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

Abstract

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.

Key Points

  • An enormous amount of knowledge, which indicates that high-grade prostatic intraepithelial neoplasia (HGPIN) might represent a heterogeneous group of lesions, has been gathered in a variety of intraductal and intra-acinar proliferations

  • Evidence indicating that HGPIN is related more closely to prostate cancer than to benign epithelium has been obtained from morphological, immunohistochemical, morphometric, molecular and genetic studies

  • The predictive value for cancer after an initial diagnosis of HGPIN on needle biopsy has substantially declined, mainly because of the increased use of needle biopsy core sampling

  • Findings other than HGPIN in the prostate might indicate premalignant disease, but the data for these are much less convincing than those for HGPIN

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Figure 1: Morphological spectrum for normal prostate to high-grade prostatic intraepithelial neoplasia
Figure 2: High-grade prostatic intraepithelial neoplasia with neuroendocrine differentiation
Figure 3: Atypical basal-cell hyperplasia (adenosis)
Figure 4: Adenocarcinoma originating from high-grade prostatic intraepithelial neoplasia
Figure 5: The effect of androgen ablation on high-grade prostatic intraepithelial neoplasia
Figure 6: Focal atrophy with high-grade prostatic intraepithelial neoplasia and adenocarcinoma

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Correspondence to Rodolfo Montironi.

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Montironi, R., Mazzucchelli, R., Lopez-Beltran, A. et al. Mechanisms of Disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate. Nat Rev Urol 4, 321–332 (2007). https://doi.org/10.1038/ncpuro0815

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