High-grade prostatic intraepithelial neoplasia

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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, cribriform, flat)
LM DDx basal cell hyperplasia, prostatic adenocarcinoma, PIN-like prostatic ductal adenocarcinoma, atypical small acinar proliferation (biopsy only)
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.[1]
  • Multifocal HGPIN considered a risk for prostate cancer on re-biopsy.[2][3]
    • 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.[4]
  • Interrater variability is moderate (kappa ~ 0.45) for benign versus HGPIN.[5]

Low-grade prostatic intraepithelial neoplasia:

  • Should not be reported.[1]
  • 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.:[3]

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:[6][7]

  • 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.[8]
    • This criterium is not required by all pathologists.

DDx:

HGPIN architecture

There are several forms:[10][11]

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

Note:

  • The architectural pattern is not thought to have any prognostic significance; however, it may be useful for differentiating it from benign prostate.

Images

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.[12]

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

References

  1. 1.0 1.1 Epstein, JI.; Herawi, M. (Mar 2006). "Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care.". J Urol 175 (3 Pt 1): 820-34. doi:10.1016/S0022-5347(05)00337-X. PMID 16469560.
  2. Srigley, JR.; Merrimen, JL.; Jones, G.; Jamal, M. (Dec 2010). "Multifocal high-grade prostatic intraepithelial neoplasia is still a significant risk factor for adenocarcinoma.". Can Urol Assoc J 4 (6): 434. PMID 21191509.
  3. 3.0 3.1 Merrimen, JL.; Jones, G.; Walker, D.; Leung, CS.; Kapusta, LR.; Srigley, JR. (Aug 2009). "Multifocal high grade prostatic intraepithelial neoplasia is a significant risk factor for prostatic adenocarcinoma.". J Urol 182 (2): 485-90; discussion 490. doi:10.1016/j.juro.2009.04.016. PMID 19524976.
  4. Herawi, M.; Kahane, H.; Cavallo, C.; Epstein, JI. (Jan 2006). "Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled.". J Urol 175 (1): 121-4. doi:10.1016/S0022-5347(05)00064-9. PMID 16406886.
  5. Allam, CK.; Bostwick, DG.; Hayes, JA.; Upton, MP.; Wade, GG.; Domanowski, GF.; Klein, MA.; Boling, EA. et al. (Jul 1996). "Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma.". Mod Pathol 9 (7): 742-51. PMID 8832557.
  6. Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 3-56. ISBN 978-1931884280.
  7. Chin, AI.; Dave, DS.; Rajfer, J. (2007). "Is repeat biopsy for isolated high-grade prostatic intraepithelial neoplasia necessary?". Rev Urol 9 (3): 124-31. PMC 2002502. PMID 17934569. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2002502/.
  8. Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 3-55. ISBN 978-1931884280.
  9. Egevad, L. (May 2003). "Cytology of the central zone of the prostate.". Diagn Cytopathol 28 (5): 239-44. doi:10.1002/dc.10275. PMID 12722118.
  10. Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 380. ISBN 978-0781765275.
  11. Bostwick, DG.; Qian, J. (Mar 2004). "High-grade prostatic intraepithelial neoplasia.". Mod Pathol 17 (3): 360-79. doi:10.1038/modpathol.3800053. PMID 14739906. http://www.nature.com/modpathol/journal/v17/n3/pdf/3800053a.pdf.
  12. Ananthanarayanan, V.; Deaton, RJ.; Yang, XJ.; Pins, MR.; Gann, PH. (Jun 2005). "Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer.". Prostate 63 (4): 341-6. doi:10.1002/pros.20196. PMID 15602744.