- Human pathology

Home > E. Pathology by systems > Reproductive system > Male genital system > Prostate > high-grade prostatic intraepithelial neoplasia

high-grade prostatic intraepithelial neoplasia

Sunday 12 February 2012

high grade prostatic intraepithelial neoplasia (HGPIN)

Based on few recent autopsy studies that included HGPIN in their analysis, it appears that similar to prostate cancer, HGPIN can be detected microscopically in young males, its prevalence increases with age and HGPIN shows strong association with cancer in terms of coincidence in the same gland and in its spatial distribution.

In a contemporary autopsy series of 652 prostates with high proportion of young men, Sakr et al. identified HGPIN in 7, 26, 46, 72, 75 and 91% of African Americans between the third and eighth decades compared to: 8, 23, 29, 49, 53 and 67% for Caucasian men.

In addition to higher the prevalence, this study also suggested a more extensive HGPIN in younger African American men compared to Caucasians.

In an autopsy series of 180 African and White-Brazilian men older than 40, more extensive and diffuse HGPIN in African Brazilians tended to appear at a younger age compared to Whites.

Prevalence of HGPIN in surgical prostate samples

Biopsy specimens

There are significant variations in the reported prevalence of HGPIN in needle biopsies of the prostate. This is likely to result from several reasons:
– Population studied (ethnicity, extent of screening/early detection activities).
– Observers variability as there is an inherent degree of subjectivity in applying diagnostic criteria and in setting the threshold for establishing diagnosis.
– The technical quality of the material evaluated (fixation, section thickness and staining quality).
– The extent of sampling (i.e., number of core biopsies obtained).
The majority of large recent series, have reported a prevalence of 4-6%.

The European and the Japanese literature indicate a slightly lower prevalence of HGPIN on needle biopsies.

TURP specimens

The incidence of HGPIN in transurethral resection of the prostate is relatively uncommon with two studies reporting a rate of 2.3% and 2.8%, respectively.

HGPIN in radical prostatectomy/cystoprostatectomy specimens

The prevalence of HGPIN in radical prostatectomy specimens is remarkably high reflecting the strong association between the lesion and prostate cancer.

Investigators have found HGPIN in 85-100% of radical prostatectomy specimens. In a series of 100 cystoprostatectomy specimens, Troncoso et al. found 49% and 61% of the prostates to harbour HGPIN and carcinoma, respectively.

In 48 men who underwent cystoprostatectomy for reasons other than prostate cancer, Wiley et al. found 83% and 46% of the prostates to contain HGPIN and incidental carcinoma, respectively.

More extensive HGPIN predicted significantly for the presence of prostate cancer in this study.

Morphological relationship of HGPIN to prostate carcinoma

The associations of HGPIN and prostate cancer are several:
– The incidence and extent of both lesions increase with patient age.
– There is an increased frequency, severity and extent of HGPIN in prostate with cancer.
– Both HGPIN and cancer are multifocal with a predominant peripheral zone distribution.
– Histological transition from HGPIN to cancer has been described.
– High-grade PIN shares molecular genetics features with cancer.

HGPIN is more strongly associated with intermediate-high grade prostatic carcinoma.

There is limited data addressing the relationship between the presence and extent of HGPIN in the prostate and the pathologic stage of prostate cancer. It has been reported that the total volume of HGPIN
increases with increasing pathologic stage with a significant correlation between volume of HGPIN and the number of lymph node metastases.

Molecular genetic associations of HGPIN and prostate cancer

There is extensive literature indicating that HGPIN demonstrates a range of genetic abnormalities and biomarker expression profile that is more closely related to prostate cancer than to benign prostatic epithelium.

These studies investigated aspects ranging from cell proliferation and death, histomorphometric analysis and a host of genetic alterations, inactivation of tumour suppressor genes or overexpression of oncogenes.

Clinical features

HGPIN does not result in any abnormalities on digital rectal examination. HGPIN may appear indistinguishable from cancer, manifesting as a hypoechoic lesion on transrectal ultrasound examination.

HGPIN by itself does not appear to elevate serum PSA levels.


- Webpathology


- Initial high-grade prostatic intraepithelial neoplasia with carcinoma on subsequent prostate needle biopsy: findings at radical prostatectomy. Al-Hussain TO, Epstein JI. Am J Surg Pathol. 2011 Aug;35(8):1165-7. PMID: 21716083

- Tavora F, Epstein JI. High-grade prostatic intraepithelial neoplasialike ductal adenocarcinoma of the prostate: a clinicopathologic study of 28 cases. Am J Surg Pathol. 2008 Jul;32(7):1060-7. PMID: 18496142

- Bishara T, Ramnani DM, Epstein JI. High-grade Prostatic Intraepithelial Neoplasia on Needle Biopsy: Risk of Cancer on Repeat Biopsy Related to Number of Involved Cores and Morphologic Pattern. Am J Surg Pathol. 2004 May;28(5):629-633. PMID: 15105651