Interobserver agreement and reproducibility in classification of invasive breast carcinoma: an NCI breast cancer family registry study

Abstract

Registry of this type; over 37 724 individuals have been enrolled to date. One activity of this Registry is the semicentralized pathologic review of tumors from all probands. Given the semicentralized nature of the review, this study was undertaken to determine the reproducibility, source(s) of classification discrepancies and stratagems to circumvent discrepancies for histologic subtyping and grading of invasive breast cancer among the reviewing pathologists. A total of 13 pathologists reviewed 35 invasive breast cancers and classified them by primary and secondary histologic type, Nottingham grade and score. Lymph-vascular space invasion, circumscribed margins, syncytial growth and lymphocytic infiltrate were also evaluated. A training session using a separate set of slides was conducted prior to the study. General agreement, in terms of categoryspecific j's and percent agreement, and accuracy of classification relative to a reference standard were determined. Classification of histologic subtype was most consistent (and accurate) for mucinous carcinoma (j ¼ 1.0), followed by tubular (j ¼ 0.8) and lobular subtypes (j ¼ 0.8). Classification of medullary subtype was moderate (j ¼ 0.4), but additional evaluation of degree of lymphocytic infiltrate, syncytial growth and circumscribed margins identified most cases. Category-specific j's were moderate to good for Nottingham grade (j ¼ 0.5-0.7), with the greatest agreement obtained in categorizing grade I (j ¼ 0.7), and grade III tumors (j ¼ 0.7). A flexible classification strategy that employs individual and combined criteria provides good interobserver agreement for invasive breast cancers with uniform, unambiguous histology and compensates for classification discrepancies in the more histologically ambiguous or heterogeneous cancers. Keywords: interobserver reproducibility; invasive breast cancer; familial breast cancer; breast/ovarian cancer family registryThe reproducibility of the classification and grading of invasive breast cancer and the cause(s) of interobserver disagreement among pathologists have not been adequately evaluated. Prior studies evaluating interobserver concordance in categorizing breast lesions have documented improved diagnostic agreement when the pathologists involved used agreed-upon criteria, 1 but other potential sources of poor interobserver agreement, such as the difficulties in the application of the individual histologic criteria, the individual pathologist's variation in use of these criteria, and most importantly, the ambiguous or borderline and heterogeneous nature of the

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

“…However, in their study, a prior training session was performed for the pathologists to standardize the evaluation, which was not done in our study. Our results are in line with the published data and show that the interobserver agreement for ILC is moderate [34,35]. Hormone-receptor status and grade were used to further distinguish between more aggressive ILCs (i.e.…”

“…In a study by Kiaer et al the kappa value for ILC versus invasive ductal carcinoma between each central pathology and the country as a whole was 0.3 for a cohort of 379 breast carcinomas. Longacre et al [34] showed in a cohort of N = 35 cases (including five lobular carcinomas) from a cancer registry that the accuracy for diagnosis of lobular carcinoma (comparing local assessment with reference pathology) had a mean of 90 % and a kappa value of 0.8. However, in their study, a prior training session was performed for the pathologists to standardize the evaluation, which was not done in our study.…”

The Use of Immunohistochemistry for Biomarker Assessment—Can It Compete with Other Technologies?

“…(Mengel et al 2002, 296) There is a body of literature in which the agreement among pathologists (or lack thereof) has been assessed, generally with kappa coefficients in the moderate to substantial ranges, only a few of which are cited (Coco et al 2011;Dalton, Page, and Dupont 1994;Engers 2007;Farmer, Gonin, and Hanna 1996;Foucar 1998Foucar , 2005Longacre et al 2006;McCluggage et al 2011;Mongomery 2005;Sloane et al 1999;van den Bent 2010). Fortunately, when specific criteria for diagnoses or grading are clearly defined, there is less interobserver variability (Carlson et al 1998;Komaki, Sano, and Tangoku 2006;Letourneux et al 2006;Longacre et al 2006;Rugge et al 2002). In short, there is little evidence that the ''art of pathology'' improves diagnostic accuracy, but there is considerable evidence that well-defined objective and quantifiable criteria for disease diagnosis or tumor grading improves the reproducibility of morphologic assessment.…”

Invasive lobular breast cancer. Prognostic significance of histological malignancy grading

“…The reported kappa values differ, depending on the pathologists experience in breast pathology [24]. In our study most of the tumours were evaluated by one pathologist, we do not regard this as a disadvantage.…”