CHAPTER 18: MALE GENITAL SYSTEM

Penis
• Malformations
o Most common include abnormalities in location of distal urethral orifice  hypospadias and
epispadias
 Hypospadias is the more common of the two; designates an abnormal opening of the urethra
along the ventral aspect of the penis; urethral orifice is sometimes constricted causing urinary
obstruction and increased risk of UTI
 Epispadias indicates presence of urethral orifice on dorsal aspect of penis; produce lower
urinary tract obstruction resulting in incontinence; commonly associated w/ bladder extrophy
• Inflammatory Lesions
o Primarily caused be STDs
o Balanitis and balanoposthitis  refers to local inflammation of glans penis or the glans penis and
overlying prepuce, respectively
o Phimosis  represents a condition in which prepuce cannot be retracted easily over glans penis
o Paraphimosis  when stenotic prepuce is forcibly retracted over glans penis, circulation to glans
may be comprised w/ resultant congest/swelling/pain of distal penis
o Genital candidiasis  fungi loves warm, moist conditions; particularly common in diabetics
• Neoplasms
o Most originate from squamous epithelium
o Uncommon in the US, but common in developing countries
o Uncircumcised, poor hygiene, smoking, and infection w/ HPV 16 and 18 predisposes pathogenesis
o Appearance of intraepithelial neoplasia (carcinoma in situ)  squamous cell carcinomas 
invasive squamous cell carcinoma
o Carcinoma in situ occurs in three forms:
 Bowen disease
• Occurs in older men
 Bowenoid papulosis
• Histological identical to Bowen’s disease, but presents w/ multiple reddish brown
papules on penis; occurs in young sexually active men
 Erythematosus plaque-like lesion on shaft of penis – erythroplsia of Queyrat
• This can also occur elsewhere eon the skin/mucosa, not just on the penis
o Squamous cell carcinoma
 Appears as grey, crusted, popular lesion, most commonly on glans penis or prepuce
 Most cases occur in uncircumcised males who are smokers
 Verrucous carcinoma  variant of squamous cell carcinoma

Scrotum, Testis, and Epididymis

• Hydrocele  most common cause of scrotal enlargement; an accumulation of serous fluid w/in tunica
vaginalis
• Hematoceles  accumulations of blood
• Chyloceles  accumulations of lymph
• Elephantiasis  lymphatic obstruction caused by filariasis
• Cryptorchidism and Testicular Atrophy
o Cryptorchidism  failure of testicular descent into scrotum (usually descended during last 2 months
of intrauterine life)

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  Diagnosis difficult before one year of age
 A common feature in congenital disorders (i.e. patients w/ Pradi-Willi syndrome)
 Bilateral  sterility
 Unilateral  may be associated w/ atrophy of contralateral descended gonad, leading into
sterility
 Failure to descent I s also associated with increased risk of testicular malignancy, 3 to 5-
fold!!!
• Orchipexy before puberty decreases the likelihood of atrophy and reduces (not
eliminate) the risk of cancer and infertility
• Inflammatory Lesions
o Inflammatory lesions of testis are more common in epididymis than in testis proper
o Nonspecific epididymititis and orchitis
 Usually begin primary UTI w/ secondary ascending infection of testis via vas deferens or
lymphatics of spermatic cord
 Involved testis is typically swollen and tender
 Orchitis complicates mumps infection in some adult males but rarely in children
o Infections/autoimmune injury may elicit a granulomatous inflammatory reaction in the testis
 i.e. tuberculosis, which is the most common
• generally begins as epididymitits w/ secondary involvement of testis
• Testicular Neoplasms
o Testicular neoplasms are the most important cause of firm, painless enlargement of the testis
o In adults, 95% of testicular tumors arise from germ cells, and all are malignant
o Neoplasms derived from Sertoli or Leydig cells are uncommon, and are benign
o Recall: Cryptorchidism is associated w/ a 3 to 5 fold increase in the risk of cancer in undescended
testis
o Intersex syndromes (androgen insensitivity syndrome, gonadal dysgenesis) are also associated w/
increased risk
o Most common cytogenetic abnormalities is an isochromosome of the short arm of chromosome 12
o Testicular tumors are more common in whites than in blacks
o Classification and Histogenesis
 Primitive cells  seminomas OR nonseminomatous germ cell tumors (totipotent)
• Seminomas
o Often remain confined to the testis and spread mainly to para-aortic nodes,
rarely to distance sites
• Nonseminomatous
o Tends to metastasize early via blood and lymphatics
o Nonseminomatous cells  embryonal carcinomas  yolk sac tumors and
chroiocarcinomas or teratomas
o Clinical Features
 Stages:
• I: confined to testis
• II: regional lymph node metastases only
• III: nonregional lymph node and/or distant organ metastasis
 Tumor markers
• hCG  produced by cyncytiotropholbastic cells; always elevated in patients w/
choriosarcinoma and seminoma
• AFP  normally synthesized by fetal yolk sac; nonseminomatous germ cell tumors
contain elements of yolk sac
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 o Therefore, presence of AFP is a reliable indicator of presence of
nonseminomatous tumor
 Treatment: chemotherapy; Lance Armstrong won the Tour de France 7x after being treated!

Prostate
• Prostatitis
o Acute bacterial prostates  same organisms that cause acute UTI – E. coli and other gram negs
o Chronic prostates  can be bacterial or abacterial
 Bacterial  bacteria similar to the ones that cause acute can be isolated
 Abacterial  all bacteriologic findings are negative (i.e. Chlamydia trachomatis and
Ureaplasma urealyticum)
o Clinical Features
 Manifestations include dysuria, urinary frequency, lower back pain, and poorly localized
suprapubic or pelvic pain
 Chronic prostatiis even if asymptomatic, serves as a reservoir for organisms capable of
causing UTIs – in other words, it’s a major cause of UTIs in men
• Nodular Hyperplasia of the Prostate
o Prostatic parenchyma: peripheral, central, transitional, and periurethral zones
 Hyperplastic lesions  inner transitional and central zones
 Carcinomas  peripheral zones
o Nodular hyperplasia aka glandular and stromal hyperplasia
 Extremely common abnormality of prostate
 Androgens have a central role in its development
 Does not occur in men that are castrated before onset of puberty or in men w/ genetic
diseases that block androgen activity
• DHT (from testosterone via 5α -reductase and 3α -androstanediol) is the major
stimuli for stromal and glandular proliferation
 Common manifestations are those of lower urinary tract obstruction
• Carcinoma of the Prostate
o Most common visceral cancer in older males, between 65-75 yo
o Prostate cancer does not develop in males castrated before puberty, indicating that androgens
probably contribute to its development
o Arise most commonly in the outer, peripheral glands and may be palpable by rectal exam
o Hereditary
 More common and occurs at earlier age in American blacks than whites, Asians, Hispanics
 Familial  chromosome 1 susceptibility
 Sporadic  hypermethylation of glutathione S-transferase p1 (GSTP1) on chromosome 11
o Frequency of incidental prostatic cancers is comparable in all races
o Environmental influences
 Common in Scandinavian countries
 Uncommon in Japan and other Asian countries
o The presence of osteoblastic metastases in an older male is strongly suggestive of advanced
prostatic carcinoma
o Prostate-specific antigen (PSA)
 Usually secreted in high concentrations into prostatic acini and then into seminal fluid, where
it increases sperm motility by maintaining seminal secretions in liquid state
 Normal upper limit at PSA is 4.0 ng/L
• Cancer cells produce more than that
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 • <4.0 ng/mL are normal
• >10ng/mL  prostatic cancer

Sexually Transmitted Diseases

• Chlamydia, gonorrhea, AIDS, syphilis, and HBV requires notification to CDC
• Two most common STD in US is genital herpes and genital HPV infection, both of which do not require
notification
• Syphilis
o Aka lues, is a chronic venereal infection caused by spirochete Treponema pallidum
o African Americans affected 30x more than whites
o Summary:
 Development of chancre
 Systemic dissemination of organisms continues during this period while host mounts an
immune response
• Nontreonemal Ab
• Treponemal Ab
 Chancre resolves w/in 4-6 weeks
 Manifestations include generalized lymphadenopathy and variable mucocutaneous lesion
 Mucocutaneous lesion of both primary and secondary syphilis are teeming with spirochetes
and are highly infectious
o Primary Syphilis
 Characterized by presence of “hard” chancre at site of initial inoculation (“soft chancre” is
caused by Haemophilus ducreyi)
 In males  primary chancre on penis; females  multiple chancres may be present, usually
in vagina or on uterine cervix
 Serologic tests for syphilis are often negative during early stages of primary syphilis
o Secondary Syphilis
 ~2 months of resolution
 Manifestations: combo of generalized lymph node enlargement and a variety of
mucocutaneous lesions
 Involvement of palms of hands and soles of feet is common
 Condylomata lata  lesions occur in moist skin areas – anogenital region, inner thighs, and
axillae
 Histology of secondary syphilis  characteristic proliferative endarteritis accompanied by
lymphoplasmacystic inflammatory infiltrate
 Both nontreponemal and antitreponemal Ab tests are strongly positive in virtually all cases
of secondary syphilis
o Tertiary Syphilis
 Develops after a latent period of 5 years or more
 Three major categories:
• Cardiovascular syphilis
o 80% of cases
o Usually in forms of syphilitic aortitis
o More common in men than women
o Characterized by slowly progressive dilation or aortic root and arch w/
resultant aortic insufficiency and aneurysms of proximal aorta
• Neurosyphilis
o 10% of cases
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 o variants include chronic meningovascular disease, tabes dorsalis, and a
generalized brain parenchymal disease (general paresis)
• Benign tertiary syphilis
o Uncommon
o Gummas occur mostly commonly in bone, skin and mucous membranes of
upper airway and mouth, but any organ can be affected
o Spirochetes are rarely demonstrable with the lesions
 All forms occur singly or in combo
 Nontreponemal Ab tests may revert to negative during the tertiary phase although
atnitreponemal Ab tests remain positive
o Congenital Syphilis
 Transmission: via placenta during any time of pregnancy; greatest during primary and
secondary stages of the disease when spirochetes are most numerous
 Stigmata of congenital syphilis typically do not develop until after the 4th month of pregnancy
• w/ no treatment, 40% die in utero
 Manifestations: stillbirth, infantile syphilis, and late9tardive) congenital syphilis
• Among those that are stillborn, manifestations are hepatomegaly, bone abnormalities,
pancreatic fibrosis, and pneumonitis
• Infantile syphilis refers to congenital syphilis in live-born infants
o Affected infants present w/ chronic rhinitis (snuffles) and mucocutaneous
lesion
o Visceral and skeletal changes resembling those seen in stillborn infant may
also be present
• Late, or tardive congenital syphilis
o Refers to cases of untreated syphilis of more than 2 yrs duration
o Manifestations include the Hutchinson triad  notched central incisors,
interstitial keratitis w/ blindness, and deafness from 8th cranial nerve injury
o Other changes include saber shin deformity, deformed molar teeth (“mulberry
molars”), chronic meningitis, chorioretinitis, and gummas of the nasal bone
(“saddle-nose” deformity)
 Placenta is usually enlarged, pale, and edematous
o Serologic Tests for Syphilis
 PCR-based testing has been developed, but serology remains the mainstay of diagnosis
 Nontreponemal tests measure Ab to cardiolipin, an Ag that is present in both host tissues and
the treponemal cell wall
• Ab are detected by rapid plasma regain (RPR) and Venereal Disease Research
Laboratory (VDRL) tests
• Ab test begin to become + after 1-2 weeks post infection and are usually + by 4-6
weeks
• They may be negative in the late latent or tertiary phases of disease
• Nontreponemal Ab tests are often negative during earl stages of disease
o Even in the presence of a primary chancre
o So the only way to confirm diagnosis is to do direct visualization of
spirochetes by dark-field or immunofluorescence
• As many as 15% of + VDRL tests represent biologic false+ results
 Treponemal Ab tests
• Include fluorescent treponemal Ab absorption test and the microhemagglutination
assay for T. pallidum Ab
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 • Test becomes + w/in 4-6 weeks (same as nontreponemal), but remain + indefinitely
(unlike nontreponemal)
o So.. not a good screening test
• Serologic test may be delayed, exaggerated, or absent in patients w/ syphilis and
coexistent HIV infection
• Gonorrhea
o STD of lower genitourinary tract caused by Neiserria gonnorrhoeae
 Can become disseminated in individuals w/ deficiency of complement
o Most common reportable communicable disease in US
o N. gonorrhoeae is a fastidious organism and spread of infection requires direct contact w/ mucosa
(no evidence of contracting this from toilet seats or fomites)
o Bacteria initially attach to epithelium (usually columnar or transitional) using their pili; they then
penetrate through epithelial cells and start doing their thing
o In most infected males, gonorrhea is manifested by the presence of dysuria, urinary frequency, and
a mucopurulent urethral exudate w/in 2-7 days of infection
 Untreated infections may ascend to involve the prostate, seminal vesicles, epididymis, and
testis; cause urethral stricture; worst cases, sterility; (above all, they’re become CHRONIC
CARRIERS!)
o Females, initial infection may be asymptomatic or associated w/ dysuria, lower pelvic pain, and
vaginal discharge
 Untreated, may lead to salpingitis and inflammation of the ovaries
 Chronic scarring of fallopian tubes can occur resulting in infertility and an increased risk of
ectopic pregnancy
 Infection can spread to the peritoneal cavity where exudate may affect the liver 
gonococcal perihepatitis
o More commonly in homosexuals, sites of primary infection include oropharynx and anorectal area
w/ resultant acute pharyngitis and proctitis
o Disseminated infection is not common; but more common in females than males
o Gonococcal infection may be transmitted to infants during passage through canal
 Babies develops purulent infection of eyes (ophthalmia neonatorum), an important cause of
blindness in the past
o Diagnosis can be made by culture of the exudates as well as by nucleic acid amplification techniques
• Nongonococcal Urethritis and Cervicitis
o NGU and cervicitis are the most common forms of STDS today
o Organisms include:
 C. trachomatis, T. vaginalis, U. urealyticum, and M. genitalium
 Most cases are apparently caused by C. trachomatis, and this organism is believed to be the
most common bacterial cause of STD in the US.
 U. urealyticum is the next most common cause of NGU
o C. trachomatis
 Gram neg bacterium that is an obligate intracellular parasite
 Two forms:
• Elementary body – capable of at least limited survival in extracellular environment;
taken up by cell via receptor-mediated Endocytosis
• Reticulate body – once inside the cell, elementary body differentiates into its
metabolically active form
 Using energy sources fro host, the reticulate body replicates to form new elementary bodies
 Preferentially affects columnar epithelial cells
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 May be associated w/ clinical features that are indistinguishable from those caused by N.
gonorrhoeae
• Patients develop epididymitits, prostatitis, pelvic hepatic inflammation, and those that
have fun with anal intercourse, proctitis
 Primary infection is characterized by mucopurulent discharge containing a predominance of
neutrophils
 In labs, need special media to grow this; so the best diagnosis is made by nucleic
amplification tests on voided urine
 In patients who are HLA-B27 positive, C. trachomatis infection can cause reactive arthritis
along w/ conjunctivitis, and generalized mucocutaneous lesions  Reiter syndrome
• Lymphogranuloma Venereum
o LGV is a chronic, ulcerative disease caused by strains of C. trachomatis, which are distinct from
those causing the more common NGU/cervicitis
o In US and Western Europe, sporadic
o In Asia, Africa, Caribbean, South America, endemic
o LGV is associated with sexual promiscuity (what does that even mean?! =P)

• Chancroid (Soft Chancre)

o Sometimes called the “third” venereal disease (after syphilis and gonorrhea)
o Is an acute, ulcerative infection caused by Haemophilus ducreyi
o Most common in tropical and subtropic areas and more prevalent in lower socioeconomic groups
 In the book it suggests that lower SES groups have more encounters w/ prostitutes
o Chancroid is one of the most common causes of genital ulcers in Africa and southeast Asia
 An important cofactor in HIV-1 transmission
o Speculation: probably underdiagnosed in US cause most STD clinics don’t have the right things to
isolate H. ducreyi and PCR-based tests are not widely available
• Granuloma Inguinale
o Caused by Calymmatobacterium granulomatis (related to my fav bacteria Klebsiella)
o Uncommon in US and Western Europe but endemic in tropic regions
o In urban settings, transmission of C. granulomatis is typically associated w/ sexual promiscuity
o Untreated  extensive scarring, often associated w/ lymphatic obstruction and lymphedema of
external genitalia
o Culture of the organism is difficult and PCR-based assays are not widely available
• Trichomoniasis
o T. vaginalis is a protozoan that is a frequent cause of vaginitis
o In females  T. vaginialis infection is associated w/ loss of acid-producing Doderlien bacilli
 May be asymptomatic, but frequently causes itching and a profuse, frothy, yellow vaginal
discharge
o In males  asymptomatic
• Genital Herpes Simplex
o Common STD in US
o HSV-1 and HSV-2 can cause genital or oral infections, but most genital herpes are caused by HSV-2
o Transmission requires direct contact because virus is readily inactivated at room temperature or
particularly if dried
o Herpes genitiis is generally not life-threatening
o It is a threat to immunosuppressed patients
 Neonatal herpes infection – acquired during passage through canal

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 • Manifestations: rash, encephalitis, pneumonitis, hepatic necrosis
• 60% die
• Human Papillomavirus Infection
o HPV is the cause of a number of squamous proliferations in the genital tract including condylomata
acuminata, precancerous lesion, and other carcinomas
o Condylomata acuminata
 Aka venereal wars
 Caused by HPV 6 and 11
 Occur on the penis and on female genitalia
• DON’T confuse this w/ the condylomata lata seen in secondary syphilis