Prostatic intraepithelial neoplasia

Prostatic intraepithelial neoplasia (PIN) is a microscopic lesion in the prostate which is thought to be a precursor to prostate cancer. It is often found in tissue samples or operation specimens of the prostate. PIN itself does not invade the surrounding tissue, neither does it form a tumor mass or cause any symptoms. PIN may disappear, remain unchanged, or progress to prostate cancer, often over as many as ten years. The magnitude of the risk for prostate cancer in men with PIN and the optimal follow-up stategy remain controversial.

Diagnosis

PIN is frequently found by pathologists in tissue samples from needle biopsies taken via the rectum, or in surgically removed prostate tissue. PIN can be found after transurethral surgery for benign prostatic hyperplasia (the increase in size of the prostate in middle-aged and elderly men), or after complete removal for prostate cancer (a procedure called radical prostatectomy). Blood tests for prostate specific antigen, digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are "not" useful for diagnosing PIN.

Histopathology

Microscopically, PIN is a collection of irregular, atypical epithelial cells. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer appearance. They remain fully contained within a prostate acinus (the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry for cytokeratins) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In PIN, the basal cell layer is disrupted but present.

PIN can be subdivided into different stages, based on the level of cell atypia. PIN was formerly classified as PIN 1, 2 or 3, in order of increasing cell irregularities. Nowadays, PIN 1 is referred to as low grade PIN, and PIN 2 and PIN 3 are grouped together as high grade PIN.cite journal |author=Montironi R, Mazzucchelli R, Algaba F, Lopez-Beltran A |title=Morphological identification of the patterns of prostatic intraepithelial neoplasia and their importance |journal=J. Clin. Pathol. |volume=53 |issue=9 |pages=655–65 |year=2000 |month=September |pmid=11041054 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=11041054] Only high grade PIN has been shown to be a risk factor for prostate cancer. Because low grade PIN has no significance and does not require repeat biopsies or treatment, it is not mentioned in pathology reports. As such, PIN has become synonymous with high grade PIN.

Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ (localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.

Several architectural variants of PIN have been described, and many cases have multiple patterns. The main ones are tufting, micropapillary, cribriform, and flat. Although these different appearances may cause confusion with other conditions, they have not been found to be of clinical importance. Rarer types are signet-ring-cell, small-cell-neuroendocrine, mucinous, foamy, inverted, and with squamous differentiation.

Relation to prostate cancer

There are several reasons why PIN is the most likely prostate cancer precursor.cite journal |author=Montironi R, Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M |title=Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate |journal=Nat Clin Pract Urol |volume=4 |issue=6 |pages=321–32 |year=2007 |month=June |pmid=17551536 |doi=10.1038/ncpuro0815 |url=http://dx.doi.org/10.1038/ncpuro0815] PIN is more common in men with prostate cancer. High grade PIN can be found in 85 to 100% of radical prostatectomy specimens,cite journal |author=Godoy G, Taneja SS |title=Contemporary clinical management of isolated high-grade prostatic intraepithelial neoplasia |journal=Prostate Cancer Prostatic Dis. |volume=11 |issue=1 |pages=20–31 |year=2008 |pmid=17909565 |doi=10.1038/sj.pcan.4501014 |url=http://dx.doi.org/10.1038/sj.pcan.4501014] nearby or even in connection with prostate cancer. It tends to occur in the peripheral zone of the prostate. With age, it becomes increasingly multifocal, like prostate cancer. Molecular analysis has shown that high grade PIN and prostate cancer share many genetic abnormalities.cite journal |author=Hughes C, Murphy A, Martin C, Sheils O, O'Leary J |title=Molecular pathology of prostate cancer |journal=J. Clin. Pathol. |volume=58 |issue=7 |pages=673–84 |year=2005 |month=July |pmid=15976331 |doi=10.1136/jcp.2002.003954 |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=15976331] This has been confirmed in a transgenic mouse model.

The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies).cite journal |author=Montironi R, Mazzucchelli R, Lopez-Beltran A, Cheng L, Scarpelli M |title=Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other proposed preneoplastic lesions in the prostate |journal=Nat Clin Pract Urol |volume=4 |issue=6 |pages=321–32 |year=2007 |month=June |pmid=17551536 |doi=10.1038/ncpuro0815 |url=http://dx.doi.org/10.1038/ncpuro0815]

Treatment

PIN does not require specific therapy, but close follow-up with additional biopsies is warranted. The exact timing of repeat biopsies remains an area of controversy. Studies are ongoing to evaluate the usefulness of diet modification, supplements or hormonal therapy for high grade PIN.

References

*cite journal |author=Godoy G, Taneja SS |title=Contemporary clinical management of isolated high-grade prostatic intraepithelial neoplasia |journal=Prostate Cancer Prostatic Dis. |volume=11 |issue=1 |pages=20–31 |year=2008 |pmid=17909565 |doi=10.1038/sj.pcan.4501014 |url=http://dx.doi.org/10.1038/sj.pcan.4501014
*cite journal |author=Bostwick DG, Qian J |title=High-grade prostatic intraepithelial neoplasia |journal=Mod. Pathol. |volume=17 |issue=3 |pages=360–79 |year=2004 |month=March |pmid=14739906 |doi=10.1038/modpathol.3800053 |url=http://dx.doi.org/10.1038/modpathol.3800053

Footnotes