False-negative Prostate Needle Biopsies: Frequency, Histopathologic Features, and Follow-up

Little is known about the frequency, histopathologic characteristics, and clinical consequences of false-negative prostate biopsies, that is, biopsies classified as benign but containing adenocarcinoma or atypical suspicious glands atypical small acinar proliferations (ASAP). Objective of this study was to evaluate false-negative prostate biopsy in a prostate cancer screening setting. Prostate biopsy sets of 196 participants of a screening trial, which had been reported as "benign" at initial diagnosis, followed by a diagnosis of adenocarcinoma in a subsequent screening round were reviewed by 2 urologic pathologists. Adenocarcinoma was identified in 19 biopsy cores corresponding to 16 (8.2%) patients and ASAP in 24 cores, corresponding to 19 patients (9.7%). All missed prostate cancers were Gleason score 6 (3+3). After correction for patient selection, the overall false-negative biopsy rate was estimated to be 2.4%; 1.1% for prostate cancer; and 1.3% for ASAP. Clinicopathologic features at the time of initial biopsy and of subsequent prostate cancer diagnosis did not differ between patients with a false-negative or true benign biopsy. Relatively low number of atypical glands (<10 glands), intense intermingling with preexistent glands or lack of architectural disorganization were the most prominent risk factors for a false-negative diagnosis. Another potential pitfall was the presence of prostate cancer variants, as 1 adenocarcinoma was of foamy gland type and 3 of pseudohyperplastic type. Routine examination of at least 1 level of prostate biopsy sets at high magnification and awareness of histologic prostate cancer variants might reduce the risk of missing or misinterpreting a relevant lesion at prostate biopsy evaluation.