High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: Current level of risk in screening population

doi:10.1016/j.urology.2004.10.010

Urology

Volume 65, Issue 3, March 2005, Pages 538-542

https://doi.org/10.1016/j.urology.2004.10.010 Get rights and content

Abstract

Objectives

To assess the current incidence of prostate carcinoma detection in serial biopsies in a prostate-specific antigen-based screening population after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia (HG-PIN) in needle biopsy tissue.

Methods

We retrospectively identified 190 men with a diagnosis of isolated HG-PIN in needle biopsy tissue. Most men (86%) were diagnosed from 1996 to 2000. Logistic regression analysis was used to predict the presence of carcinoma in these 190 men and in a control group of 1677 men with only benign prostatic tissue in needle biopsy tissue.

Results

The cumulative risk of detection of carcinoma on serial sextant follow-up biopsies was 30.5% for those with isolated HG-PIN compared with 26.2% for the control group (P = 0.2). Patient age (P = 0.03) and serum prostate-specific antigen level (P = 0.02) were significantly linked to the risk of cancer detection, but suspicious digital rectal examination findings (P = 0.1), the presence of HG-PIN (P = 0.2), and the histologic attributes of PIN were not (all with nonsignificant P values). HG-PIN found on the first repeat biopsy was associated with a 41% risk of subsequent detection of carcinoma compared with an 18% risk if benign prostatic tissue was found on the first repeat biopsy (P = 0.01).

Conclusions

The results of our study have shown that the current level of risk for the detection of prostate carcinoma in a screened population is 30.5% after a diagnosis of isolated HG-PIN in a needle biopsy. This risk level is lower than the previously reported risk of 33% to 50%. HG-PIN is a risk factor for carcinoma detection only when found on consecutive sextant biopsies. The data presented here should prompt reconsideration of repeat biopsy strategies for HG-PIN, and re-evaluation of the absolute necessity of repeat biopsy for all patients with HG-PIN.

Section snippets

Material and methods

Between 1992 and 2001, all patients (24,893 men) in a prostate-specific antigen (PSA)-based screening program, aged 40 years or older (range 40 to 95), were screened. Unselected, consecutively recruited, men underwent PSA measurement at 6-month or 1-year intervals, depending on the findings of the screening tests. Men were recommended to return for screening 6 months later if they had an elevated PSA level or suspicious digital rectal examination (DRE) findings or to return 1 year later if

Results

The clinical findings for the HG-PIN study and benign prostatic tissue control groups are presented in Table I. Significant differences were present with respect to PSA level and presence of suspicious DRE findings, but not for the number of cores. Although the overall median number of cores obtained per biopsy session was 6, in 2000 (the last year for case identification), the median number was 7.5.

The proportion of patients diagnosed with carcinoma after an initial diagnosis of HG-PIN was

Comment

The data presented here indicated a cumulative risk of prostate cancer detection of 30.5% in serial repeat biopsies after a diagnosis of HG-PIN in an initial prostate needle biopsy. This level of risk is substantially lower than the 47% to 51% we previously reported in our screening population.3, 7 It is also lower than most published series, in which a detection rate of greater than 33% has been reported.24, 27

The incidence of carcinoma at follow-up repeat biopsy after an initial diagnosis of

Conclusions

A diagnosis of HG-PIN in needle biopsy tissue carries a 30.5% risk of carcinoma detection in follow-up biopsies in this series of a PSA-based screening population. This risk is lower than previously reported in many studies and not significantly different from that for a diagnosis of benign prostatic tissue, except when HG-PIN was diagnosed on consecutive repeat biopsies. Overall, the data suggest the need for a re-evaluation of the necessity for repeat biopsy in all patients with isolated

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CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia
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Citation Excerpt :
High-grade prostatic intraepithelial neoplasia (HGPIN) is frequently seen adjacent to acinar adenocarcinoma while isolated HGPIN is diagnosed in up to 16% of biopsies [3]. While low-grade PIN seems to lack prognostic and clinical implications, and therefore should not be mentioned in pathology reports, the clinical handling of focal HGPIN in biopsies in absence of adjacent adenocarcinoma remains controversial [4,5]. Of note, the risk for invasive carcinoma in follow-up biopsies subsequently acquired after diagnosis of isolated HGPIN or only benign lesions in initial needle biopsies lacks significant differences [6].
High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.
Multiparametric MR can identify high grade prostatic intraepithelial neoplasia (HGPIN) lesions and predict future detection of prostate cancer in men with a negative initial prostate biopsy
2016, Magnetic Resonance Imaging
This study aims to determine the pre-biopsy diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) characteristics of patients with high-grade prostatic intraepithelial neoplasia (HGPIN) and perform follow-up studies in these patients to assess the clinical implications.
One hundred sixteen men with prostate specific antigen between 4 and 10 ng/ml underwent pre-biopsy MR examinations. Nine of them had HGPIN lesions without concomitant prostate cancer (PCa) on biopsy. Apparent diffusion coefficient (ADC) and metabolite ratio [Citrate/(Choline + Creatine)] were calculated and these 9 patients were followed to determine the clinical outcomes.
Mean ADC for HGPIN foci was 1.01 ± 0.16 × 10^− 3 mm²/s while for the normal peripheral zone it was 1.69 ± 0.25 × 10^− 3 mm²/s (p < 0.005). Mean metabolite ratio for voxels in the HGPIN region of initial biopsy was 0.24 ± 0.16 while for the normal peripheral zone the value was 2.66 ± 1.57 (p < 0.005). Four of 5 patients who were available for follow-up were detected to have prostate cancer on repeat biopsy. No significant change in metabolite ratio and PSA was observed while ADC showed further reduction on follow-up.
HGPIN foci have ADC and metabolite ratio values similar to adenocarcinoma prostate, indicating that such patients have a high likelihood of developing cancer. DWI may help identify such men who may be candidates for close follow-up.
High Grade Prostatic Intraepithelial Neoplasia and Atypical Glands
2016, Prostate Cancer: Science and Clinical Practice: Second Edition
Historically, high-grade prostatic intraepithelial neoplasia (HGPIN) has been considered a premalignant lesion characterized by atypical proliferation and nuclear features in the setting of benign appearing acini and ducts. Rates of concurrent cancer after initial sextant biopsy diagnosis of HGPIN in the past were much higher due to undersampling, resulting in increased rates of cancer detection with immediate repeat biopsy. Currently, improved identification of smaller foci of cancer with initial extended core prostate biopsy has obviated the need for repeat biopsy in most patients diagnosed with HGPIN, given a similar cancer detection rate to those with a completely benign baseline biopsy. The exception is the subset of patients found to have multifocal HGPIN who continue to be at increased risk for subsequent cancer detection.
In contrast, atypical small acinar proliferation (ASAP) is a diagnostic category signaling the presence of pathologic features suspicious but not definitive for malignancy. The most common cause for this diagnostic ambiguity is small size of the foci of atypical glands. Frequently, this diagnosis represents undersampling of concurrent adenocarcinoma, thus the rate of subsequent cancer diagnosis is high, ranging from 27% to 71%. As a result, expert consensus suggests that patients with this finding on initial biopsy should be followed closely and undergo at least one short interval repeat biopsy for risk restratification.
Optimization of prostate biopsy: Review of technique and complications
2014, Urologic Clinics of North America
Citation Excerpt :
Epstein and Herawi50 have asserted that the risk of prostate cancer at repeat prostate biopsy after HGPIN diagnosis (22%) is similar to the risk of cancer detection after an initial benign biopsy. In addition, prospective trials have failed to demonstrate an association between the presence of HGPIN at initial prostate biopsy and subsequent prostate cancer at repeat prostate biopsy.51,52 However, studies by Benecchi and colleagues53 and Netto and Epstein54 have identified the presence of HGPIN as a risk factor in their analyses, and included HGPIN in their repeat prostate biopsy nomograms.
Preneoplasia in the prostate gland with emphasis on high grade prostatic intraepithelial neoplasia
2013, Pathology
There are a variety of morphological patterns and processes that have been implicated in the pathogenesis of prostate cancer. Prostatic intraepithelial neoplasia (PIN), inflammation with or without atrophy, and adenosis (atypical adenomatous hyperplasia) have all been given candidate status as precursor lesions of prostatic adenocarcinoma. Based on decades of research, high grade prostatic intraepithelial neoplasia (HPIN), a proliferative lesion of prostatic secretory cells, has emerged as the most likely morphological preinvasive lesion involved in the evolution of many but not all prostatic adenocarcinomas. In this manuscript, we briefly discuss other proposed precursors of prostatic adenocarcinoma and then focus on the history, diagnostic criteria and morphology of HPIN. The incidence of HPIN and its relationship to prostate cancer is reviewed. The differential diagnosis of large glandular patterns in the prostate is discussed in depth. Finally, we summarise the recent clinicopathological studies evaluating the clinical significance of HPIN and discuss follow-up strategies in men diagnosed with HPIN.
Optimizing performance and interpretation of prostate biopsy: A critical analysis of the literature
2010, European Urology
The number and location of biopsy cores and the interpretation of prostate biopsy in different clinical settings remain the subjects of continuing debate.
Our aim was to review the current evidence regarding the performance and interpretation of initial, repeat, and saturation prostatic biopsy.
A comprehensive Medline search was performed using the Medical Subject Heading search terms prostate biopsy, prostate cancer, detection, transrectal ultrasound (TRUS), nomogram, and diagnosis. Results were restricted to the English language, with preference given to those published within the last 3 yr.
At initial biopsy, a minimum of 10 but not >18 systematic cores are recommended, with 14–18 cores in glands ≥50 cm³. Biopsies should be directed laterally, and transition zone (TZ) cores are not recommended in the initial biopsy setting. Further biopsy sets, either as an extended repeat or as a saturation biopsy (≥20 cores) including the TZ, are warranted in young and fit men with a persistent suspicion of prostate cancer. An immediate repeat biopsy is not indicated for prior high-grade prostatic intraepithelial neoplasia diagnosis given an adequate extended initial biopsy. Conversely, biopsies with atypical glands that are suspicious but not diagnostic of cancer should be repeated within 3–6 mo. Overall recommendations for further biopsy sets (a third set or more) cannot be made. Transrectal ultrasound–guided systematic biopsies represent the standard-of-care method of prostate sampling. However, transperineal biopsies are an up-to-standard alternative.
The optimal prostatic biopsy regimen should be based on the individualized clinical setting of the patient and should follow the minimum standard requirements reported in this paper.

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Adult urologyHigh-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: Current level of risk in screening population

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Material and methods

Results

Comment

Conclusions

Urology

Hum Pathol

J Urol

J Urol

J Urol

J Urol

J Urol

J Urol

J Urol

Urology

J Urol

J Urol

Urology

J Urol

Adult urology
High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: Current level of risk in screening population