Prostate gland

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).

Prostate cancer is such a big topic it is dealt with in its own article.

Normal prostate gland

Anatomy

Divided into three zones:

1. Peripheral zone - posterior aspect, palpable with digit.
   • Classic location for cancer.
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.
  • 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:

• Benign prostate with corpora amylacea - low mag. (WC).
• Benign prostate with corpora amylacea - high mag. (WC).

IHC of normal prostate

Normal prostate:

• AMACR -ve (mark epithelial cells).
• CK5/6 +ve, 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:

• Resemble (mucinous) salivary glands.

DDx:

• Foamy gland carcinoma.
• Mucinous metaplasia of the prostate.

Images:

• Mucinous/serous salivary gland (duke.edu).
• Cowper gland (webpathology.com).

Stains

• Mucicarmine +ve.
• PAS-D +ve.

IHC

Features:

• 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.

Images:

• SV - showing fern-like architecture (WC).
• SV - looking vaguely like to prostate adenocarcinoma (WC).
• SV - looks a bit like prostate but lumina too big (WC).
• SV (udel.edu).

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.

Approach

• Know the common diagnoses well.
• Core biopsies - scan the slides with the 10x objective.

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.

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:

• 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:

• Prostatic nodular hyperplasia (WC).

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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:

• Prostate with acute inflammation (WC).

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:

• Prostate with chronic inflammation (WC).

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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 - the most commonly used is by Epstein & Hutchins.

Epstein & Hutchins classification

The groupings:

1. Non-specific.
   • No cause identified, usu. incidentally discovered.
   • Most common.
2. Post-TURP.
   • Palisading granuloma with necrotic core (histology similar to a rheumatoid nodule) +/- eosinophils.
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.
   • Usually associated with eosinophils.
   • Examples:
     1. Wegener granulomatosis.
     2. Churg-Strauss syndrome.

Microscopic

Features:

• Granulomas in the prostate - key feature.
  • Palisading granulomas with a necrotic core (similar to a rheumatoid nodule) consistent a prior TURP.
• +/-Eosinophils.

Images:

• Granulomatous inflammation of the prostate/bladder neck - low mag. (WC).
• Granulomatous inflammation of the prostate/bladder neck - high mag. (WC).

Stains

• GMS stain.
• Ziehl-Neelsen stain.

Note:

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

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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.
• AKA atrophy of the prostate gland.

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.
    • 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.
• 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:

• Atrophic prostate carcinoma.

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

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

Prostatic infarct

• AKA prostatic infarction.

General

• Rare < 0.1% of core biopsies.
• Can mimic cancer - urothelial carcinoma.
• Prostate usually large.

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:

• Urothelial carcinoma with squamous differentiation.

Image:

• Prostatic thrombosis (sciencephoto.com).

Basal cell hyperplasia of the prostate

• AKA basal cell hyperplasia.

General

• Benign lesion that can be misdiagnosed as cancer.

Microscopic

Features:

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

DDx:

• HGPIN.
• Prostatic adenocarcinoma.

Image:

• Basal cell hyperplasia of the prostate (webpathology.com).

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.
  • 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.

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:

• 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.
• Benign prostate - HPGIN has nuclear changes.

HGPIN architecture

There are several forms:

• 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:

• HGPIN - low mag. (WC).
• HGPIN - intermed. mag. (WC).
• HGPIN - high mag. (WC).

IHC

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

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

Atypical small acinar proliferation

• Abbreviated ASAP.
• AKA suspicious for carcinoma.
  • 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.
  • Analogous to ASCUS on a pap test.
• ASAP should be used sparingly.
  • One benchmark is < 3-5% of biopsies.
• Never diagnosed on excision, i.e. prostatectomy specimen.

Association with adenocarcinoma

• On subsequent biopsy - chance of finding adenocarcinoma is approximately 40%; this is higher than if there is high-grade prostatic intraepithelial neoplasia (HGPIN).

Management

• ASAP is considered an indication for re-biopsy; in one survey of urologists 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:

• Prostatic adenocarcinoma.

Prostate cancer

Main article: Prostate cancer

This is a big topic that is dealt with in its own article.

See also

• Urothelium.
• Genitourinary pathology.

External links

• CAP prostate check list - cap.org.
• CAP prostate protocol - cap.org.
• Gleason score quiz - Johns Hopkins Prostate Center.