2. Etiology: DHT is the primary mediator.
a. 5a-Reductase in stromal cells converts circulating testosterone to DHT in the prostate.
b. Estrogen enhances development of BPH by increas- ing the synthesis of androgen receptors for DHT.
3. Gross and microscopic findings (Figure 20-1)
a. Hyperplasia of epithelial and fibromuscular stromal cells leads to the formation of soft, yellow-pink nodules.
b. Nodules develop in the central portion of the pros- tate, causing urethral obstruction.
4. Clinical and laboratory findings
a. Signs of urinary obstruction: difficulty initiating and stopping the urinary stream, dribbling, incom- plete emptying (sense of urgency), nocturia, dysuria b. Hematuria
c. PSA
(1) Proteolytic enzyme that maintains seminal se- cretions in a liquified state
(2) Increased in both BPH and prostate cancer; in BPH, PSA is generally less than 10 ng/mL.
(3) Prostatitis and prostate infarctions also in- crease PSA.
5. Complications
a. Obstruction with urinary retention (most
common): predisposes to hydronephrosis and poten- tial renal failure and sepsis
b. Bladder diverticula, bladder infections, prostate infarction
Most common cause of prostate enlargement in men
> 50 years of age:
BPH
Most common cause of urethral obstruction: BPH
Chapter 20 Lower Urinary Tract and Male Reproductive Disorders 265
Figure 20-2 Prostate cancer.
The arrow points to a
wedge-shaped triangular area of prostate cancer located at the periphery of the gland The central area of the gland shows nodular hyperplasia with nar- rowing of the urethral lumen
D. Prostate cancer 1. Epidemiology
a. More common in blacks than in whites
b. Second most common cause of cancer mortality in men
c. Risk factors: advancing age, history of prostate cancer in father or brother, African-American race, smoking tobacco, diet high in saturated fats 2. Pathogenesis: primarily DHT-dependent cancer that
develops in the peripheral zone; begins as an intraepi- thelial lesion (e.g., prostatic intraepithelial neoplasia) 3. Gross findings: yellow, firm, gritty tumors (Figure 20-2) 4. Microscopic findings: neoplastic glands often invade
contiguous structures (e.g., capsule, nerves).
5. Clinical findings
a. Usually asymptomatic until advanced b. Indurated mass on digital rectal examination
c. Obstructive uropathy, suggesting extension into the base of the bladder
d. Low back and/or pelvic pain, which indicates bony metastases to vertebra and/or pelvic bones; may in- dicate compression of spinal cord
6. Laboratory findings
a. Increased alkaline phosphatase: caused by osteo- blastic metastases
b. Increase in PSA values: highly predictive of cancer c. If screening tests are abnormal, transrectal ultra-
sound with needle biopsies of suspicious sites may be necessary.
7. Clinical course and treatment
a. Prostate cancer spreads via perineural invasion to the capsule. It metastasizes via the lymphatics to the regional lymph nodes and via the blood vessels to the bone (most common), lungs, and liver.
b. The Gleason grading system is based on the degree of differentiation and glandular patterns to grade prostatic tumors.
Most common cancer in men:
prostate cancer
PSA > 10 ng/mL is a strong indicator of prostate cancer
266 Pathology
c. Treatment is radical prostatectomy or radiotherapy.
Hormone therapy blocks the effect of androgens on tumor growth.
V. Male Hypogonadism and Erectile Dysfunction
A. Hypogonadism: decreased production of testosterone or re- sistance to testosterone
1. May result from Klinefelter's syndrome or testicular feminization (see Chapter 5)
2. Clinical presentation: erectile dysfunction (failure to sustain an erection), loss of male secondary sex character- istics, infertility
3. Primary hypogonadism: Leydig cell dysfunction a. Etiology: alcohol abuse, orchitis, radiation
b. Laboratory findings: decreased serum testosterone and increased luteinizing hormone (LH), de-
creased sperm count (testosterone stimulates spermatogenesis)
4. Secondary hypogonadism: hypothalamic or pituitary dysfunction
a. Hypothalamic dysfunction: Kallmann's syndrome (e.g., absent gonadotropin-releasing hormone, inabil- ity to taste and smell)
b. Pituitary dysfunction: hypopituitarism caused by nonfunctioning pituitary adenoma
c. Laboratory findings: decreased LH and decreased testosterone
B. Erectile dysfunction; causes:
1. Psychogenic problems: nighttime erections (nocturnal penile tumescence) still occur.
2. Decreased testosterone (decreased libido)
3. Vascular insufficiency (e.g., Leriche syndrome, or aorto- iliac atherosclerosis)
4. Neurologic disease (autonomic neuropathy in multiple sclerosis or diabetes mellitus)
5. Drugs that block androgen receptors (e.g., alcohol, leu- prolide, methyldopa, psychotropics, spironolactone)
Sildenafil is the most common drug used for the treatment of erectile dysfunction. It inhibits the breakdown of cyclic guanosine monophosphate (cGMP) by type 5 phosphodiesterase. This action increases levels of cGMP, which causes vasodilation in the corpus cavernosum and the penis. Yohimbe (a plant product) also causes vasodilation of vessels.
6. Endocrine disorders (e.g., diabetes mellitus, prolacti- noma)
Most common cause of erectile dysfunction in men
> 50 years of age:
vascular insuffi- ciency
• •
• •
• •
• •
• Female Reproductive
• Disorders and Breast
• • Disorders
• •
•
•
I. Sexually Transmitted Diseases (STDs) and Other Genital Infections
• A. Sexually transmitted diseases
1. Herpes simplex virus type 2 (HSV-2) infections
• a. Recurrent vesicles that ulcerate are located on the vulva, cervix, and perianal area.
b. Tzanck preparation: stained scrapings removed
• from the base of an ulcer show multinucleated
•
squamous cells with eosinophilic intranuclear
inclusions.
• 2. Human papillomavirus (HPV) infections
a. HPV types 6 and 11 are associated with condy-
• loma acuminata (venereal warts); these fern-like
• or flat lesions occur in the genital area (e.g., vulva, cervix, perianal area).
• b. HPV types 16 and 18 are associated with dysplasia and squamous cell carcinoma.
• c. HPV produces koilocytic change in squamous
• epithelium; cells with wrinkled pyknotic nuclei are surrounded by a dear halo (Figure 21-1).
3. Chlamydia: caused by Chlamydia trachomatis, a
• gram-negative intracellular parasite; often coexists with
Neisseria gonorrhoeae Most common STD
• a. Primary infection sites in males and
(1) Males: urethra (nonspecific urethritis), females: chlamydia
• epididymis, anus (proctitis)