prostate

Pathology

 prostatic pathology / prostate pathology

Synopsis

 Function: conduit for urine, adds nutritional secretions to sperm to form semen during ejaculation
 20 g, funnel shaped, 4 x 3 x 2 cm
 Within true pelvis between bladder neck (base of prostate) and urogenital diaphragm / levator ani muscle (apex of prostate)
 Apex contains some muscle fibers from urogenital diaphragm
 Seminal vesicles extend from posterior prostate to posterior surface of bladder
 Ampulla of Vas (ductus) deferens and terminal seminal vesicle duct form ejaculatory duct, join prostatic utricle to open into prostatic urethra
 Denonvillier’s fascia (aka rectovesicle septum): thin layer of connective tissue that separates prostate and seminal vesicles from rectum
 Prostatic urethra begins on superior surface, descends almost vertically, with continuous prostatic utricle extending to posterior prostatic wall, exits anteriorly; divided into halves by sharp 35 degree angle midway, at site of verumontanum (bulge along posterior proximal urethra; site of emptying of ejaculatory, central and transition zone ducts)
 Peripheral zone ducts empty into distal urethra
 Prostatic nervous plexus supplies prostate, seminal vesicles, corpus spongiosum, corpora cavernosum and urethra; nerves distributed evenly in apex, mid gland and base of prostate, AJCP 2001;115:39

Anatomical models

 Embryologic model: 5 lobes: 2 lateral plus posterior, middle, anterior lobes
 Other model (not used): 2 lateral lobes, small median lobe (contains posterior lobe, forms floor of urethra)
 Current model (McNeal): transitional, central, peripheral, periurethral zones
 McNeal zones
 Outer (cortical) zones are termed “peripheral” and “central”; central is towards base
 Inner (periurethral) zone is termed “transitional”

Histology

 Transition zone

• 5% of prostatic volume; 2 pear shaped lobes surrounding proximal urethra
• Site of nodular prostatic hyperplasia, may expand to bulk of gland
• Site of 10% of prostate cancers (large duct carcinomas)
• 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 cancers
• Unlike peripheral and transition zones, ducts are large and irregular; glands are complex with tall columnar, pseudostratified, papillary infoldings; striking basal cell layer with eosinophilic cytoplasm
• Stroma is densest in central zone, least dense in peripheral zone, in between for transition zone (Hum Path 2002;33:518)

 Peripheral zone

• 70% of prostatic volume, from apex posterior to base, surrounds transition and central zones
• Site of 80% of prostate cancers
• Has loose fibromuscular stroma with widely spaced smooth muscle bundles, moderate gland complexity

 Prostatic non-glandular tissue

• “Capsule”: fibromuscular layer most prominent along base and posterior portion of lateral borders; an inseparable component of prostatic stroma, not a distinct capsule, (AJSP 1989;13:21)
• Along lateral borders, fibrous septa traverse periprostatic fat and merges with fibromuscular stroma
• Anteriorly, prostatic stroma merges with fibromuscular tissue of urogenital diaphragm
• Stroma contains abundant smooth muscle, which duplicates function of myoepithelial cells in breast; i.e. squeezes out secretions

 Prostatic glandular tissue

• Prostate glands found normally within skeletal muscle at apex, anteriorly, and in distal posterolateral gland
• Secrete normal mucins, produce pigment (lipofuscin), are androgen sensitive (castration causes atrophy); differentiation and growth is androgen dependent
• Large prostatic ducts have single layer of urothelial-like epithelium without umbrella cells, which is PSA/PAP positive; may undergo squamous metaplasia with estrogen therapy
• Benign tissue may contain hyaline globules (degenerative, aka thanatosomes, AJSP 2003;27:700), may be adjacent to skeletal muscle or nerves

Type of cells

secretory cells, basal cells, scattered neuroendocrine cells, urothelium, ejaculatory duct/seminal vesicle type cells

 Secretory cells

• Located along glandular lumen
• Positive stains: prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), vimentin, keratin (some), Leu7/CD57, EMA (80%), CEA (25%)
• Negative stains: CK903 (34 beta E12, high molecular weight keratin)

 Basal cells

• Separate secretory cells from basement membrane; consist of low cuboidal epithelium and columnar mucus secreting cells; may have prominent nuclear groove, prominent nucleoli
• May be reserve cells (stem cells), can undergo myoepithelial metaplasia but are NOT myoepithelial cells
• Their presence differentiates benign conditions (basal cells are present) from well differentiated adenocarcinoma (not present)
• Positive stains: CK903 (34 beta E12 / high molecular weight keratin), p63, androgen receptors
• Negative stains: PSA, PAP, S100, actin

 Neuroendocrine cells

• Irregularly distributed
• Positive stains: chromogranin A, B, secretogranin II, peptide hormones, PSA
• Negatives stains: androgen receptors

 Urothelium

• In proximal 2 mm of prostatic ducts

 Ejaculatory ducts and seminal vesicles

• Lined by double cell layer of pseudostratified epithelium, contain lipofuscin (golden-brown pigment), have large, hyperchromatic nuclei (also called "monster" nuclei), may have intranuclear inclusions

 Mucins

• Normal mucins are neutral; most adenocarcinomas secrete acidic and neutral mucins

 Glandular secretions

• Can identify with glutaraldehyde based fixatives, fill the normal secretory cell cytoplasm, distinct bright red on H&E staining because of high polyamine content; also present in penile urethra, (Hum Path 2002;33:905)