Prostate gland

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The prostate gland adds juice to the sperm. In old men it creates lotsa problems... nodular hyperplasia (commonly called BPH or benign prostatic hyperplasia) and cancer (adenocarcinoma).

Normal prostate gland

Anatomy

Divided into three zones:[1]

  1. Peripheral zone - posterior aspect, palpable with digit.
  2. Central zone - considered resistant to disease.
  3. Transition zone - usual location for nodular hyperplasia.

Histology

  • Glands have two cell layers (similar to glands in breast).
    • Second cell layer may be difficult to see (like in breast).
  • Epithelium in glands is "folded" or "tufted".
    • Very important - helps on differentiate from Gleason pattern 3.
  • Luminal epithelium often clear cytoplasm.
  • Single nucleus.

Benign normal:

  • Corpora amylacea.
    • Round/ovoid-eosinophilic bodies -- with laminations (layered appearance).
    • In gland lumina.
    • Usually in benign glands - but cannot be used to exclude cancer.[2]
    • Very common.
    • These should be differentiated from eosinophilic proteinaceous debris - which is associated with cancer.

Negatives:

  • No nucleoli present (if you see nuclei think: cancer, HGPIN, reactive changes, basal cell hyperplasia).
  • No mitoses - these are uncommon... even in high grade prostate cancer.

Notes:

  • Tufted epithelium is a strong indicator of benignancy; however two uncommon prostate cancer typically have tufted epithelium:
    • Pseudohyperplastic adenocarcinoma.
    • Foamy gland carcinoma.

Images:

IHC of normal prostate

Normal prostate:

  • AMACR -ve (mark epithelial cells).
  • CK5/6 +ve,[3] p63 +ve, HMWCK +ve (mark basal cells).
  • PSA (prostate-specific antigen) +ve, PSAP (prostatic-specific acid phosphatase) +ve.

Other accessory glands

Bulbourethral gland

  • AKA Cowper's gland.

General

  • Mucinous glands at the apex of the prostate.

Microscopic

Features:[4]

DDx:

Images:

Stains

IHC

Features:[4]

  • PSAP -ve.
  • PSA +ve.
  • HMWCK +ve.

Seminal vesicles

  • Fern-like architecture - epithelial component clustered closely, looks like it connects.
    • Epithelium surrounded by a thick layer of muscle (>10 cells across ~80 microns).
  • Lipofuscin (coarse cytoplasmic yellow granules approximately 1-2 micrometers) - key feature.
  • Nucleoli - common.
  • Nuclear inclusions - common.

Notes:

  • The ejaculatory ducts have the same epithelium as the seminal vesicles.[5]

Images:

Specimens

  • Prostate core biopsy - done transrectal.
  • Prostate chips (from a transurethral resection of the prostate, abbreviated TURP) - usu. done for nodular hyperplasia of the prostate gland; may be done in the context of obstructing cancer.
  • Radical prostatectomy - includes the seminal vesicles.
  • Radical cystoprostatectomy - includes the urinary bladder and seminal vesicles.[6]

Common diagnoses

  • Benign.
    • Atrophy - may resemble adenocarcinoma - typically not reported.
    • Adenosis - may resemble adenocarcinoma - typically not reported.
  • Prostate adenocarcinoma.
    • Most common Grade is 3+3=6.
  • HGPIN (high-grade prostatic intraepithelial neoplasia) - prostate adenocarcinoma precursor lesion.
  • ASAP (atypical small acinar proliferation) - used if you have a few abnormal appearing glands... but can't decide between prostate adenocarcinoma & benign.
  • Chronic inflammation.
  • Acute inflammation - can result in an elevated PSA and may have prompted the biopsy you're looking at.
  • Nodular hyperplasia of the prostate; AKA benign prostatic hypertrophy (BPH).
    • Not diagnosed on needle biopsies.
    • BPH is technically incorrect -- the process is a hyperplasia.
      • Hyperplasia = proliferation of cells, hypertrophy = enlargement of cells.
        • How to remember? A. Prostate... hyperPlasia.

Clinical history

  • PSA (serum).
    • >10 ng/mL worrisome for prostate cancer.
    • Normal is age dependent - increases with age, usu. cut-off ~ 4 ng/mL.
  • HIFU = High Intensity Focused Ultrasound - an ablation procedure for prostate cancer.[7]

Specific conditions

Prostatic nodular hyperplasia

  • AKA nodular hyperplasia of the prostate.
  • AKA benign prostatic hyperplasia (abbreviated BPH).
  • AKA benign prostatic hypertrophy.
    • This is a misnomer. It is not a hypertrophy.

General

  • Very common.
  • Incidence increases with age.

Clinical - mnemonic I WISH 2p:[8]

  • Intermittency.
  • Weak stream.
  • Incomplete emptying.
  • Straining.
  • Hesitancy.
  • Post-void dribbling.
  • Prolonged voiding.

Treatment:

  • Medications.
  • Transurethral resection of the prostate (TURP).

Microscopic

Features:

  • Stromal and/or glandular hyperplasia.

Note:

  • Should not be diagnosed on core biopsy!

Image:

Sign out

PROSTATE GLAND, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- BENIGN PROSTATIC TISSUE WITH GLANDULAR AND STROMAL PROLIFERATION.

Acute inflammation

General

  • A may lead to an increase in the PSA and prompt biopsy.

Microscopic

Features:

  • Neutrophils within the glands, between the epithelial cells or within the stroma - key feature.

Note:

  • "Prostatitis" is considered a clinical diagnosis.
    • Cases are signed-out as "acute inflammation".
      • Some pathologists do not comment on the presence (or absence) of inflammation.

Image:

Chronic inflammation not otherwise specified

General

  • Common.
  • Non-specific finding.
  • Etiology usually not apparent on histomorphology.

Microscopic

Features:

  • Lymphocytes within the glands, between the epithelial cells or within the stroma - key feature.

Image:

Sign out

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION. 
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION. 

Note:

  • Opinion is divided on whether this finding should be reported.
    • Advocates for reporting inflammation say "[i]t is just reporting what you see and may explain the bump in PSA."
    • Naysayers opine that "[i]t may provide false assurance that no cancer is present."

Granulomatous prostatitis

  • AKA prostatic granuloma.
  • AKA prostate gland granuloma.

General

  • Common.
  • Usually secondary to BCG treatment of bladder cancer.
  • Several classifications exist[9] - the most commonly used is by Epstein & Hutchins.

Epstein & Hutchins classification

The groupings:[10]

  1. Non-specific.
    • No cause identified, usu. incidentally discovered.
    • Most common.
  2. Post-TURP.
  3. Specific.
    • Identifiable infectious agent, usu. BCG (in the context of treating bladder cancer), rarely tuberculosis and even more rarely various fungi and syphilis.
  4. Allergic granulomatous prostatitis.

Microscopic

Features:

  • Granulomas in the prostate - key feature.
  • +/-Eosinophils.

Images:

Stains

Note:

  • Stains are indicated when there is a suspicion of an infective etiology based on histomorphology or clinical information (e.g. immunosuppression).

Sign out

PROSTATE GLAND, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- BENIGN PROSTATIC TISSUE WITH GLANDULAR AND STROMAL PROLIFERATION.
- PALISADING GRANULOMA WITH NECROTIC CORE, SEE COMMENT.

COMMENT:
This is morphologically consistent with a post-TURP granuloma.

Atrophy of the prostate

  • AKA atrophy.
  • AKA prostatic atrophy.

General

  • Small glands (may mimic Gleason score 3 pattern).

Microscopic

Features:

  • Glands often have a jagged edges/prows (in cancer the glands tend to have round edges) - key feature.
    • Prow = forward most part of a ship's bow that cuts through the water.[13]
      • You may have come across prow in the context of breast cancer, i.e. tubular carcinoma.
  • Gland density is usually lower than in prostate carcinoma, i.e. glands are not back-to-back - key feature.
  • Atrophic glands are often hyperchromatic.[14]
  • Scant cytoplasm - usually.

Negatives:

  • Nuclei like normal, i.e. nucleoli uncommon.
  • Should have two cell layers, i.e. epithelial and myoepithelial (may be difficult to see).

Notes:

  • Atrophic glands may be scattered with non-atrophic ones.
  • IHC may be misleading - basal cell loss.

DDx:

Atrophy versus cancer

Histologic feature Atrophy Cancer
Glandular architecture/
arrangement
angulated glands, may
look like they originate
from one large duct
round glands,
often back-to-back
Nuclear
hyperchromasia
marked moderate
Cytoplasm scant/minimal moderate, may
be amphophilic
Basal cells may be visible absent
Nucleoli absent present
Secretions in
glands
no yes - eosinophilic
or blue

Sign out

Generally, this finding is not reported; it is considered a normal finding.

Prostatic infarct

General

Microscopic

Features:

  • Classic findings of necrosis:
    • Karyolysis (loss of nuclei), karyorrhexis (frag. of nuclei), pyknosis (small shrunken nuclei).
  • +/-Squamous metaplasia of prostate gland epithelium.

Notes:

  • Corpora amylacea - help... call it benign.
  • Glands maintain normal spacing.

DDx:

Image:

Basal cell hyperplasia of the prostate

General

  • Benign lesion that can be misdiagnosed as cancer.[16]

Microscopic

Features:[17]

  • Low power gland architecture near normal.[18][19]
    • Glands not as small as cancer.
    • Folds in gland lumina.
  • No hyperchromasia.
  • Two cell populations (as in normal prostate glands).
  • May have nucleoli.

DDx:

Image:

High-grade prostatic intraepithelial neoplasia

  • Abbreviated as HGPIN.
  • May be referred to as prostatic intraepithelial neoplasia, abbreviated PIN.

General

  • Thought to be a precursor lesion for prostate adenocarcinoma.
    • Multifocal HGPIN considered a risk for prostate cancer on re-biopsy.[20]
    • Small a small focus of HGPIN does not appear to be associated with increased risk for prostate cancer on re-biopsy at one year if the initial biopsy had 8 or more cores.[21]

Low-grade prostatic intraepithelial neoplasia:

  • Not reported and generally 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.

Microscopic

Features:

  • Architectural changes - see below, usually tufting.
  • Diagnosed on basis of nuclear changes.
    • Hyperchromatic nuclei - key (low power) feature.
    • Nucleoli present - key (high power) feature.
    • Often increased N/C ratio.
    • Nuclear enlargement.
  • Usually epithelial hyperplasia.

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.

DDx:

HGPIN architecture

There are several forms:[22][23]

  • 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.

Sign out

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

Atypical small acinar proliferation

  • Abbreviated ASAP.
  • AKA suspicious for carcinoma.[24]
    • ASAP is preferred as it does not contain the word carcinoma and, thus, cannot be misread as carcinoma, i.e. positive for malignancy.

General

  • It is a waffle diagnosis, i.e. it is not considered an entity with a distinct pathobiology.[25]
    • Analogous to ASCUS on a pap test.
  • ASAP should be used sparingly.
    • One benchmark is < 3-5% of biopsies.[26]
  • Never diagnosed on excision, i.e. prostatectomy specimen.

Association with adenocarcinoma

Management

  • ASAP is considered an indication for re-biopsy;[28] in one survey of urologists[29] 41/42 (~98%) of respondents considered it a sufficient reason to re-biopsy.

Microscopic

Features:

  • Atypical appearing acini.
  • Limited extent, e.g. 2-3 glands.

Notes:

  • IHC not contributory.
  • Deeper cuts didn't yield anything - important.

DDx:

Intraductal carcinoma of the prostate

  • AKA intraductal carcinoma.
  • AKA intraductal prostate carcinoma.

General

  • Associated with a poor prognosis.[30]
  • Strong association with aggressive invasive carcinomas on prostatectomy when identified in isolation on biopsy.[31]

Microscopic

Features:

  • Malignant cells in glands with basal cells - key feature.
    • Two cell populations:
      1. Obviously malignant cells with enlarged nuclei, granular chromatin, hyperchromasia and nucleoli.
      2. Cells with pale cytoplasm and smaller nuclei.

DDx:

IHC

Features - basal cells present:

  • HMWK +ve.

Unusual forms of prostate cancer

Prostatic ductal adenocarcinoma

  • AKA ductal adenocarcinoma of the prostate.
  • AKA prostatic adenocarcinoma, large duct type.

General

  • Sometimes it is referred to as endometrioid or endometrial adenocarcinoma; both terms are discouraged.[32]
  • Not completely uncontroversial - may represent acinar adenocarcinoma with periurethral ducts involvement.[33]
  • More aggressive than conventional (acinar) prostate carcinoma.

Microscopic

Features:[34]

  • Pseudostratified (crowded appearing) columnar (or cigar-shaped) nuclei - key feature.
  • Variable architecture:
    • Papillary.
    • Cribriform.
    • Single gland (large glands).
    • Endometrioid - vaguely looks like endometrial carcinoma (with back-to-back glands).

Notes:

  • Usually seen in association with conventional (acinar) prostate adenocarcinoma.
    • Proportion of ductal component should be quantified:
      • <10% ductal component of no prognostic significance.[35]

Images:

IHC

Features:[36]

  • p53 +ve in ~ 75% of cases.
  • Ki-67 high in ~ 70% of cases.
  • Chromogranin A +ve (cytoplasm) in ~ 70% of cases.

Others:[37]

  • PSA +ve.

PIN-like prostatic ductal adenocarcinoma

General

Microscopic

Features:[38]

  • Stratified malignant epithelium.

Note:

  • Vaguely similar to a tubular adenoma of the colon.

DDx:

Image:

Foamy gland carcinoma

General

  • Rare.

Microscopic

Features:

  • Tufted glandular border.
  • Abundant eosinophilic (or hyperchromatic) cytoplasm - key feature.
  • Gland size larger than "typical" prostate cancer.

Image: Foamy gland carcinoma (nature.com).

Atrophic prostate carcinoma

  • AKA atrophic carcinoma.

General

  • Uncommon.

Note:

  • An atrophic component in prostate cancer is common; one study identified it in ~15% of cases.[40]

Microscopic

Features:

  • Scant cytoplasm.
  • Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).
  • Increased gland density.

DDx:

Image: Atrophic carcinoma (nature.com).

Mucinous prostate carcinoma

General

  • Rare.

Microscopic

Features:

  • Cytologically malignant cells floating in mucin.
  • > 25% of tumour mucinous.[41]
    • One study suggests >= 25%.[42]

DDx:

Notes:

Pseudohyperplastic prostatic adenocarcinoma

General

  • Rare.

Microscopic

Features:[43][44]

  • Medium to large glands with an atypical morphology - key low power feature:
    • Papillary or pseudopapillary infoldings, luminal undulations, branching or cystic dilatation.
  • Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).

Image: Pseudohyperplastic prostatic adenocarcinoma (nature.com).

Notes:

  • Usually associated with conventional (acinar) prostate adenocarcinoma.
  • Pale abundant cytoplasm - similar to normal prostate.

Prostatic signet ring cell carcinoma

General

  • Very rare - 9 cases in a series of 29,783 prostate cancer cases.[45]
  • Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.[45]

Microscopic

Features:

  • Signet ring cells - see basics article.

Image:

Sarcomatoid prostate carcinoma

  • AKA carcinosarcoma.

General

  • Rare.

Microscopic

Features:[46]

IHC

Features - typical:[46]

  • PSA +ve.
  • Keratin +ve.

Small cell carcinoma of the prostate gland

General

  • Rare.

Microscopic

Features:

  • Nuclear moulding.
  • Stippled chromatin.
  • High NC ratio.
  • Small cells.

Notes:

Adenoid cystic/basal cell carcinoma of the prostate

  • Abbreviated ACBCC.

General

  • Rare.
  • Typically indolent - may be aggressive.[47]

Microscopic

Features:

Images:

IHC

  • HER2/neu +ve (strong).[48]

See also

References

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  2. Christian JD, Lamm TC, Morrow JF, Bostwick DG (January 2005). "Corpora amylacea in adenocarcinoma of the prostate: incidence and histology within needle core biopsies". Mod. Pathol. 18 (1): 36–9. doi:10.1038/modpathol.3800250.
  3. Trpkov, K.; Bartczak-McKay, J.; Yilmaz, A. (Aug 2009). "Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens.". Am J Clin Pathol 132 (2): 211-20; quiz 307. doi:10.1309/AJCPGFJP83IXZEUR. PMID 19605815.
  4. 4.0 4.1 Cina, SJ.; Silberman, MA.; Kahane, H.; Epstein, JI. (May 1997). "Diagnosis of Cowper's glands on prostate needle biopsy.". Am J Surg Pathol 21 (5): 550-5. PMID 9158679.
  5. Leroy X, Ballereau C, Villers A, et al. (April 2003). "MUC6 is a marker of seminal vesicle-ejaculatory duct epithelium and is useful for the differential diagnosis with prostate adenocarcinoma". Am. J. Surg. Pathol. 27 (4): 519–21. PMID 12657938.
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  8. TN06 U5
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  14. SN. June 3, 2009.
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  21. 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.
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  26. THvdK. 19 June 2010.
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  35. Amin, A.; Epstein, JI. (Apr 2011). "Pathologic stage of prostatic ductal adenocarcinoma at radical prostatectomy: effect of percentage of the ductal component and associated grade of acinar adenocarcinoma.". Am J Surg Pathol 35 (4): 615-9. doi:10.1097/PAS.0b013e31820eb25b. PMID 21383610.
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  41. Grignon DJ (March 2004). "Unusual subtypes of prostate cancer". Mod. Pathol. 17 (3): 316–27. doi:10.1038/modpathol.3800052. PMID 14976541.
  42. Osunkoya AO, Nielsen ME, Epstein JI (March 2008). "Prognosis of mucinous adenocarcinoma of the prostate treated by radical prostatectomy: a study of 47 cases". Am. J. Surg. Pathol. 32 (3): 468–72. doi:10.1097/PAS.0b013e3181589f72. PMID 18300802.
  43. Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 77. ISBN 978-0443066771.
  44. Arista-Nasr J, Martinez-Benitez B, Valdes S, Hernández M, Bornstein-Quevedo L (2003). "Pseudohyperplastic prostatic adenocarcinoma in transurethral resections of the prostate". Pathol. Oncol. Res. 9 (4): 232–5. doi:PAOR.2003.9.4.0232. PMID 14688829.
  45. 45.0 45.1 Warner, JN.; Nakamura, LY.; Pacelli, A.; Humphreys, MR.; Castle, EP. (Dec 2010). "Primary signet ring cell carcinoma of the prostate.". Mayo Clin Proc 85 (12): 1130-6. doi:10.4065/mcp.2010.0463. PMID 21123640.
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