Prostate gland & seminal vesicles
Atypical / intraductal lesions
High grade prostatic intraepithelial neoplasia (HGPIN)


Minor changes: 15 January 2021

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PubMed Search: High grade prostatic intraepithelial neoplasia [title] free full text [SB]

Margaret Sanders, M.D.
Murali Varma, M.B.B.S.
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Cite this page: Sanders M, Varma M. High grade prostatic intraepithelial neoplasia (HGPIN). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/prostateHGPIN.html. Accessed January 22nd, 2021.
Definition / general
  • Putative precursor of prostatic adenocarcinoma
Essential features
  • Nucleoli visible at 200x magnification (Am J Surg Pathol 1995;19:873)
  • Surrogate marker for missed cancer in negative prostate biopsies; less useful in contemporary practice as lower incidence of unsampled prostate cancer with extended biopsy protocols
  • No clinical utility in radical prostatectomies and biopsies containing foci suspicious or diagnostic of prostate cancer
  • Would not account for raised serum PSA or radiological abnormality
Terminology
  • Formerly known as severe dysplasia, PIN 2 / PIN 3 and carcinoma in situ
  • PIN = high grade prostatic intraepithelial neoplasia (HGPIN); low grade PIN is not reported due to wide interobserver variability (Am J Surg Pathol 1995;19:873)
ICD coding
  • ICD-O: 8148/2 - glandular intraepithelial neoplasia, high grade
  • ICD-10: D07.5 - carcinoma in situ of prostate
  • ICD-11: 2E67.5 - carcinoma in situ of prostate
Epidemiology
Sites
  • Prostate gland
Clinical features
  • Would not account for elevated serum PSA or abnormal digital examination findings or radiological abnormality
Diagnosis
  • Diagnosis is made on histologic examination of biopsied prostate tissue, typically from a needle core biopsy
Radiology description
  • No radiological abnormality
Prognostic factors
  • Contemporary value of HGPIN as predictor of missed cancer is contentious
    • Risk of finding cancer on rebiopsy following unifocal HGPIN diagnosis is similar to benign diagnosis [ref already provided]
    • Risk of finding cancer on rebiopsy following multifocal HGPIN (2 or more cores) diagnosis is substantially higher at 30 - 40% (Pathology 2010;42:325, Can Urol Assoc J 2010;4:434, J Urol 2009;182:485, Urol Oncol 2020;S1078-1439:30488)
    • Cancers associated with HGPIN diagnosis on initial biopsy are more likely to be low grade and organ confined versus cancers diagnosed in the first biopsy without preexisting HGPIN [ref]
  • Prostate cancer detected at rebiopsy following diagnosis of HGPIN generally low grade and organ confined (Can J Urol 2015;22:8056, J Urol 2009;181:1069, Am J Surg Pathol 2011;35:1165)
    • Rebiopsy Gleason ≥ 7 rate following diagnosis of HGPIN in contemporary practice similar to that following an initial benign biopsy (17% versus 14%) (Hum Pathol 2018;79:116)
Case reports
Treatment
Microscopic (histologic) description
  • Diagnostic feature: prominent nucleoli visible at 200x or lower magnification
  • Medium to large ducts and acini with enlarged hyperchromatic nuclei and amphophilic cytoplasm
  • Common architectural patterns:
    • Flat: 1 - 2 layers of simple epithelium
    • Tufted: stratified epithelium with small luminal protrusions
    • Micropapillary: filliform structures lacking true fibrovascular core
    • Cribriform: epithelial proliferation with punched out spaces but lacks marked nucleomegaly indicative of intraductal carcinoma (Arch Pathol Lab Med 2020 Jun 26 [Epub ahead of print])
  • Less common patterns: signet ring cell, foamy gland, mucinous, inverted and small cell neuroendocrine (Am J Surg Pathol 1997;21:1215, Rev Urol 2004;6:171, Oncol Lett 2015;10:2395)
Microscopic (histologic) images

Contributed by Murali Varma, M.D.
Flat HGPIN

Flat HGPIN

Tufted HGPIN Tufted HGPIN Tufted HGPIN

Tufted HGPIN

Micropapillary and flat HGPIN

Micropapillary and flat HGPIN

Micropapillary HGPIN

Micropapillary HGPIN


Inverted HGPIN

Inverted HGPIN

p63

p63

CK5/6

CK5/6

AMACR

AMACR

Virtual slides

Images hosted on other servers:

Extensive HGPIN

Positive stains
Negative stains
Molecular / cytogenetics description
  • Deletions of 8p most common allelic loss; telomere shortening activity similar to prostatic adenocarcinoma
  • Other chromosomal abnormalities in both HGPIN and carcinoma include gains of chromosomes 7, 8, 10 and 12 (Am J Surg Pathol 1995;19:506, Rev Urol 2004;6:171)
  • TMPRSS - ERG fusion (Science 2005;310:644, Clin Cancer Res 2008;14:3380)
    • Found in approximately 50% of prostate carcinoma
    • Present in approximately 20% of HGPIN admixed with adenocarcinoma
    • Less common in HGPIN not associated with invasive adenocarcinoma
  • Hypermethylation GSPT1, the most common epigenetic change in prostate carcinoma, is also seen in HGPIN
  • Other genetic features of HGPIN
Sample pathology report
  • Prostate, left lateral mid, needle core biopsy:
    • High grade prostatic intraepithelial neoplasia
Differential diagnosis
Board review style question #1

Which of the following is true about this prostatic lesion?

  1. Clinically identifiable as a palpable mass lesion on digital rectal examination
  2. More common in Asians
  3. Not associated with raised serum PSA
  4. Nucleolar prominence at magnification 400x is a diagnostic feature of this lesion
  5. PIRADS 5 on MRI
Board review style answer #1
C. It is not associated with raised serum PSA. This is high grade prostatic intraepithelial neoplasia.

Comment Here

Reference: High grade prostatic intraepithelial neoplasia (HGPIN)
Board review style question #2
Which of the following is the common immunoprofile of high grade PIN?

  1. HMWCK-, p63-, AMACR-
  2. HMWCK-, p63-, AMACR+
  3. HMWCK-, p63+, AMACR-
  4. HMWCK+, p63+, AMACR-
  5. HMWCK+, p63+, AMACR+
Board review style answer #2
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