Prostate gland & seminal vesicles

• Knowledge of the normal prostate morphology can help with orientation and avoid confusion of these findings with cancer

• Regions (Eur Urol 1991;20:261):
  • Transition zone:
    • 5% of prostatic volume
    • 2 pear shaped lobes surrounding proximal urethra
    • Expands after age 50, causing nodular prostatic hyperplasia; may expand to 95% of gland (Urology 2017;105:136)
    • Site of 10% of prostate cancer
    • Contains moderately compact fascicles of smooth muscle
  • Central zone:
    • 25% of prostatic volume
    • Surrounds transition zone to angle of urethra to bladder base
    • Site of 5% of prostate cancer
    • Unlike peripheral and transition zones, ducts are large and irregular
    • Glands are complex with tall columnar, pseudostratified lining, papillary infoldings and epithelial bridging (can mimic high grade prostatic intraepithelial neoplasia or cribriform cancer)
    • Striking basal cell layer with eosinophilic cytoplasm
    • Stroma is densest in central zone, least dense in peripheral zone, in between for transition zone (Hum Pathol 2002;33:518)
  • Peripheral zone:
    • 70% of prostatic volume, from apex posterior to base, surrounds transition and central zones
    • Site of > 80% of prostate cancer
    • Has loose fibromuscular stroma with widely spaced smooth muscle bundles, moderate gland complexity

Images hosted on other servers:

Contributed by Kenneth A. Iczkowski, M.D. and AFIP

• Secretory cells:
  • Located along glandular lumen
  • Columnar (except if atrophic)
  • Nucleoplasm is dark purple
• Basal cells:
  • Separate secretory cells from basement membrane
  • Consist of low cuboidal epithelium and columnar mucus secreting cells
  • Nucleoplasm is lighter blue and may have prominent nuclear grooves, vacuoles
  • Are reserve cells (stem cells) and can undergo myoepithelial metaplasia but are not myoepithelial cells
  • Undergo hyperplasia causing multilayering and possibly prominent nucleoli in reactive / inflamed prostates
  • Their presence distinguishes benign conditions (basal cells present) from well differentiated adenocarcinoma (basal cells absent), although prostatic intraepithelial neoplasia and intraductal carcinoma retain at least focal basal cells; also, invasive cancer can retain rare basal cells (Am J Surg Pathol 1999;23:147)
• Neuroendocrine cells:
  • Sparse and irregularly distributed population, function is not understood; not perceptible without stains (Precis Clin Med 2021;4:25)
• Immune cells:
  • Modest component of lymphocytes is normal in prostates of all ages, mainly T cells, which are more numerous in the stroma than the epithelium; neutrophils are abnormal and may correlate with clinical prostatitis and raised serum PSA (Prostate 2003;55:187)

Contributed by Kenneth A. Iczkowski, M.D.

Images hosted on other servers:

• Secretory cells: prostatic acid phosphatase (PAP or PSAP), prostate specific antigen (PSA), prostein, NKX3.1 (nuclear), vimentin, keratin (some), Leu7 / CD57, EMA (80%) (Histopathology 2012;60:118)
• Basal cells: cytokeratin 903 (34 beta E12 / high molecular weight keratin), CK5/6, p63, androgen receptor, p40 (Mod Pathol 1999;12:1, Am J Clin Pathol 2009;132:211, Patholog Res Int 2015;2015:897927)
• Neuroendocrine cells: chromogranin A / B, synaptophysin, NSE, CD56 (N-CAM), FOXA2, secretogranin II, peptide hormones, PSA (Precis Clin Med 2021;4:25)

• Secretory cells: cytokeratin 903 (34 beta E12 / high molecular weight keratin), CK5/6, P504S racemase (may be weakly positive), p63, androgen receptor, p40
• Basal cells: PSA, PAP, S100 protein, actin
• Neuroendocrine cells: androgen receptor, cytokeratin 903 (34 beta E12 / high molecular weight keratin) (Precis Clin Med 2021;4:25)

Which of these immunostains marks luminal cells but not basal cells in normal prostate?

1. Androgen receptors
2. CK5/6
3. Cytokeratin 903 (34 beta E12 / high molecular weight keratin)
4. p63
5. PSA

E. PSA will be positive in luminal cells but is not part of the basal phenotype; proliferations and tumors derived from basal cells are also PSA negative. Customary markers used for basal cells include nuclear p63 and cytoplasmic basal cell cytokeratin (34 beta E12) and CK5/6. They also mark with androgen receptors.

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Reference: Prostate gland & seminal vesicles - Anatomy & histology

Thinking about the above image of benign reactive basal cells, what histologic feature is characteristic of a secretory cell but not a basal cell?

1. Acquiring prominent nucleoli
2. Nuclear vacuoles
3. Nuclei may have prominent nuclear grooves
4. Nucleoplasm is darker purple
5. Nucleoplasm is lighter blue

D. Nucleoplasm is darker purple. The secretory cells are less metabolically active than basal cells, giving them a more condensed nucleoplasm. Nuclear vacuoles and grooves, however, are more characteristic of basal cells. Answer A is wrong because basal cells can get somewhat prominent nucleoli if they are reactive; in this case, in response to acute inflammation. However, prominent nucleoli in secretory cells signal PIN or cancer.

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Reference: Prostate gland & seminal vesicles - Anatomy & histology