carcinoma), and P2 (>50% residual carcinoma). However, the interobserver variation and reliability of this classification has not been evaluated among different pathologists. Histologic hematoxylin and eosin-stained slides from 60 coded cases of esophageal adenocarcinomas treated with preoperative chemoradiation followed by esophagectomy were independently reviewed by 6 pathologists from 4 different institutions for extent of residual carcinoma and ypT stage. Interobserver agreement was analyzed by kappa (kappa) statistics, and grading of extent of residual carcinoma and ypT stage based on individual and consensus gradings were correlated with patients' survival. The interobserver agreement was excellent for extent of residual carcinoma (kappa=0.84, Kendall's W=0.92; P<0.000001) and was good for ypT stage (kappa=0.71, Kendall's W=0.88; P<0.000001). Agreement was excellent for all categories of residual carcinoma: P0 (kappa=0.87), P1 (kappa=0.81), and P2 (kappa=0.85). Extent of residual carcinoma was a significant predictor for overall survival based on individual pathologist grading (all P values <0.03), and consensus grading (13 P0, 32 P1, and 15 P2), P=0.004; independent of ypT and ypN stages in multivariate analysis (P=0.02). Our results indicate that after preoperative chemoradiation in esophageal cancer there is excellent interobserver agreement among pathologists on grading extent of residual carcinoma. The extent of residual carcinoma is a reliable and reproducible predictor of survival; this grading system may allow a novel and early means of comparing outcomes after different neoadjuvant treatment regimens.     

Reliability and necessity of dynamic computerized tomography in diagnosis of atlantoaxial rotatory subluxation

Dynamic computerized tomography (DCT) has been accepted to be the standard diagnostic method of atlantoaxial rotatory subluxation (AARS) although its reliability and reproducibility has not been shown yet. The purpose of this study was to evaluate the intraobserver reproducibility and interobserver reliability of DCT. Standard DCT scans of 18 patients with acute torticollis and 12 normal subjects were examined two times in between a time interval of 1 month by three specialists and a last-year resident to define any existing AARS. The interobserver reliability kappa coefficient was -0.015 (poor) for the first examination and 0.327(fair) for the second one. The intraobserver reproducibility kappa coefficients were 0.135 (slight), -0.204 (poor), 1.00 (almost perfect), and 0.474 (moderate) respectively. It was found that DCT has a poor reliability and reproducibility in diagnosing AARS in patients with acute torticollis. Therefore, its routine use is not cost effective in patients with acute torticollis where the deformity usually resolves by a simple cervical mobilization.     

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.     

Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study

There is compelling evidence that serous tubal intraepithelial carcinoma (STIC) is a precursor of high-grade serous ovarian carcinoma. Large-scale studies are now required to determine its biological significance and clinical implication. Before conducting these studies, a reproducible classification for STIC is needed, and that is the goal of this study. This study involved 6 gynecologic pathologists from 4 academic institutions and 3 independent rounds of review. In round 1, sixty-seven lesions ranging from normal, atypical, to STICs were classified by 5 pathologists on the basis of predetermined morphologic criteria. Interobserver agreement for the diagnosis of STIC versus not STIC was fair [κ = 0.39; 95% confidence interval (CI) 0.26, 0.52], and intraobserver reproducibility ranged from fair to moderate on the basis of percentage agreement and κ. Round 2 involved testing revised criteria that incorporated morphology and immunohistochemistry (IHC) for p53 protein expression and Ki-67 labeling in 10 sets by 3 of the pathologists. The result was an improvement in interobserver agreement for the classification of STIC (κ = 0.62; 95% CI 0.18, 1.00). An algorithm was then created combining morphology and IHC for p53 and Ki-67, and reproducibility was assessed as part of round 3. In 37 lesions reviewed by 6 pathologists, substantial agreement for STIC versus no STIC was observed (κ = 0.73; 95% CI 0.58, 0.86). In conclusion, we have developed reproducible criteria for the diagnosis of STIC that incorporate morphologic and IHC markers for p53 and Ki-67. The algorithm we propose is expected to help standardize the classification of STIC for future studies.     

Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): Reproducibility of C4d Immunohistochemistry in Kidney Allografts

Detection of C4d is crucial for diagnosing antibody‐mediated‐rejection. We conducted a multicenter trial to assess the reproducibility for C4d immunohistochemistry on paraffin tissue. Unstained slides from a tissue microarray (TMA) comprising 44 kidney allograft specimens representing a full analytical spectrum for C4d were distributed to 73 institutions. Participants stained TMA slides using local protocols and evaluated their slides following the Banff C4d schema. Local staining details and evaluation scores were collected online. Stained slides were returned for centralized panel re‐evaluation. Kappa statistics were used to determine reproducibility. Poor interinstitutional reproducibility was observed (kappa 0.17), which was equally due to limitations in interobserver (kappa 0.44) and interlaboratory reproducibility (kappa 0.46). Depending on the cut‐off, reproducibility could be improved by omitting C4d grading and only considering ± calls. Heat‐induced epitope recovery (pH 6–7, 20–30 min, citrate buffer) with polyclonal antibody incubation (<1:80, >40 min) appeared as best practice. The BIFQUIT trial results indicated that C4d staining on paraffin sections varies considerably between laboratories. Refinement of the current Banff C4d scoring schema and harmonization of tissue processing and staining protocols is necessary to achieve acceptable reproducibility.     

An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome.

BACKGROUND: The Banff classification for assessment of renal allograft biopsies was introduced as a standardized international classification of renal allograft pathology and acute rejection. Subsequent debate and evaluation studies have attempted to develop and refine the classification. A recent alternative classification, known as the National Institutes of Health Collaborative Clinical Trials in Transplantation (NIH-CCTT) classification, proposed three distinct types of acute rejection. The 1997 Fourth Banff meeting appeared to move towards a consensus for describing transplant biopsies, which incorporated both approaches. Patients who received a renal allograft at the Oxford Transplant Centre were managed by a combination of protocol and clinically indicated biopsies. We have undertaken a retrospective analysis of the biopsies correlated with the clinical outcome to test the prognostic value of the original Banff (Banff 93-95) and NIH-CCTT classifications. METHODS: Three hundred and eighty-two patients received renal allografts between May 1985 and December 1989, and were immunosuppressed using a standard protocol of cyclosporine, azathioprine and steroid. Adequate 5-year follow-up data were available on 351 patients, and of these, 293 had at least one satisfactory biopsy taken between days 2 and 35 after transplantation, the latter patients forming the study group. The D2-35 biopsies taken from these patients, which were not originally reported according to the Banff classification, were re-examined and classified according to the Banff 93-95 protocols. For each patient the biopsy found to be the most severely abnormal was selected, and the Banff and NIH-CCTT grading compared with the clinical outcome. RESULTS: Seven hundred and forty-three biopsies taken from 293 patients between days 2 and 35 after transplantation were examined and the patients categorized on the basis of the 'worst' Banff grading as follows. Normal or non-rejection, 20%; borderline, 34%; acute rejection grade I (AR I), 18%; AR IIA, 6%; AR IIB, 14%; AR III, 1%; AR IIIC, 3%; widespread necrosis 3%. The clinical outcome for the last two groups combined was very poor with 18% of grafts functioning at 3 months and 6% at 5 years. The other groups with vascular rejection (AR IIB and AR III) had an intermediate outcome, graft survival being 78% at 3 months and 61% at 5 years. The remaining four groups (normal, borderline, cellular AR I and AR IIA) had the best outcome: graft survival 95% at 3 months and 78% at 5 years with virtually no difference between the four groups. Three forms of acute rejection, namely tubulo-interstitial, vascular and transmural vascular, were identified, but only the latter two categories were associated with a poor outcome. CONCLUSIONS: The eight sub-categories of the Banff classification of renal allograft biopsies are associated with three different prognoses with respect to graft survival in the medium term. These three prognostic groups correspond to the three NIH-CCTT types. The data provide support for the consensus developed at Banff 97 separating tubulo-interstitial, vascular and transmural vascular rejection (types I, II and III acute rejection).     

Observer agreement in the scoring of the activity and chronicity indexes of lupus nephritis

The present study was designed to evaluate the observer reliability in the scoring of the activity and chronicity indexes, among three experienced pathologists, in renal biopsies from lupus nephritis (LN). Twenty-five renal biopsies of LN, were evaluated independently by three pathologists to assess the interobserver variability. For the intraobserver agreement, 5 biopsies were evaluated twice by each pathologist. The interobserver agreement for the scoring of the activity and chronicity indexes was 0.81 and 0.86, respectively. In the intraobserver agreement the same results were: for the pathologist 1, 0.95 and 0.70; for the pathologist 2, 0.91 and 0.55; for the pathologist 3, 0.89 and 0.82. In conclusion the agreement for the scoring of the activity and chronicity indexes in biopsies from LN was excellent.     

A method to reduce variability in scoring antibody‐mediated rejection in renal allografts: implications for clinical trials – a retrospective study

Poor reproducibility in scoring antibody‐mediated rejection (ABMR) using the Banff criteria might limit the use of histology in clinical trials. We evaluated the reproducibility of Banff scoring of 67 biopsies by six renal pathologists at three institutions. Agreement by any two pathologists was poor: 44.8–65.7% for glomerulitis, 44.8–67.2% for peritubular capillaritis, and 53.7–80.6% for chronic glomerulopathy (cg). All pathologists agreed on cg0 (n = 20) and cg3 (n = 9) cases, however, many disagreed on scores of cg1 or cg2. The range for the incidence of composite diagnoses by individual pathologists was: 16.4–22.4% for no ABMR; 17.9–47.8% for active ABMR; and 35.8–59.7% for chronic, active antibody‐mediated rejection (cABMR). A “majority rules” approach was then tested in which the scores of three pathologists were used to reach an agreement. This increased consensus both for individual scores (ex. 67.2–77.6% for cg) and for composite diagnoses (ex. 74.6–86.6% cABMR). Modeling using these results showed that differences in individual scoring could affect the outcome assessment in a mock study of cABMR. We conclude that the Banff schema has high variability and a majority rules approach could be used to adjudicate differences between pathologists and reduce variability in scoring in clinical trials.     

Interobserver variability in the pathological assessment of malignant colorectal polyps

BACKGROUND: Treatment of patients with malignant large bowel polyps is highly dependent on pathological evaluation. The aim of this study was to evaluate interobserver variability in the pathological assessment of endoscopically removed polyps. METHODS: The records of 88 patients with colorectal cancer who underwent endoscopic removal of malignant polyps were reviewed. Study investigators reviewed the initial pathology report; three experienced gastrointestinal pathologists reviewed all slides in a blinded fashion. Interobserver variability of pathological assessment of malignant polyps was analysed by kappa statistics. RESULTS: Seventy-six (86 per cent) of the 88 patients had malignant polyps and 12 (14 per cent) had carcinoma in situ. Agreement between experienced pathologists was substantial with regard to T stage (kappa = 0.725), resection margin status (kappa = 0.668) and Haggitt's classification (kappa = 0.682), but comparison of initial and experienced pathologists' assessment demonstrated only moderate agreement in these areas (kappa = 0.516, kappa = 0.555 and kappa = 0.578 respectively). Agreement between even experienced pathologists was poor with respect to histological grade of differentiated adenocarcinomas (kappa = 0.163) and angiolymphatic vessel invasion (kappa = - 0.017). CONCLUSION: Pathological assessment of malignant polyps varies between observers. Specialist pathologists appear to have a higher degree of consensus among themselves than with generalist pathologists with respect to T stage. The high interobserver variability with regard to histological grade of differentiated tumours is clinically irrelevant. However, variability in the assessment of angiolymphatic vessel invasion limits the value of this measurement for clinical decision making.     

Reliability and agreement between fine-cut CT scans and plain radiography in the evaluation of posterolateral fusions.

BACKGROUND CONTEXT: Current imaging techniques used to evaluate fusion status after a posterolateral fusion such as radiographs, computed axial tomography (CT) scans, and tomograms are known to be inaccurate, with error rates estimated from 20% to 40%. Previous studies evaluated CT scans using 2-4-mm thick slices with limited reconstructions. PURPOSE: The purpose of this study is to determine the intraobserver and interobserver agreement of plain radiographs and fine-cut (1-mm) CT scans with sagittal and coronal reconstructions in evaluating fusion status after instrumented posterolateral fusions. The correlation between radiographic evaluations and CT scan evaluations was also analyzed. STUDY DESIGN/SETTING: Cross-sectional, blinded. PATIENT SAMPLE: One-year radiographs and CT scans of 86 patients who had single-level instrumented posterolateral fusions. OUTCOME MEASURES: Fusion grades based on previously published criteria were determined. METHODS: Three spine surgeons graded the fusions of 86 patients who had single-level instrumented posterolateral fusions using 1-year postoperative flexion/extension lateral and anteroposterior radiographs, and fine-cut CT scans with sagittal and coronal reconstructions. The technique used to obtain the radiographs and the CT scans was the same in all cases. Two separate readings, 2 weeks apart, were done on each patient by each surgeon. The kappa coefficients for interobserver and intraobserver variability were determined. RESULTS: The intraobserver agreement using CT scans to assess fusion status was moderate for both classification systems (Molinari=0.48, Glassman 0.47). The intraobserver agreement using X-rays to assess fusion status was fair for the Molinari classification (kappa=0.37) and moderate for the Glassman classification (kappa=0.43). The interobserver agreement using CT scans to assess fusion status was moderate for both classification systems (Molinari=0.48, Glassman 0.48). The interobserver agreement using X-rays to assess fusion status was fair for both classification systems (Molinari=0.24, Glassman 0.26). Observers agreed most often when the fusion was assessed as solid (Molinari k=0.61, Glassman k=0.63). The rating on the radiographs and CT scans agreed only 46% to 59% of the time. CONCLUSIONS: Fine-cut CT scans with reconstructions have a considerably greater degree of interobserver and intraobserver agreement compared with flexion/extension and anteroposterior radiographs. Observers agree most often when the fusion is assessed as solid. Fusion evaluation based on radiographs agrees with CT scans only half the time. Future studies are needed to correlate the findings on fine-cut CT scans with surgical exploration.