High-grade prostatic intraepithelial neoplasia

High-grade prostatic intraepithelial neoplasia
Diagnosis in short
High-grade prostatic intraepithelial neoplasia. H&E stain.
Synonyms	prostatic intraepithelial neoplasia
LM	nuclear changes (hyperchromatic nuclei, nucleoli present, +/-increased NC ratio, mild-to-moderate nuclear enlargement), medium-to-large glands with the architecture of HGPIN (tufted, micropapillary, flat)
LM DDx	basal cell hyperplasia, prostatic adenocarcinoma, PIN-like prostatic ductal adenocarcinoma, atypical small acinar proliferation (biopsy only), atypical intraductal proliferation
IHC	AMACR +ve, basal cells present (p63 +ve, CK34betaE12 +ve)
Gross	not evident
Site	prostate gland
Associated Dx	prostate adenocarcinoma
Signs	none
Symptoms	none
Prevalence	common
Blood work	+/-PSA elevated
Radiology	not identifiable
Prognosis	benign
Clin. DDx	prostate carcinoma
Treatment	follow-up +/-re-biopsy

High-grade prostatic intraepithelial neoplasia, abbreviated as HGPIN, is considered the precursor for prostate carcinoma.

It may be referred to as prostatic intraepithelial neoplasia, abbreviated PIN.

General

• Thought to be a precursor lesion for prostate adenocarcinoma.
• Incidence ~5-8% on core biopsy.
• Multifocal HGPIN considered a risk for prostate cancer on re-biopsy.
  • A small focus of HGPIN does not appear to be associated with an increased risk for prostate cancer on re-biopsy at one year if the initial biopsy had 8 or more cores.
• Interrater variability is moderate (kappa ~ 0.45) for benign versus HGPIN.

Low-grade prostatic intraepithelial neoplasia:

• Should not be reported.
• Believed to be irrelevant biologically/clinically.
  • PIN not otherwise specified refers to HGPIN.
  • Low-grade PIN has the architecture of HGPIN but lacks the nuclear atypia.

HGPIN and cancer on follow-up biopsy

Prostate cancer on follow-up biopsy by number of HGPIN sites from Merrimen et al.:

Number of cores with HGPIN	Odds ratio of cancer on follow-up (95% CI)
0	1.00 (reference)
1	1.02 (0.73-1.40)
2	1.55 (1.08-2.21)
3	1.99 (1.16-3.40)
4	2.66 (1.10-6.40)

Gross

• Not evident on gross.

Microscopic

Features:

• Medium to large glands with architectural changes - see HGPIN architecture below.
  • Described as "epithelial hyperplasia".
• Diagnosed on basis of nuclear changes.
  • Hyperchromatic nuclei - key (low power) feature.
  • Nucleoli present - key (high power) feature.
  • Often increased NC ratio.
  • Nuclear enlargement - usually subtle/appreciated at high magnification only.
• Tinctorial changes of the cytoplasm - usually amphophilic (red) or basophilic (blue).

Notes:

• Nucleoli should be visible with the 20x objective.
  • If one uses the 40x objective... one over calls.
• May need IHC for cancer versus HGPIN.
• Nucleoli should be present in >= 10% of cells in a gland to call it HGPIN.
  • This criterium is not required by all pathologists.

DDx:

• Basal cell hyperplasia of the prostate.
• Intraductal carcinoma of the prostate.
• Prostatic adenocarcinoma - glands with HGPIN have two or more distinct cells layers.
  • PIN-like prostatic ductal adenocarcinoma - glands crowded.
• Benign prostate - HGPIN has nuclear changes.
  • Central zone typically has small nucleoli; however, the glands are larger.

HGPIN architecture

There are several forms:

• Flat - uncommon.
• Tufting - common.
• Micropapillary - common.

Notes:

• The architectural pattern is not thought to have any prognostic significance; however, it may be useful for differentiating it from benign prostate.
• "Cribriform HGPIN" previously existed; it is now classified as atypical intraductal proliferation.

Images

• 

  HGPIN - low mag. (WC/Nephron)

• 

  HGPIN - intermed. mag. (WC/Nephron)

• 

  HGPIN - high mag. (WC/Nephron)

IHC

• HGPIN: AMACR +ve, p63 +ve, HMWCK +ve.
• Cancer: AMACR +ve, p63 -ve, HMWCK -ve.
• Normal: AMACR -ve‡, p63 +ve, HMWCK +ve.

Note:

• ‡ May be positive in normal prostate.

Sign out

A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA;
- NEGATIVE FOR MALIGNANCY.

Mostly lower case

A.	Left Apex:
	-  Focal high grade prostatic intraepithelial neoplasia, chronic
	   inflammation 
	
B.	Left Middle Zone:
	-  Benign prostatic tissue 

C.	Left Base:
	-  Benign prostatic tissue 

D.	Right Apex:
	-  Benign prostatic tissue 

E.	Right Middle Zone:
	-  Benign prostatic tissue

F.	Right Base:
	-  Benign prostatic tissue

Colour seen in tissue cores at sign-out: green

Comment for many cores with HGPIN

If there is (isolated) HGPIN in more than 3 or 4 cores:

COMMENT:
As high-grade prostatic intraepithelial neoplasia is found in multiple cores, close 
follow-up is suggested, with a re-biopsy when indicated.

TURP

PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN), FOCAL.
- ACUTE AND CHRONIC INFLAMMATION.
- UROTHELIUM WITH MILD INFLAMMATION.
- NEGATIVE FOR MALIGNANCY.

See also

• Prostate gland.
• Prostate cancer.