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Prostate

Prostatic intraepithelial neoplasia (PIN)

High grade PIN


Reviewers: Monika Roychowdhury, M.D., (see Reviewers page)
Revised: 29 July 2012, last major update June 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Subtopics: general   cribriform   desquamating apoptotic   flat   foamy gland   inverted (hobnail)   micropapillary   mucinous   neuroendocrine   pleomorphic   signet ring   small cell   tufting

General
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● Incidence on needle biopsy is reported as 5% to 8% (71% to 83% in prostatectomy specimens)
● Present in 14% of patients in a community hospital study
● 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)
● In Americans less than 60 years old, more common in blacks vs. whites
● Does not cause elevated PSA
● If found on TURP specimen, should examine all submitted tissue for invasive adenocarcinoma
● 50% are aneuploid
● Patterns include apocrine, cribriform, flat, foamy gland, inverted (hobnail), micropapillary, mucinous, Paneth cell-like, pleomorphic, signet-ring cell, small cell neuroendocrine, tufting

Micro description
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● The hallmark distinguishing low-grade and high-grade PIN is the presence of prominent nucleoli
● Histologically characterised by prostate glands retaining a complete or partial basal cell layer lined by atypical cells with prominent nucleoli
● Low power diagnosis
● Usual patterns are micropapillary / cribriform (70%), flat / tufted (20%)
● Basophilic appearance at low power due to enlarged hyperchromatic nuclei and amphophilic cytoplasm
● May develop tall papillary tufts
● Frequently multicentric in prostatectomy specimens
● Identifiable on low power as glands with (a) papillary projections into lumina, (b) hyperchromasia, (c) enlarged nuclei, (d) pleomorphism, (e) stratification/crowding, (f) prominent nucleoli
● 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

Micro images
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Various images

High MW keratin

Positive stains
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● Basal cells - CK903, p63, CD10 (Hum Pathol 2003;34:450)
● Secretory 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-negative HGPIN

Molecular / Cytogenetics
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● 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

Differential diagnosis
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● Seminal vesicle glands with cribriform epithelium and no atypia: normal finding
● Clear cell cribriform hyperplasia: clear cytoplasm, benign nuclei, no/small nucleoli, prominent basal cell layer
● 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)

Additional references
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Cancer Control 2010;17:214


Cribriform patterns

Micro images
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Various images


Desquamating apoptotic pattern

Micro description
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● Desquamating cells containing apoptotic nuclear material and coalesce in the gland lumens to form basophilic intraluminal masses (Hum Pathol 2011;42:892)

Micro images
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Glands are large and complex, many containing basophilic intraluminal apoptotic cells and cellular remnants; inset shows complex epithelial lining of tall columnar cells with malignant nuclear features


34&betaE12 staining shows incomplete layer of basal cells; detached apoptotic cells coalesce centrally; terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) (upper inset) confirms apoptotic nuclei within epithelium and detached cells; occasional glands contain necrotic intraluminal cell material suggestive of early comedonecrosis (lower inset)


Gland with smooth rounded outline is filled with malignant intraluminal cells growing in dense cribriform pattern typical of HG PIN, which is focally positive for AE1/AE3 (inset)


Flat pattern

Micro images
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Various images


Foamy gland pattern

Micro description
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● Pale/foamy cells with voluminous xanthomatous cytoplasm, forming solid and cribriform patterns

Micro images
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Various images


Inverted (hobnail) pattern

General
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● Localized to peripheral zone (Am J Surg Pathol 2001;25:1534)
● Associated with concurrent prostatic adenocarcinoma in 50% of cases

Micro description
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● Polarization of enlarged secretory cell nuclei toward the glandular lumen
● Merges with typical micropapillary–tufted HGPIN
● Often less prominent nucleoli than adjacent noninverted secretory cell nuclei

Additional references
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Am J Surg Pathol 2003;27:772


Micropapillary pattern

Micro images
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Various images

Additional references
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Am J Surg Pathol 2001;25:1079


Mucinous

Micro description
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● Mucinous distension of glands with flat epithelial lining, blue mucinous secretions

Micro images
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Figure 8A/8B - mucinous pattern

Positive stains
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● PAS, Alcian blue (Am J Surg Pathol 1997;21:1215)


Neuroendocrine

Micro images
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Neuroendocrine cells (Paneth cell-like change)


Pleomorphic pattern

Micro description
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● Pleomorphic nuclei, although nucleoli may not be prominent

Additional reference
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Am J Surg Pathol 2001;25:1079


Signet ring pattern

Micro description
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● Associated with primary signet ring cell carcinoma

Positive stains
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● PSA

Negative stains
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● Mucin negative (Am J Surg Pathol 1997;21:1215)


Small cell pattern

General
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● Associated with primary small cell carcinoma

Micro images
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Various images

Positive stains
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● Chromogranin, synaptophysin, neuron-specific enolase (Am J Surg Pathol 1997;21:1215)


Tufting pattern

Micro images
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Various images

End of Prostate > Prostatic intraepithelial neoplasia (PIN) > High grade PIN


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