Definition/General
Introduction:
PIN is dysplastic changes in prostatic epithelium
Considered precursor to adenocarcinoma
High-grade PIN (HGPIN) clinically significant
Shows preserved basal cell layer
Architectural changes with cellular atypia.
Origin:
Arises from prostatic ductal epithelium
Shows dysplastic transformation
Preserved glandular architecture
Intact basal cell layer
Precursor lesion to cancer.
Classification:
Current: High-grade PIN (HGPIN) only
Historical: Low-grade PIN (no longer reported)
Architectural patterns: Tufting, micropapillary, cribriform, flat
Multifocal disease common.
Epidemiology:
Incidence increases with age
Peak 6th-7th decades
Precedes cancer by 5-10 years
Found in 9% of biopsies
Associated with cancer (35% risk).
Clinical Features
Presentation:
Asymptomatic
Elevated PSA
Abnormal DRE
Incidental finding
No specific symptoms
Concurrent with BPH.
Symptoms:
No specific symptoms
Lower urinary tract symptoms (from BPH)
Urinary frequency
Weak stream
Nocturia.
Risk Factors:
Advancing age
Family history
African ancestry
Hormonal factors
Diet (high fat)
Genetic predisposition.
Screening:
PSA testing
Digital rectal examination
Transrectal biopsy
MRI-guided biopsy
Repeat biopsy recommended.
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Gross Description
Appearance:
No gross abnormalities
Similar to normal prostate
May have nodular appearance
No specific features
Microscopic diagnosis.
Characteristics:
Normal gross appearance
Tan-gray color
Firm consistency
No mass lesion
Requires microscopic examination.
Size Location:
Peripheral zone predominantly
Transition zone involvement
Multifocal distribution
No specific size
Scattered throughout.
Multifocality:
Multifocal disease common
Bilateral involvement
Variable extent
Associated with cancer foci
Field effect changes.
Microscopic Description
Histological Features:
Cellular stratification
Nuclear enlargement
Prominent nucleoli
Preserved basal cell layer
Intact basement membrane
Architectural distortion.
Cellular Characteristics:
Enlarged nuclei (3x normal)
Prominent nucleoli
Increased nuclear-cytoplasmic ratio
Nuclear hyperchromasia
Mitotic figures increased.
Architectural Patterns:
Tufting pattern
Micropapillary
Cribriform
Flat pattern
Preserved gland outline
Luminal proliferation.
Grading Criteria:
Only HGPIN reported
Criteria: Nuclear enlargement
Nucleolar prominence
Architectural complexity
Preserved basal cells.
Immunohistochemistry
Positive Markers:
34βE12 - positive (basal cells)
p63 - positive (basal cells)
PSA - positive (luminal cells)
PSAP - positive
Cytokeratin 8/18 - positive.
Negative Markers:
AMACR - negative to focally positive
Chromogranin A - negative
Synaptophysin - negative.
Diagnostic Utility:
Basal cell markers confirm benign nature
34βE12/p63 highlight intact basal layer
AMACR may be focally positive
PSA confirms prostatic origin.
Molecular Subtypes:
All PIN: Intact basal cell layer
HGPIN: Nuclear atypia with preserved architecture
Reactive changes: Less atypia, inflammation.
Molecular/Genetic
Genetic Mutations:
Chromosomal instability
8q gain (MYC amplification)
Loss of 8p
NKX3.1 loss
GSTP1 hypermethylation
Telomerase activation.
Molecular Markers:
p53 alterations
MYC overexpression
NKX3.1 loss
Rb pathway alterations
DNA hypermethylation.
Prognostic Significance:
Cancer risk: 35% at repeat biopsy
Multifocal HGPIN: Higher risk
Extensive HGPIN: Increased cancer risk
Follow-up required.
Therapeutic Targets:
Active surveillance
Repeat biopsy (6-12 months)
Chemoprevention trials
MRI monitoring
No specific treatment.
Differential Diagnosis
Similar Entities:
Prostatic adenocarcinoma
Atypical adenomatous hyperplasia
Reactive epithelial changes
Cribriform hyperplasia
Basal cell hyperplasia.
Distinguishing Features:
PIN: Basal cells present, preserved glands
Adenocarcinoma: Basal cells absent, AMACR+
AAH: Crowded glands, minimal atypia
Reactive: Less atypia, inflammation
BCP: Basal cell proliferation.
Diagnostic Challenges:
Tangential sectioning
Crush artifact
Atrophy with atypia
Limited tissue
Reactive changes.
Rare Variants:
PIN with neuroendocrine differentiation
PIN in atrophic glands
PIN with squamous metaplasia.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Number] core prostate biopsies
PIN Identification
High-grade prostatic intraepithelial neoplasia (HGPIN) identified in [X] of [Y] cores
Architectural Patterns
Pattern: [Tufting/Micropapillary/Cribriform/Flat/Mixed]
Extent
Extent: [Focal/Multifocal/Extensive]
Basal Cell Layer
Basal cell layer preserved (confirmed by immunohistochemistry)
Immunohistochemistry
34βE12: Positive (basal cells), p63: Positive (basal cells), AMACR: [Negative/Focally positive]
Associated Findings
[Benign prostatic hyperplasia/Chronic inflammation/Atrophy/No additional abnormalities]
Final Diagnosis
High-grade prostatic intraepithelial neoplasia (HGPIN), [multifocal/focal]
Recommendations
Repeat prostate biopsy recommended in 6-12 months due to increased cancer risk (approximately 35%)