Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies

Pathologists are increasingly exposed to prostate biopsies with small atypical foci, requiring differentiation between adenocarcinoma, atypical small acinar proliferation suspicious for malignancy, and a benign diagnosis. We studied the level of agreement for such atypical foci among experts in urologic pathology and all-round reference pathologists of the European Randomized Screening study of Prostate Cancer (ERSPC). For this purpose, we retrieved 20 prostate biopsies with small (most <1 mm) atypical foci. Hematoxylin and eosin-stained slides, including 10 immunostained slides were digitalized for virtual microscopy. The lesional area was not marked. Five experts and 7 ERSPC pathologists examined the cases. Multirater kappa statistics was applied to determine agreement and significant differences between experts and ERSPC pathologists. The kappa value of experts (0.39; confidence interval, 0.29-0.49) was significantly higher than that of ERSPC pathologists (0.21; confidence interval, 0.14-0.27). Full (100%) agreement was reached by the 5 experts for 7 of 20 biopsies. Experts and ERSPC pathologists rendered diagnoses ranging from benign to adenocarcinoma on the same biopsy in 5 and 9 biopsies, respectively. Most of these lesions comprised between 2 and 5 atypical glands. The experts diagnosed adenocarcinoma (49%) more often than the ERSPC pathologists (32%) (P<0.001). As agreement was particularly poor for foci comprising <6 glands, we would encourage pathologists to obtain intercollegial consultation of a specialized pathologist for these lesions before a carcinoma diagnosis, whereas clinicians may consider to perform staging biopsies before engaging on deferred or definite therapy.