Three‐dimensional architecture of common benign and pre‐cancerous prostate epithelial lesions

Abstract

Aim

Many glandular lesions can mimic prostate cancer microscopically including atrophic glands, adenosis and prostate intraepithelial neoplasia. While the characteristic histopathological and immunohistochemical features of these lesions have been well established, little is known about their three‐dimensional architecture. Our objective was to evaluate the three‐dimensional organization of common prostate epithelial lesions.

Methods and results

Five hundred micron thick punches (n=42) were taken from radical prostatectomy specimens, and stained with antibodies targeting Keratin 8‐18 and Keratin 5 for identification of luminal and basal cells respectively. Tissue samples were optically cleared in benzyl alcohol: benzyl benzoate and imaged using a confocal laser scanning microscope. The three‐dimensional architecture of peripheral and transition zone glands was acinar, composed of interconnecting and blind‐ending saccular tubules. In simple atrophy, partial atrophy and post‐atrophic hyperplasia, the acinar structure was attenuated with branching blind‐ending tubules from parental tubular structures. Three‐dimensional imaging revealed a novel variant of prostate atrophy characterized by large Golgi‐like atrophic spaces parallel to the prostate surface, which were represented by thin, elongated tubular structures on HE slides. Adenosis on the other hand lacked acinar organization, so that it closely mimicked low‐grade prostate cancer. High‐grade prostate intraepithelial neoplasia displayed prominent papillary intra‐luminal protrusions but retained an acinar organization, whereas intraductal carcinoma predominantly consisted of cribriform proliferations with either spheroid, ellipsoid or complex interconnecting lumens.

Conclusions

While various prostate epithelial lesions might mimic malignancy on HE slides, their three‐dimensional architecture is acinar and clearly different from the tubular structure of prostate cancer, with adenosis as exception.

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