Prostatic intraepithelial neoplasia (PIN)
High grade PIN - general

Author: Monika Roychowdhury, M.D. (see Authors page)

Revised: 26 October 2015, last major update June 2012

Copyright: (c) 2003-2015,, Inc.

PubMed Search: High grade PIN [title]
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Cite this page: High grade PIN. website. Accessed January 21st, 2019.
Definition / general
  • Incidence on needle biopsy is reported as 5% to 8% (71% to 83% in prostatectomy specimens)
  • Present in 14% of patients in a community hospital study
  • Indicates 21% risk of carcinoma in subsequent biopsies
  • Low risk for cancer (13%) if two subsequent biopsies are negative
  • Number of cores with high grade PIN predicts risk of subsequent cancer (1 core, 30%; 3 cores, 40%; 4+ cores, 75%), predominantly cribriform/micropapillary patterns also predict higher risk (Am J Surg Pathol 2001;25:1079)
  • In Americans less than 60 years old, more common in blacks vs. whites
  • Does not cause elevated PSA
  • If found on TURP specimen, should examine all submitted tissue for invasive adenocarcinoma
  • 50% are aneuploid
  • Patterns include apocrine, cribriform, flat, foamy gland, inverted (hobnail), micropapillary, mucinous, Paneth cell-like, pleomorphic, signet-ring cell, small cell neuroendocrine, tufting
Microscopic (histologic) description
  • The hallmark distinguishing low-grade and high-grade PIN is the presence of prominent nucleoli
  • Histologically characterised by prostate glands retaining a complete or partial basal cell layer lined by atypical cells with prominent nucleoli
  • Low power diagnosis
  • Usual patterns are micropapillary / cribriform (70%), flat / tufted (20%)
  • Basophilic appearance at low power due to enlarged hyperchromatic nuclei and amphophilic cytoplasm
  • May develop tall papillary tufts
  • Frequently multicentric in prostatectomy specimens
  • Identifiable on low power as glands with:
    • Papillary projections into lumina
    • Hyperchromasia
    • Enlarged nuclei
    • Pleomorphism
    • Stratification/crowding
    • Prominent nucleoli
  • Cells may contain pigment, may have intraluminal mucin staining similar to invasive carcinoma
  • May also show apocrine, foamy gland, mucinous, paneth, signet ring, small cell neuroendocrine, squamous cells, making its distinction from carcinoma challenging
  • Microscopic (histologic) images

    Various images

    Positive stains
  • Basal cells: CK903, p63, CD10 (Hum Pathol 2003;34:450)
  • Secretory cells: P504S/AMACR (Am J Surg Pathol 2003;27:772)
  • Current investigations: HGPIN adjacent to carcinoma is more likely to show AMACR expression (56%) than HGPIN distant from carcinoma (14%); those with any HGPIN gland that is AMACR+ are 5.2x more likely to show carcinoma on repeat biopsy than completely AMACR-negative HGPIN
  • Molecular / cytogenetics description
  • Frequent loss of 8p and gain of 8q, telomere shortening and increased telomere activity similar to prostatic adenocarcinoma
  • Other chromosomal abnormalities in both HGPIN and carcinoma include losses of 10q, 16q and 18q and gains of chromosomes 7, 10, 12 and Y
  • Differential diagnosis
  • Central zone glands: at base of prostate adjacent to seminal vesicles; usually cribriform or Roman arch formation at end of core biopsy; tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer; associated thick muscle bundles of bladder neck, no cytologic atypia (Hum Pathol 2002;33:518)
  • Clear cell cribriform hyperplasia: clear cytoplasm, benign nuclei, no/small nucleoli, prominent basal cell layer
  • Seminal vesicle glands with cribriform epithelium and no atypia: normal finding
  • Additional references