Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate.

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor of prostatic adenocarcinoma according to virtually all available evidence. This lesion is characterized by cellular proliferations within pre-existing ducts and acini, with nuclear and nucleolar enlargements similar to those seen in prostate cancer, although unlike cancer HGPIN retains a basal-cell layer. The recognition of HGPIN is clinically important because of the strong association between this disease and prostatic carcinoma. The predictive value for cancer of an initial diagnosis of HGPIN on needle biopsy has substantially declined, with values falling from 36% to 21%. A major factor contributing to this decline is related to increased use of needle biopsy core sampling, which has provided the means for many cancers associated with HGPIN to be detected on initial biopsy; repeat biopsy, even with good sampling, does not detect many additional cancers. Other possible findings in the prostate might indicate premalignant disease (low-grade prostatic intraepithelial neoplasia, atrophy, malignancy-associated changes, and atypical adenomatous hyperplasia or adenosis), but the data for these premalignant diseases are much less convincing than those for HGPIN.