Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

High-Grade Prostatic Intraepithelial Neoplasia

  • Alessia Cimadamore
  • Maria Rosaria Raspollini
  • Rodolfo MontironiEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4915-1



High-grade prostatic intraepithelial neoplasia (HGPIN) is a neoplastic proliferation of secretory cells within preexisting ducts and acini, with cytological changes resembling those seen in cancer. HGPIN is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence.

Clinical Features

  • Incidence

    The mean incidence of HGPIN in prostatic needle biopsies is about 5%.

  • Age

    Patients aged 50–60 years.

  • Sex


  • Site

    The most commonly location is in the peripheral zone of the prostate.

  • Treatment

    Treatment is not indicated. Prophylactic RP or radiation is not an acceptable treatment. Patients with isolated HGPIN in needle biopsy may be considered for enrolment into clinical trials with chemoprevention agents. 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.

  • Outcome

    The risk of cancer detection following HGPIN on biopsy is 20–30%, not significantly higher than that following a benign biopsy (De Marzo et al. 2016; Epstein and Herawi 2006; Herawi et al. 2006).


HGPIN is not identified macroscopically.


Histological characteristics at low magnification:
  • The epithelial lining of the ducts and acini is darker than that of the surrounding normal ducts and acini.

  • It is thicker.

  • There may be a complex intraluminal pattern of growth.

Histological characteristics at high magnification:
  • Varying degrees of nuclear stratification and enlargement

  • Hyperchromasia

  • Nucleolar prominence

The morphologic spectrum of the cell changes can be subdivided into:
  • Low-grade PIN (PIN 1).

  • High-grade PIN (PIN 2 and 3): The cells resemble those of a microacinar adenocarcinoma with Gleason pattern 3.

There are four architectural patterns (flat, tufted, micropapillary, and cribriform). Unusual variants include HGPIN with signet ring-like features, with mucin cell metaplasia, with mucinous features, with foamy features, with inverted nuclei, with Paneth-like neuroendocrine differentiation, with squamous differentiation, and with small cells (not a neuroendocrine lesion) (Bostwick et al. 1993; Moch et al. 2016) (Fig. 1).
Fig. 1



The basal cell markers p63 and 34βE12 show a fragmented basal cell layer. Immunostaining for AMACR is positive as in adenocarcinoma.

Molecular Features

HGPIN shares similar genetic alterations with cancer including ERG protein expression and PTEN loss. PIN is epigenetically similar to cancer (Montironi et al. 2011; Zhou 2018).

Differential Diagnosis

The differential diagnosis is with:

Benign mimickers: Central zone histology, clear cell cribriform histology, and basal cell hyperplasia.

Malignant mimickers: Intraductal carcinoma, ductal adenocarcinoma, PIN-like ductal adenocarcinoma, and cribriform acinar adenocarcinoma (Moch et al. 2016; Zhou 2018).

References and Further Reading

  1. Bostwick, D. G., Amin, M. B., Dundore, P., et al. (1993). Architectural patterns of high-grade prostatic intraepithelial neoplasia. Human Pathology, 24, 298–310.CrossRefGoogle Scholar
  2. De Marzo, A. M., Haffner, M. C., Lotan, T. L., et al. (2016). Premalignancy in prostate cancer: Rethinking what we know. Cancer Prevention Research, 9, 648–656.CrossRefGoogle Scholar
  3. Epstein, J. I., & Herawi, M. (2006). Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: Implications for patient care. The Journal of Urology, 175 (Part 1), 820–834.CrossRefGoogle Scholar
  4. Herawi, M., Kahane, H., Cavallo, C., et al. (2006). 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. The Journal of Urology, 175, 121–124.CrossRefGoogle Scholar
  5. Moch, H., Humphrey, P. A., Ulbrigh, T. M., & Reutere, V. E. (Eds.). (2016). WHO classification of Tumours of the urinary system and male genital organs. Lyon: International Agency for Research on Cancer.Google Scholar
  6. Montironi, R., Mazzucchelli, R., Lopez-Beltran, A., et al. (2011). Prostatic intraepithelial neoplasia: Its morphological and molecular diagnosis and clinical significance. BJU International, 108, 1394–1401.CrossRefGoogle Scholar
  7. Zhou, M. (2018). High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate. Modern Pathology, 31(S1), S71–S79.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Alessia Cimadamore
    • 1
  • Maria Rosaria Raspollini
    • 2
  • Rodolfo Montironi
    • 1
    Email author
  1. 1.Institute of Pathological Anatomy and HistopathologyPolytechnic University of the Marche Region (Ancona)AnconaItaly
  2. 2.Histopathology and Molecular DiagnosticsUniversity Hospital CareggiFlorenceItaly