Prostate gland & seminal vesicles
Atypical / intraductal lesions

Topic Completed: 1 June 2012

Minor changes: 5 October 2020

Copyright: 2003-2020,, Inc.

PubMed Search: High grade PIN [title]

Monika Roychowdhury, M.D.
Maria Tretiakova, M.D., Ph.D.
Page views in 2019: 11,008
Page views in 2020 to date: 9,370
Cite this page: Reder NP, Roychowdhury M, Tretiakova M. HGPIN. website. Accessed October 29th, 2020.
Definition / general
  • Glands that have acinar cells with prominent nucleoli at 20x or lower magnification with retained basal cells
  • Four dominant patterns: cribriform, tufting, micropapillary and flat (Hum Pathol 1993;24:298)
  • Often have AMACR increased expression
  • Does not cause elevated PSA
Prognostic factors
  • 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, J Urol 2006;175:820)
  • If found on TURP specimen, should examine all submitted tissue for invasive adenocarcinoma
  • No known clinical difference between the morphologic variants of HGPIN; primary utility is for diagnostic and prognostic purposes (BJU Int 2011;108:1394)
  • Repeat biopsy is recommended for multifocal HGPIN within 1 year with possible increased sampling of the initial site
Case reports
Microscopic (histologic) description
  • Hallmark feature is acinar cells with presence of prominent nucleoli visible at a 20x magnification or lower
  • Retained complete or partial basal cell layer
  • Usual patterns are micropapillary / cribriform (70%), flat / tufted (20%)
  • May develop tall papillary tufts
  • Frequently multicentric in prostatectomy specimens
  • Identifiable on low power as glands with:
    • Basophilic appearance due to enlarged hyperchromatic nuclei and amphophilic cytoplasm
    • Papillary projections into lumina
    • Pleomorphism
    • Stratification / crowding
    • Prominent nucleoli
  • Cribriform pattern is characterized by simple architecture, round contours and irregular slit-like spaces
  • 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

Contributed by Nicholas P. Reder, M.D., M.P.H.

HGPIN cribriform pattern

HGPIN foamy pattern

Positive stains
  • Basal cells: high molecular weight cytokeratin (34betaE12 / CK903), p63, CD10 (Hum Pathol 2003;34:450)
  • Acinar 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- HGPIN
Negative stains
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
  • 50% are aneuploid
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)
    • Roman bridge formation can be present but the nuclei often stream parallel; no nuclear atypia
  • Intraductal carcinoma:
    • Nucleomegaly (6x of the adjacent normal nuclei)
    • Larger (> 1 mm, > 6 glands)
    • Often has central necrosis
    • Marked nuclear pleomorphism
    • Higher mitotic rate
    • Usually associated with infiltrative high grade carcinoma
  • Clear cell cribriform hyperplasia:
    • Clear cytoplasm, bland nuclei
    • No / small nucleoli
    • Prominent basal cell layer
  • Seminal vesicle glands:
    • Can have cribriform epithelium and prominent nucleoli
    • Characteristic pigment can be seen
  • Basal cell hyperplasia:
    • Glands are small, crowded in back to back arrangement and with round to elongated palisading nuclei
    • A high molecular weight cytokeratin stain can be useful in difficult cases
  • Carcinoma, cribriform Gleason pattern 4:
    • Lack basal cells
    • Infiltrative
    • Has greater nuclear atypia
    • More round punched out spaces rather than irregular slit-like spaces
  • Atrophy and postatrophic hyperplasia:
    • Smaller nuclei, less cytoplasm; nuclei touch cell membrane
    • Abundant stromal sclerosis
  • Urothelial metaplasia:
    • Lacks nucleomegaly and prominent nucleoli
  • Foamy gland carcinoma:
    • Similar cytology to foamy HGPIN but absent basal cell layer, smaller glands and infiltrative pattern
  • Low grade urothelial carcinoma:
    • Uniform tall columnar cells with a modest amount of pale to clear cytoplasm
    • Nuclei are hyperchromatic, basally located and have prominent nucleoli
    • Grows in expansile nodules in the transition zone
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