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).

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

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:

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.

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Staining slightly abnormal - morphology not definitely abnormal

COMMENT:
Very focal AMACR staining is seen; this is interpreted as negative, in the
context of no definite cytologic changes.  The basal cells appear to be 
preserved in all of the tissue sampled.

Compatible with previous biopsy

COMMENT:
Siderophages are seen in several cores; this is compatible with the history 
of a previous biopsy.

Other accessory glands

Bulbourethral gland

  • AKA Cowper's gland.

General

  • Mucinous glands at the apex of the prostate.

Microscopic

Features:[4]

  • Lobular glands with abundant pale cytoplasm.
  • Often assocatiated with skeletal muscle.[5]

DDx:

Images:

Stains

IHC

Features:[4]

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

Seminal vesicles

General

  • Seen in radical prostatectomies and occasionally in core biopsies.

Microscopic

  • 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.[6]

Notes:

  • The ejaculatory ducts have the same epithelium as the seminal vesicles.[7]

Images

www:

IHC

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B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
- BENIGN SEMINAL VESICLE/EJACULATORY DUCT.

Specimens

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.[12]

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.

Acute inflammation of the prostate gland

Prostate gland
External resources
EHVSC 10176
  • AKA prostate gland with acute inflammation.

General

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

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.

Microscopic

Features:

  • Neutrophils within the glands, between the epithelial cells or within the stroma - key feature.
  • +/-Chronic inflammation (lymphocytes) within the surrounding stroma.

DDx:

Image

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G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE INFLAMMATION. 
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE AND CHRONIC INFLAMMATION. 

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.

Notes:

  • Rare scattered lymphocytes are common, especially in the central portion of the gland.
  • "Focal" one field with a 2.2 mm diameter involved.

Image

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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

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.[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

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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 nuclear hyperchromasia.
  • Two cell populations (as in normal prostate glands).
  • Basal cells may have nucleoli.

DDx:

Images

www:

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  • Usually not reported.

High-grade prostatic intraepithelial neoplasia

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

Atypical small acinar proliferation

  • Abbreviated ASAP.
  • AKA suspicious for carcinoma.[20]
    • 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.[21]
    • Analogous to ASCUS on a pap test.
  • ASAP should be used sparingly.
    • One benchmark is < 3-5% of biopsies.[22]
  • Never diagnosed on excision, i.e. prostatectomy specimen.

Association with adenocarcinoma

Management

  • ASAP is considered an indication for re-biopsy;[24] in one survey of urologists[25] 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:

Prostate cancer

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

See also

References

  1. McNeal, JE. (Aug 1988). "Normal histology of the prostate.". Am J Surg Pathol 12 (8): 619-33. PMID 2456702.
  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. URL: http://webpathology.com/image.asp?case=21&n=4. Accessed on: 3 June 2013.
  6. URL: http://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/benign-vs-carcinoma.html. Accessed on: 10 January 2013.
  7. 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.
  8. Itami, Y.; Nagai, Y.; Kobayashi, Y.; Shimizu, N.; Yamamoto, Y.; Minami, T.; Hayashi, T.; Nozawa, M. et al. (Jul 2012). "[A case of prostatic cancer with a low PSA level accompanied with cystic formation requiring differentiation from adenocarcinoma of the seminal vesicle].". Hinyokika Kiyo 58 (7): 349-53. PMID 22895132.
  9. 9.0 9.1 Tarján, M.; Ottlecz, I.; Tot, T. (Jan 2009). "Primary adenocarcinoma of the seminal vesicle.". Indian J Urol 25 (1): 143-5. doi:10.4103/0970-1591.45557. PMID 19468449.
  10. 10.0 10.1 10.2 10.3 Terada, T. (2011). "Monstrous epithelial cell clusters in the seminal vesicle.". Int J Clin Exp Pathol 4 (7): 727-30. PMID 22076175.
  11. URL: http://www.cancer.gov/dictionary?cdrid=446218. Accessed on: 23 February 2012.
  12. URL: http://www.internationalhifu.com/what-is-hifu-mainmenu-132.html. Accessed on: 15 June 2010.
  13. http://en.wikipedia.org/wiki/Prow
  14. SN. June 3, 2009.
  15. 15.0 15.1 Milord, RA.; Kahane, H.; Epstein, JI. (Oct 2000). "Infarct of the prostate gland: experience on needle biopsy specimens.". Am J Surg Pathol 24 (10): 1378-84. PMID 11023099.
  16. Cleary, KR.; Choi, HY.; Ayala, AG. (Dec 1983). "Basal cell hyperplasia of the prostate.". Am J Clin Pathol 80 (6): 850-4. PMID 6195916.
  17. URL: http://pathologyoutlines.com/prostate.html#bch. Accessed on: 28 June 2010.
  18. URL: http://www.nature.com/modpathol/journal/v16/n6/fig_tab/3880810f1.html. Accessed on: 28 June 2010.
  19. URL: http://www.nature.com/modpathol/journal/v16/n6/fig_tab/3880810f2.html. Accessed on: 28 June 2010.
  20. THvdK. 19 June 2010.
  21. Flury SC, Galgano MT, Mills SE, Smolkin ME, Theodorescu D (January 2007). "Atypical small acinar proliferation: biopsy artefact or distinct pathological entity". BJU International 99 (4): 780-5. PMID 17378841. http://www3.interscience.wiley.com/journal/118508438/abstract.
  22. THvdK. 19 June 2010.
  23. Leite KR, Camara-Lopes LH, Cury J, Dall'oglio MF, Sañudo A, Srougi M (June 2008). "Prostate cancer detection at rebiopsy after an initial benign diagnosis: results using sextant extended prostate biopsy". Clinics 63 (3): 339–42. PMID 18568243. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300009&lng=en&nrm=iso&tlng=en.
  24. Bostwick DG, Meiers I (July 2006). "Atypical small acinar proliferation in the prostate: clinical significance in 2006". Arch. Pathol. Lab. Med. 130 (7): 952–7. PMID 16831049. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=130&page=952.
  25. Rubin MA, Bismar TA, Curtis S, Montie JE (July 2004). "Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients?". Am. J. Surg. Pathol. 28 (7): 946–52. PMID 15223967.

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