Preneoplastic lesions of the prostate

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.