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PRECURSOR LESIONS IN PROSTATE CANCER

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High-grade prostatic intraepithelial neoplasia (PIN) is known to have a high predictive value for prostate cancer. In addition, about 2% of contemporary needle biopsies contain collections of small acini that are suspicious for cancer but which fall below the diagnostic threshold and are reported as atypical small acinar proliferation suspicious for but not diagnostic of malignancy (ASAP). Identification of PIN, ASAP or both in a needle biopsy warrants repeat biopsy for concurrent or subsequent cancer. Prostate cancer has been identified in about 50% of subsequent biopsies for PIN and up to 60% for ASAP, but most early reports were based on quadrant or sextant biopsies. Recent studies with octant or more biopsies have shown that the predictive accuracy for cancer is lower for PIN and ASAP, particularly in highly screened patient populations when compared with previously reported unscreened populations. However, both PIN and ASAP are still significant predictors of cancer compared with historic controls, and their identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma.

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PIN and ASAP can occur together in the same biopsy set without concomitant cancer. We refer to the coexistence of the two lesions in the same high-power microscopic field as ‘PIN + ASAP’. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

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HIGH-GRADE PIN

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High-grade PIN is the earliest accepted stage in carcinogenesis, possessing most of the phenotypic, biochemical and genetic changes of cancer without invasion into the fibromuscular stroma [1–6]. PIN is defined as an abnormal epithelial proliferation within pre-existing ducts and ductules, with nucleolomegaly involving at least 10% of the cells [7–9]. The term ‘PIN’ is usually used today as a synonym for high-grade PIN (formerly PIN 2 and 3 on a 1–3 scale). The high level of interobserver variability and apparent lack of predictive value with low-grade PIN limits its clinical utility [10], and most pathologists do not routinely report this finding except in research studies. Thus, PIN is now used interchangeably with high-grade PIN by most investigators. Interobserver agreement for high-grade PIN is ‘good to excellent’ [10–12]. Terms such as dysplasia, malignant transformation, carcinoma in situ and intraductal carcinoma are discouraged [13].

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EPIDEMIOLOGY OF PIN

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In the USA, an estimated 1 300 000 prostate biopsies are performed annually. Annually, around 27 350 Americans die of prostate cancer and 234 460 new cases are diagnosed [14]. The mean incidence of isolated high-grade PIN is 9% (range 4–16%) of prostate biopsies [15, 16]. This is similar to our personal experience in Richmond, Virginia, where, in 2005, 115000 new cases of high-grade PIN without cancer were diagnosed.

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The incidence and extent of PIN increases with patient age [17–20]. An autopsy study ...

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