High-grade prostatic intraepithelial neoplasia (PIN) is accepted as a premalignant lesion that has the potential to progress to prostate adenocarcinoma.1-16 Prostatic intraepithelial neoplasia is the abnormal proliferation within the prostatic ducts of premalignant foci of cellular dysplasia and carcinoma in situ without stromal invasion (Fig. 4.1).1719 The diagnostic term 'prostatic intraepithelial neoplasia' has been endorsed at multiple multidisciplinary and pathology consensus meetings,5'13'15'20-25 and the interobserver agreement between pathologists has been determined to be 'good to excellent'26'27 for high-grade PIN.

Prostatic intraepithelial neoplasia is graded from 1 to 3. Grade 1 is defined as low-grade PIN, whereas grades 2 and 3 are currently considered together as high-grade PIN; currently, conventional use of the term 'PIN' without qualification refers to only high-grade PIN. High-grade PIN is a standard diagnosis that must be included as part of the reported pathologic evaluation of prostate biopsies' transurethral resected prostate chips and radical prostatectomy specimens.15'22'24

In the USA' approximately 1 300 000 prostate biopsies are performed annually to detect 198 500 new cases of prostate cancer.28 The incidence of high-grade PIN averages 9% (range 4-16%) of prostate biopsies representing 115 000 new cases of high-grade PIN without cancer diagnosed each year.29 Highgrade PIN is the earliest accepted stage in carcinogenesis' possessing most of the phenotypic' biochemical and genetic changes of cancer without invasion of the basement membrane of the acini (Fig. 4.2).30

A role for high-grade PIN in the development of prostate adenocarcinoma is based on the fact that the prevalence of

*To whom correspondence should be addressed.

both high-grade PIN and prostate cancer increases with patient age' and that high-grade PIN precedes the onset of prostate cancer by less than one decade (Table 4.1).31-34 The severity and frequency of high-grade PIN in prostates with histological cancer is greatly increased (73% of 731 specimens) when compared to prostates without cancer (32% of 876 specimens).35-38 When high-grade PIN is found on needle biopsy' there is a 50% risk of finding carcinoma on subsequent biopsies over 3 years.24 There is also convincing evidence to suggest that high-grade PIN may represent a precursor to a more aggressive form of prostate cancer phenotype than to those that are more likely to remain indolent.9'39'40

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