Prostate gland & seminal vesicles
Atypical / intraductal lesions
High grade prostatic intraepithelial neoplasia (HGPIN)
Authors: Margaret Sanders, M.D., Murali Varma, M.B.B.S.
Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Minor changes: 15 January 2021
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: High grade prostatic intraepithelial neoplasia [title] free full text [SB]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite 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
Epidemiology
- Needle biopsy prevalence: 0 - 25%, mean 7.7% (Korean J Urol 2012;53:297)
- Cystoprostatectomy prevalence: 11 - 34% (BJU Int 2007;99:780, Urology 2007;70:1100, Hum Pathol 2016;55:117)
- Earlier age and more diffuse in African Americans, lower incidence in Asians (Pathol Res Pract 1995;191:838)
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
- 60 year old man with foamy gland HGPIN (Am J Surg Pathol 2000;24:140)
- 69 year old man with foamy gland HGPIN (Human pathology case reports 2017;10:32)
Treatment
- Follow up PSA
- Repeat biopsy if PSA remains elevated
- No role for definitive treatment such as prostatectomy, radiotherapy or hormone ablation
- When HGPIN involves > 1 biopsy cores or sites, National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer Early Detection recommends extended pattern rebiopsy within 6 months with increased sampling of the affected site and adjacent areas
- If HGPIN involves only one core, the decision for rebiopsy is based on risk assessment using clinical, radiological, and laboratory findings
- No therapy is needed for HGPIN as an isolated finding in needle biopsy (Mod Pathol 2018;31:S71, NCCN.org: National Comprehensive Cancer Network Clinical Guidelines in Oncology: Prostate Cancer Early Detection, 2017 [Accessed 15 January 2021])
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
Tufted HGPIN
Micropapillary and flat HGPIN
Micropapillary HGPIN
Inverted HGPIN
p63
CK5/6
AMACR
Virtual slides
Images hosted on other servers:
Extensive HGPIN
Positive stains
- Basal cells: high molecular weight cytokeratin (34 beta E12 / CK903), p63; may be discontinuous
- Acinar cells: P504S / AMACR
- PTEN: normal retained pattern (Am J Surg Pathol 2015;39:169)
Negative stains
- ERG could be positive rare cases of HGPIN (see ERG, Am J Surg Pathol 2011;35:608)
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
- Aneuploidy (present in approximately 50%)
- Increased expression of CDKN2A, TP53, tumor suppressor genes involved in cell cycle regulation and MYC oncogene amplification (Clin Cancer Res 2001;7:544, Mod Pathol 1997;10:1113)
Sample pathology report
- Prostate, left lateral mid, needle core biopsy:
- High grade prostatic intraepithelial neoplasia
Differential diagnosis
- Prostatic central zone glands:
- Increased architectural complexity (cribriform / micropapillary)
- Cytologically bland with inconspicuous nucleoli
- Central / basal location
- Ejaculatory duct epithelium / seminal vesicle epithelium:
- May show cribriform architecture
- Increased nuclear pleomorphism and cytoplasmic golden lipofuscin pigment (degenerative phenomena)
- Usually immunonegative for prostatic markers
- Urothelial metaplasia:
- No architectural complexity
- No prominent nucleoli
- Inflammatory reactive atypia:
- No architectural complexity
- Inflammatory cells including polymorphs
- Reactive nuclear features
- Radiation atypia:
- No architectural complexity
- Nuclear pleomorphism but no macronucleoli
- Basal cells prominent
- Clear cell cribriform hyperplasia:
- Clear cytoplasm
- Inconspicuous nucleoli and lacks nucleomegaly
- Basal cell hyperplasia:
- Proliferation of peripheral basal cells showing prominent nucleoli
- Central secretory cells lack nucleoli
- Basal cell markers demonstrate basal cell predominance
- PIN-like carcinoma:
- Architecture resembling HGPIN
- Greater crowding / dilated glands lined by columnar pseudostratified cells
- May show cystically dilated glands lined by ductal type epithelium
- Immunonegative for basal cell markers (Am J Surg Pathol 2018;42:1693)
- Pattern 4 cribriform acinar adenocarcinoma:
- Confluent, increased architectural complexity
- Immunonegative for basal cell markers
- Ductal carcinoma:
- Peri-urethral or peripheral prostatic ductal location
- Expansive, complex cribriform / papillary / solid architecture
- Tall columnar cells, oval pleomorphic nuclei
- Immunonegative for basal cell markers (Med Princ Pract 2010;19:82)
- Intraductal carcinoma:
- Solid or dense cribriform architecture or loose cribriform or micropapillary with marked nuclear atypia or comedo necrosis (Virchows Arch 2019;474:525, Am J Surg Pathol 2016;40:e67)
- Markedly distended glands (Mod Pathol 2018;31:S71, Mod Pathol 2006;19:1528)
- HGPIN with adjacent atypical small glands (PINATYP):
- Unresolved differential of tangential sectioning / budding of HGPIN and invasive adenocarcinoma (Hum Pathol 2001;32:389)
- AMACR immunohistochemistry unhelpful: generally positive in both scenarios (Histopathology 2005;47:1)
Board review style question #1
Which of the following is true about this prostatic lesion?
- Clinically identifiable as a palpable mass lesion on digital rectal examination
- More common in Asians
- Not associated with raised serum PSA
- Nucleolar prominence at magnification 400x is a diagnostic feature of this lesion
- 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)
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?
- HMWCK-, p63-, AMACR-
- HMWCK-, p63-, AMACR+
- HMWCK-, p63+, AMACR-
- HMWCK+, p63+, AMACR-
- HMWCK+, p63+, AMACR+
Board review style answer #2
E. HMWCK+, p63+, AMACR+
Comment Here
Reference: High grade prostatic intraepithelial neoplasia (HGPIN)
Comment Here
Reference: High grade prostatic intraepithelial neoplasia (HGPIN)
