The Importance of Cytologic Intrarater and Interrater Reproducibility: the Case of Ductal Lavage

Abstract

The reproducibility of a test result is a critical component of its clinical utility. Little information is available concerning the intrarater reproducibility of cytologic assessments. This study evaluated the reproducibility of cytologic interpretation of epithelial cells obtained from ductal lavage (DL), a minimally invasive method used to obtain sample cells from breast tissue. Two cytospin slides were made for each duct sampled. Slides with <10 cells were considered inadequate to make a diagnosis; the remaining slides were classified into mildly atypical, markedly atypical, and malignant cells. Each pair of slides were classified by the more serious diagnosis. DL samples from 100 ducts were independently blind-reviewed by two experienced cytopathologists. All abnormal slides and a random sample of normal slides and slides identified as inadequate for diagnosis (n = 43) were rereviewed. The k for intrarater agreement was 0.59 F 0.10 for cytopathologist 1 and 0.33 F 0.08 for cytopathologist 2. The k for interrater agreement of slides from 100 ducts was 0.46 F 0.07. The interrater agreement of the slides that were rereviewed was k = 0.27 F 0.09. Fair to moderate intrarater and interrater agreement of DL cytology was observed. Low intrarater and interrater cytologic consistency may compromise the interpretation of clinical studies of DL. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2553 -6)

Reproducibility of ductal lavage cytology and cellularity over a six month interval in high risk women

“…Together, our findings confirm and extend previous results from smaller studies [11][12][13], and show that (1) an initial finding of mild atypia is not reproducible on second lavage at intervals ranging from 2 to 14 months, and (2) a significant minority of women (about 20%) may convert from benign cytology at baseline to mild atypia at the repeat procedure. Among other problematic issues with the use of cytologic diagnosis as a biomarker, these findings raise concerns regarding single arm trial designs, where randomized placebo controls are not included.…”

“…Because the cytologic diagnoses of benign and mild atypia have a subjective component, we included a blinded review of cytological findings by an expert reference cytopathologist (SM) in our study design. This analysis showed a higher concordance between observers (kappa statistic of 0.62) than in previous studies [13,14], possibly because of our higher threshold for sample adequacy (100 rather than 10 epithelial cells). Nevertheless, of the 51 samples with discordant results between cytopathologists (nonbolded boxes of Table 4), 31 or 60% involved discrepancies in the reading of benign and mildly atypical samples.…”

Ductal Lavage Is an Inefficient Method of Biomarker Measurement in High-Risk Women

“…Similar results were documented in a pre-mastectomy DL study 19 where mild atypia constituted one-third of samples and was the most challenging and least reproducible diagnostic category. In another study of DL reproducibility, 14/69 women entered into the study underwent two DL procedures and the reproducibility of cellularity and cytology was very similar to that observed in our study 20.…”

The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer—a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation

“…In our study, the fair cytologic reproducibility observed can be partly explained by poor intra-rater agreement (j = 0.60 F 0.11), which was subsequently identified when all abnormal slides and random samples of normal slides were re-reviewed (16). Cytologic reproducibility was low for benign, mildly atypical, and markedly atypical cells.…”