Prostate gland & seminal vesicles

Atypical / intraductal lesions

HGPIN with adjacent atypical glands



Last author update: 7 September 2022
Last staff update: 7 September 2022

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PubMed Search: High grade prostatic intraepithelial neoplasia with adjacent atypical glands

Aliaksandr Aksionau, M.D.
Y. Albert Yeh, M.D., Ph.D.
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Cite this page: Aksionau A, Yeh YA. HGPIN with adjacent atypical glands. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/prostatePINATYP.html. Accessed December 6th, 2022.
Definition / general
Essential features
  • Single or a few small atypical glands located within 0.01 - 0.4 mm of adjacent HGPIN (Hum Pathol 2001;32:389)
  • Adjacent atypical glands stained positive (focal or patchy) on p63 or CK903 immunohistochemical stains
Terminology
ICD coding
  • ICD-O: 8148/2 - glandular intraepithelial neoplasia, grade III
  • ICD-10:
    • N42.31 - prostatic intraepithelial neoplasia
    • D07.5 - grade III, severe dysplasia
  • ICD-11: XH5C49 - prostatic intraepithelial neoplasia, grade III
Epidemiology
  • More commonly arises in the peripheral zone
  • Incidence of HGPIN with adjacent atypical glands (2.5%) is lower than that of HGPIN alone (4.3%) (Urology 2001;57:296)
Sites
Pathophysiology
  • Hypothesis of proliferative inflammatory atrophy as a precursor to HGPIN and prostate cancer (N Engl J Med 2003;349:366)
  • Focal epithelial atrophy occurs in prostatic glands
  • Chronic inflammatory cells infiltrate immediately adjacent to the areas of glandular atrophy
  • HGPIN and localized prostate carcinoma develops as a result of DNA methylation and inactivation of DNA repair genes including GSTP1 and MGMT
  • Reduced expression of PTEN, NKX3.1 and p27 is involved in prostate cancer progression (Nat Rev Urol 2018;15:222)
Etiology
  • Gene mutation
    • Germline mutations in familial prostate cancer: ELA2 (HPC2), MSR, RNASEL
    • Somatic mutations: TP53, PTEN, AR, ZFHX3, RB1, APC, MLL2, OR5L1, CDK12, ATM, FOXA1, EZH2 (Nature 2012;487;239, Genes Dev 2018;32:1105)
  • Gene fusion
  • WNT signaling and beta catenin
    • Increased level of CTNNB1 detected by immunohistochemical staining in prostate cancer
  • DNA hypermethylation (Biochim Biophys Acta 2004;1704:87)
    • Invasion: GSTP1, MGMT, RASSF1A, RARβ2, CDH1 (E-cadherin), CAV1 (caveolin-1), LAMA3, LAMB3, LAMC2
    • Metastasis: APC, CDH1 (E-cadherin), CD44
  • Histone modification: MLL2 mutation
  • MicroRNA upregulation: overexpression of DICER, a key gene involved in biosynthesis of miRNA
Diagrams / tables

Images hosted on other servers:
Prostate cancer pathogenesis

Prostate cancer pathogenesis

Clinical features
Diagnosis
  • May present with dysuria or hematuria if there is a coexisting prostatic nodule or urinary tract infection
  • Solid, firm nodule on digital rectal examination (DRE) may be detected
  • A few atypical glands immediately adjacent to HGPIN is present on microscopic examination of the prostatic samples obtained from biopsy, TURP or prostatectomy (Urology 2001;57:296, JAMA 2017;317:2532)
Laboratory
Prognostic factors
Treatment
  • No definitive treatment for ASAP and HGPIN
  • For ASAP and multifocal (> 2 sites) HGPIN, rebiopsy within 6 months; includes sampling more from the previous affected and adjacent areas
  • For focal HGPIN, close follow up with PSA and DRE within 6 - 24 months; consider other testing, including free PSA, 4Kscore, PHI, PCA3 or ConfirmMDx (J Natl Compr Canc Netw 2016;14:509)
Microscopic (histologic) description
  • Single or a few small atypical glands located within 0.01 - 0.4 mm of adjacent HGPIN (Hum Pathol 2001;32:389)
  • The lining epithelial cells of HGPIN show high grade nuclei with nuclear enlargement, hyperchromasia and prominent nucleoli
  • A layer of horizontally lined basal cells presents in the HGPIN
  • Epithelial cells of the atypical glands show nuclear enlargement, prominent nucleoli and amphophilic cytoplasm, mimicking the cytologic features of HGPIN
Microscopic (histologic) images

Contributed by Y. Albert Yeh, M.D., Ph.D. and Nicholas P. Reder, M.D., M.P.H.
HGPIN with atypical glands

HGPIN with atypical glands

Atypical gland with basal cells

Atypical gland with basal cells

Single atypical gland

Single atypical gland

2 atypical glands

2 atypical glands

Atypical gland in 2 HGPINs

Atypical gland in 2 HGPINs

Atypical cytologic features

Atypical cytologic features


Small atypical glands adjacent to larger HGPIN glands

PIN4

PIN4

Negative stains
Sample pathology report
  • Prostate, needle biopsy:
    • Atypical small acinar proliferation (ASAP)
    • High grade prostatic intraepithelial neoplasia (see comment)
    • Comment: The prostatic needle biopsy shows prostatic tissue with high grade intraepithelial neoplasia (HGPIN). Immediately adjacent to the HGPIN are 3 well formed small glands composed of cells with enlarged nuclei and prominent nucleoli, mimicking the cellular features of HGPIN. Immunohistochemical stains p63 and CK903 show focal positive staining in the small atypical glands and continuous positive staining in HGPIN. AMACR immunomarker staining is positive in both lesions. These features are consistent with HGPIN with adjacent atypical glands (HGPIN and ASAP). It has been shown that the cancer detection rate of HGPIN and ASAP is higher than that of HGPIN alone. Repeat biopsy within 6 months is advised (Am J Surg Pathol 2005;29:1201).
Differential diagnosis
  • Acinar adenocarcinoma (Hum Pathol 2001;32:389):
    • More than a few (many) or numerous small malignant glands infiltrating the stroma
    • Located at either > or < 0.4 mm from HGPIN
    • Negative staining of immunomarkers for basal cells (p63, CK5/6 or CK903)
  • HGPIN with tangential sectioning or outpouching of glands (BJU Int 2007;99:780):
    • Immediately adjacent to HGPIN
    • Cellular features and immunostaining pattern mimicking HGPIN (continuous or patchy staining pattern with basal cell immunomarkers)
    • May have connection with HGPIN on deeper levels of tissue sectioning
Board review style question #1

A 68 year old man presented with dysuria. A firm nodule was detected on digital rectal examination. PSA level was 6.4 ng/mL. Prostatic needle biopsy followed by microscopic examination was performed. The photomicrograph is shown in the image above. Immunohistochemical stains are performed. The large and small glands show patchy positive staining with p63 and CK903. AMACR immunomarker is positive in the large and small glands. What is the best interpretation?

  1. High grade prostatic intraepithelial neoplasia
  2. High grade prostatic intraepithelial neoplasia with atypical glands
  3. Prostatic adenocarcinoma, Gleason 3+3=6
  4. Prostatic intraductal adenocarcinoma
Board review style answer #1
B. High grade prostatic intraepithelial neoplasia with atypical glands

Comment Here

Reference: HGPIN with adjacent atypical glands
Board review style question #2
What is the best clinical management of high grade prostatic intraepithelial neoplasia with adjacent atypical glands?

  1. Close follow up with PSA and digital rectal examination within 6 months
  2. Close follow up with PSA only within 6 months
  3. Rebiopsy including increased sampling from previous affected and adjacent areas within 6 months
  4. Rebiopsy within 6 to 12 months
Board review style answer #2
C. Rebiopsy including increased sampling from previous affected and adjacent areas within 6 months

Comment Here

Reference: HGPIN with adjacent atypical glands
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