Managing high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands on prostate biopsy

Key Points

  • 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

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Multiple glands with high-grade prostatic intraepithelial neoplasia (HGPIN) on needle biopsy.
Figure 2: Several small atypical glands suspicious for carcinoma on the edge of a needle biopsy core.

References

  1. 1

    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).

    Article  Google Scholar 

  2. 2

    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).

    PubMed  Google Scholar 

  3. 3

    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).

    Article  Google Scholar 

  4. 4

    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).

    Article  Google Scholar 

  5. 5

    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).

    Article  Google Scholar 

  6. 6

    Bostwick, D. G. & Qian, J. High-grade prostatic intraepithelial neoplasia. Mod. Pathol. 17, 360–379 (2004).

    Article  Google Scholar 

  7. 7

    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).

    CAS  Article  Google Scholar 

  8. 8

    Chan, T. Y. & Epstein, J. I. Patient and urologist driven second opinion of prostate needle biopsies. J. Urol. 174, 1390–1394 (2005).

    Article  Google Scholar 

  9. 9

    Goeman, L. et al. Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer? Prostate Cancer Prostatic Dis. 6, 305–310 (2003).

    CAS  Article  Google Scholar 

  10. 10

    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).

    Article  Google Scholar 

  11. 11

    Algaba, F. Evolution of isolated high-grade prostate intraepithelial neoplasia in a Mediterranean patient population. Eur. Urol. 35, 496–497 (1999).

    CAS  Article  Google Scholar 

  12. 12

    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).

    Article  Google Scholar 

  13. 13

    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).

    Article  Google Scholar 

  14. 14

    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).

    Article  Google Scholar 

  15. 15

    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).

    CAS  Article  Google Scholar 

  16. 16

    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).

    Article  Google Scholar 

  17. 17

    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).

    Article  Google Scholar 

  18. 18

    Lopez, J. I. Prostate adenocarcinoma detected after high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. BJU Int. 100, 1272–1276 (2007).

    Article  Google Scholar 

  19. 19

    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).

    Article  Google Scholar 

  20. 20

    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).

    CAS  Article  Google Scholar 

  21. 21

    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).

    Article  Google Scholar 

  22. 22

    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).

    CAS  Article  Google Scholar 

  23. 23

    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).

    Article  Google Scholar 

  24. 24

    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).

    PubMed  Google Scholar 

  25. 25

    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).

    Article  Google Scholar 

  26. 26

    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).

    Article  Google Scholar 

  27. 27

    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).

    Article  Google Scholar 

  28. 28

    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).

    Article  Google Scholar 

  29. 29

    Carroll, P. R. et al. NCCN guidelines insights: prostate cancer early detection, version 2.2016. J. Natl Compr. Canc. Netw. 14, 509–519 (2016).

    Article  Google Scholar 

  30. 30

    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).

    Article  Google Scholar 

  31. 31

    Ma, T. M. et al. The role of multiparametric magnetic resonance imaging/ultrasound fusion biopsy in active surveillance. Eur. Urol. 71, 174–180 (2017).

    Article  Google Scholar 

  32. 32

    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).

    CAS  Article  Google Scholar 

  33. 33

    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).

  34. 34

    Iczkowski, K. A. & Bostwick, D. G. Atypical small acinar proliferation of the prostate: 16 years' experience. Pathol. Case Rev. 19, 147–153 (2014).

    Article  Google Scholar 

  35. 35

    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).

    CAS  Article  Google Scholar 

  36. 36

    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).

    CAS  Article  Google Scholar 

  37. 37

    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).

    CAS  Article  Google Scholar 

  38. 38

    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).

    Article  Google Scholar 

  39. 39

    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).

    PubMed  Google Scholar 

  40. 40

    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).

    CAS  Article  Google Scholar 

  41. 41

    Iczkowski, K. A. et al. Diagnosis of “suspicious for malignancy” in prostate biopsies: predictive value for cancer. Urology 51, 749–758 (1998).

    CAS  Article  Google Scholar 

  42. 42

    Chan, T. Y. & Epstein, J. I. Follow-up of atypical prostate needle biopsies suspicious for cancer. Urology 53, 351–355 (1999).

    CAS  Article  Google Scholar 

  43. 43

    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).

    Article  Google Scholar 

  44. 44

    Leone, A. et al. Atypical small acinar proliferation: repeat biopsy and detection of high grade prostate cancer. Prostate Cancer 2015, 810159 (2015).

    Article  Google Scholar 

  45. 45

    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).

    CAS  Article  Google Scholar 

  46. 46

    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).

    Article  Google Scholar 

  47. 47

    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).

    CAS  Article  Google Scholar 

  48. 48

    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).

    Article  Google Scholar 

  49. 49

    Raskolnikov, D. et al. The role of image guided biopsy targeting in patients with atypical small acinar proliferation. J. Urol. 193, 473–478 (2015).

    Article  Google Scholar 

  50. 50

    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).

    Article  Google Scholar 

  51. 51

    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).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

J.J.T., R.A. and M.W.B. researched data for article. J.J.T. and R.A. wrote the manuscript. All authors made a substantial contribution to discussion of content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Jeffrey J. Tosoian.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing