The risk of cancer detection following high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy is ∼20–30%, which is not significantly higher than that following a benign biopsy
The majority of cancers detected following a diagnosis of HGPIN are Gleason score 6 (grade group 1)
Men with a single core positive for HGPIN do not require routine repeat biopsy; in multifocal HGPIN, follow-up monitoring could include serum and urine tests or imaging
The risk of cancer following atypical glands suspicious for carcinoma on needle biopsy is ∼40% — twofold higher than that following a benign biopsy
∼20% of cancers detected after atypical glands suspicious for carcinoma are Gleason score 3 + 4 = 7 (grade group 2) or higher, including 5% with Gleason scores 8–10 (grade group 4–5)
Follow-up monitoring is warranted following atypical glands suspicious for carcinoma; in select patients, subsequent biopsies should be considered, with increased sampling of atypical regions
Prostate biopsy is the gold standard for diagnosing prostate cancer and reliable pathological assessment is essential for guiding management. Research efforts over the past few years have aimed to establish a more universal approach to management according to pathological grading; however, high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands suspicious for carcinoma are two diagnoses without standardized follow-up and treatment pathways. Much of this uncertainty is due to limited evidence describing the subsequent rates of cancer and high-grade cancer when HGPIN or atypical glands are detected on initial biopsy. Fortunately, data from the past decade have shed light on these phenomena, and an improved understanding of the implications of the presence of HGPIN and atypical glands on prostate biopsy means that clinical recommendations can be made for the management of patients with these diagnoses.
Subscribe to Journal
Get full journal access for 1 year
only $17.42 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Epstein, J. I. et al. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am. J. Surg. Pathol. 29, 1228–1242 (2005).
Epstein, J. I. et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am. J. Surg. Pathol. 40, 244–252 (2016).
Epstein, J. I. & Herawi, M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. J. Urol. 175, 820–834 (2006).
Tosoian, J. J., Carter, H. B., Lepor, A. & Loeb, S. Active surveillance for prostate cancer: current evidence and contemporary state of practice. Nat. Rev. Urol. 13, 205–215 (2016).
Herawi, M., Kahane, H., Cavallo, C. & Epstein, J. I. Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled. J. Urol. 175, 121–124 (2006).
Bostwick, D. G. & Qian, J. High-grade prostatic intraepithelial neoplasia. Mod. Pathol. 17, 360–379 (2004).
Haggman, M. J., Macoska, J. A., Wojno, K. J. & Oesterling, J. E. The relationship between prostatic intraepithelial neoplasia and prostate cancer: critical issues. J. Urol. 158, 12–22 (1997).
Chan, T. Y. & Epstein, J. I. Patient and urologist driven second opinion of prostate needle biopsies. J. Urol. 174, 1390–1394 (2005).
Goeman, L. et al. Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer? Prostate Cancer Prostatic Dis. 6, 305–310 (2003).
Abdel-Khalek, M., El-Baz, M. & Ibrahiem, E. Predictors of prostate cancer on extended biopsy in patients with high-grade prostatic intraepithelial neoplasia: a multivariate analysis model. BJU Int. 94, 528–533 (2004).
Algaba, F. Evolution of isolated high-grade prostate intraepithelial neoplasia in a Mediterranean patient population. Eur. Urol. 35, 496–497 (1999).
Moore, C. K. et al. Prognostic significance of high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation in the contemporary era. J. Urol. 173, 70–72 (2005).
Bishara, T., Ramnani, D. M. & Epstein, J. I. 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. 28, 629–633 (2004).
Gokden, N., Roehl, K. A., Catalona, W. J. & Humphrey, P. A. High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: current level of risk in screening population. Urology 65, 538–542 (2005).
Park, S., Shinohara, K., Grossfeld, G. D. & Carroll, P. R. Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy. J. Urol. 165, 1409–1414 (2001).
Girasole, C. R. et al. Significance of atypical and suspicious small acinar proliferations, and high grade prostatic intraepithelial neoplasia on prostate biopsy: implications for cancer detection and biopsy strategy. J. Urol. 175, 929–933 (2006).
Tan, P. H. et al. Is high-grade prostatic intraepithelial neoplasia on needle biopsy different in an Asian population: a clinicopathologic study performed in Singapore. Urology 68, 800–803 (2006).
Lopez, J. I. Prostate adenocarcinoma detected after high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. BJU Int. 100, 1272–1276 (2007).
Akhavan, A. et al. The proportion of cores with high-grade prostatic intraepithelial neoplasia on extended-pattern needle biopsy is significantly associated with prostate cancer on site-directed repeat biopsy. BJU Int. 99, 765–769 (2007).
Schoenfield, L. et al. The incidence of high-grade prostatic intraepithelial neoplasia and atypical glands suspicious for carcinoma on first-time saturation needle biopsy, and the subsequent risk of cancer. BJU Int. 99, 770–774 (2007).
Singh, P. B. et al. Risk of prostate cancer after detection of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on extended core needle biopsy: a UK hospital experience. BMC Urol. 9, 3 (2009).
He, H. et al. Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): lack of utility to stratify cancer risks associated with HGPIN. BJU Int. 110, E751–E755 (2012).
Netto, G. J. & Epstein, J. I. Widespread high-grade prostatic intraepithelial neoplasia on prostatic needle biopsy: a significant likelihood of subsequently diagnosed adenocarcinoma. Am. J. Surg. Pathol. 30, 1184–1188 (2006).
Rapp, D. E. et al. Recutting prostate needle core biopsies with high grade prostatic intraepithelial neoplasia increases detection of adenocarcinoma. Can. J. Urol. 16, 4484–4489 (2009).
Pettersson, A. et al. The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 21, 1497–1509 (2012).
Al-Hussain, T. O. & Epstein, J. I. Initial high-grade prostatic intraepithelial neoplasia with carcinoma on subsequent prostate needle biopsy: findings at radical prostatectomy. Am. J. Surg. Pathol. 35, 1165–1167 (2011).
Rosenkrantz, A. B. et al. Prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a prior negative biopsy: a consensus statement by AUA and SAR. J. Urol. 196, 1613–1618 (2016).
Heidenreich, A. et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur. Urol. 65, 124–137 (2014).
Carroll, P. R. et al. NCCN guidelines insights: prostate cancer early detection, version 2.2016. J. Natl Compr. Canc. Netw. 14, 509–519 (2016).
Russo, G. I. et al. A systematic review and meta-analysis of the diagnostic accuracy of prostate health index and 4-Kallikrein panel score in predicting overall and high-grade prostate cancer. Clin. Genitourin. Cancer 15, 429–439.e1 (2016).
Ma, T. M. et al. The role of multiparametric magnetic resonance imaging/ultrasound fusion biopsy in active surveillance. Eur. Urol. 71, 174–180 (2017).
Tosoian, J. J. et al. Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice. Prostate Cancer Prostatic Dis. 20, 228–233 (2017).
Tosoian, J. J. et al. Prostate Health Index density improves detection of clinically significant prostate cancer. BJU Int. http://dx.doi.org/10.1111/bju.13762 (2017).
Iczkowski, K. A. & Bostwick, D. G. Atypical small acinar proliferation of the prostate: 16 years' experience. Pathol. Case Rev. 19, 147–153 (2014).
Jiang, Z., Woda, B. A., Wu, C. L. & Yang, X. J. Discovery and clinical application of a novel prostate cancer marker: alpha-methylacyl CoA racemase (P504S). Am. J. Clin. Pathol. 122, 275–289 (2004).
Halushka, M. K., Kahane, H. & Epstein, J. I. Negative 34betaE12 staining in a small focus of atypical glands on prostate needle biopsy: a follow-up study of 332 cases. Hum. Pathol. 35, 43–46 (2004).
Borboroglu, P. G., Sur, R. L., Roberts, J. L. & Amling, C. L. Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy. J. Urol. 166, 866–870 (2001).
Postma, R., Roobol, M., Schroder, F. H. & van der Kwast, T. H. Lesions predictive for prostate cancer in a screened population: first and second screening round findings. Prostate 61, 260–266 (2004).
Fadare, O., Wang, S. & Mariappan, M. R. Practice patterns of clinicians following isolated diagnoses of atypical small acinar proliferation on prostate biopsy specimens. Arch. Pathol. Lab. Med. 128, 557–560 (2004).
Iczkowski, K. A., MacLennan, G. T. & Bostwick, D. G. Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases. Am. J. Surg. Pathol. 21, 1489–1495 (1997).
Iczkowski, K. A. et al. Diagnosis of “suspicious for malignancy” in prostate biopsies: predictive value for cancer. Urology 51, 749–758 (1998).
Chan, T. Y. & Epstein, J. I. Follow-up of atypical prostate needle biopsies suspicious for cancer. Urology 53, 351–355 (1999).
Zhang, M., Amberson, J. B. & Epstein, J. I. Two sequential diagnoses of atypical foci suspicious for carcinoma on prostate biopsy: a follow-up study of 179 cases. Urology 82, 861–864 (2013).
Leone, A. et al. Atypical small acinar proliferation: repeat biopsy and detection of high grade prostate cancer. Prostate Cancer 2015, 810159 (2015).
Warlick, C. et al. Rate of Gleason 7 or higher prostate cancer on repeat biopsy after a diagnosis of atypical small acinar proliferation. Prostate Cancer Prostatic Dis. 18, 255–259 (2015).
Dorin, R. P., Wiener, S., Harris, C. D. & Wagner, J. R. Prostate atypia: does repeat biopsy detect clinically significant prostate cancer? Prostate 75, 673–678 (2015).
Leone, A. et al. Atypical small acinar proliferation (ASAP): is a repeat biopsy necessary ASAP? A multi-institutional review. Prostate Cancer Prostatic Dis. 19, 68–71 (2016).
Chen, Y. B., Pierorazio, P. M. & Epstein, J. I. Initial atypical diagnosis with carcinoma on subsequent prostate needle biopsy: findings at radical prostatectomy. J. Urol. 184, 1953–1957 (2010).
Raskolnikov, D. et al. The role of image guided biopsy targeting in patients with atypical small acinar proliferation. J. Urol. 193, 473–478 (2015).
Iczkowski, K. A., Chen, H. M., Yang, X. J. & Beach, R. A. Prostate cancer diagnosed after initial biopsy with atypical small acinar proliferation suspicious for malignancy is similar to cancer found on initial biopsy. Urology 60, 851–854 (2002).
Pietzak, E. J. et al. The presence of high-grade prostatic intraepithelial neoplasia or atypia on prostate biopsy does not adversely affect prostatectomy outcomes for patients otherwise eligible for active surveillance. Urology 84, 1442–1447 (2014).
The authors declare no competing financial interests.
About this article
Cite this article
Tosoian, J., Alam, R., Ball, M. et al. Managing high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands on prostate biopsy. Nat Rev Urol 15, 55–66 (2018). https://doi.org/10.1038/nrurol.2017.134
Validating fPSA Glycoprofile as a Prostate Cancer Biomarker to Avoid Unnecessary Biopsies and Re-Biopsies
Biomarkers in Medicine (2018)
Nature Reviews Urology (2018)
Surgical Pathology Clinics (2018)