PIN in routine surgical pathology terms usually refers to high-grade PIN (HGPIN)

Noninvasive neoplastic transformation of lining epithelium of preexisting prostatic ducts and acini, categorized into low-grade or high-grade PIN

PIN characterized by severe nuclear atypia (as in carcinoma) and varied, including more complex, architectural patterns

Seen in 19% of HGPIN intermingling with cancer foci vs. 48.5% for clinically localized PCa

HGPIN is present as isolated diagnosis in up to 16% of needle core biopsies (usually 5-6%) and 1-5% in transurethral resection specimens

Present in 80-100% of prostate glands harboring adenocarcinoma vs. 43% of age-matched controls

May be seen beginning in 3rd decade of life

Incidence increases with age, reaching up to 67% by 8th decade

Lesion is usually more diffuse and presents earlier in African-Americans compared to Caucasians

Debatable if it is the cause of increased PSA; difficult to exclude undetected coexistent PCa

No aggressive treatment (i.e., surgery, radiation) is warranted with diagnosis of HGPIN, unless concomitant adenocarcinoma is documented

HGPIN has been studied as potential marker &/or target for chemoprevention of PCa

Previously, diagnosis of HGPIN without PCa would prompt rebiopsy, as 50-60% of cases would have PCa in subsequent biopsy

Contemporary data, in era of extended sampling biopsy, has shown that median risk of cancer following diagnosis of HGPIN is around 21%

This risk is not significantly different from risk following benign diagnosis (around 19%)

Patients with multifocal HGPIN (i.e., > 3 cores), bilateral HGPIN, and that associated with ASAP have higher risk of harboring concomitant PCa, and should be more aggressively followed

Other clinical or pathologic parameters do not appear to identify patients with higher risk of harboring PCa

PCa is identified with higher frequency in or adjacent to quadrant where HGPIN was detected

However, up to 45% of PCas are found in another sextant

Incidence of detection of subsequent PCa in patients with isolated HGPIN increases when rebiopsy is performed at 1 and 3 years

On rebiopsy, sampling should include all sextants

Submit entire specimen for histologic evaluation or obtain deeper levels of block with HGPIN

Biopsy of peripheral zone may be an option, particularly in younger males

May consider deeper levels if extensive or associated with atypical small acinar proliferation (ASAP)

Hyperchromasia

Nuclear overlap

Enlarged relatively monomorphic nuclei

Prominent nucleoli (easily observed at 20x magnification)

Amphophilic cytoplasm

Diagnostic threshold varies as some individuals require all cells to be atypical and others require at least 10% of cells to have prominent nucleoli

Tufted (87%)

Micropapillary (85%)

Cribriform (32%)

Flat (25%)

Signet ring

Mucinous

Foamy

Inverted or “hobnail”

Small cell neuroendocrine

Luminal cytoplasmic blebs, epithelial arches, cellular trabecular epithelial bars, “Roman bridges,” partial gland involvement, and basal cell layer disruption with glandular budding

Proteinaceous secretions, corpora amylacea, and exfoliated cells of PIN

Uncommonly, microcalcifications, and crystalloids; comedonecrosis is extremely rare

Tufted or micropapillary pattern

Nuclear crowding, stratification, and irregular spacing

Mild nuclear enlargement, with inconspicuous to rare prominent nucleoli

Diagnostic reproducibility is very low and has questionable relationship to PCa

Should not be diagnosed in needle core biopsies, as management and significance is uncertain

Cellular proliferation within medium to large glands

Increased basophilia or amphophilia readily detected at low power

Hyperchromasia, nuclear membrane irregularity, macronucleoli

Greater reproducibility among pathologists and more established relationship to concomitant or subsequent adenocarcinoma