• Disorders of the
include:
• a
,
and
and
and

• Abnormal opening of the urethra onto the ventral surface of the penis or scrotum.
• This results from failure of fusion of the urethral folds, i.e., it is a form of feminization. Occurs 1 in
250 male alive births.
• There is often associated cryptorchidism, ureterovesical reflux, inguinal hernia, and/or other developmental problems.
• Right now there is a pop claim that hypospadias has doubled in frequency in the past twenty years, and the cause is chemical pollutants acting as "endocrine disruptors".

• The urethral meatus may open on the ventral surface of the penis, at the base of the penis or the perineum.
• This infant with ambiguous genitalia was a genetic male. The arrow points to the urethral orifice that opens unto the perineum.

PHIMOSIS
• Present when the preapuce can not be retracted over the corona.
• Phimosis may be congenital, the orifice of the prepuce being too small.
– More often, phimosis is due to poor hygiene, resulting in chronic inflammation and scarring, which sets up a vicious cycle requiring circumcision.
• Such an ongoing infection of the glans and prepuce is called balanoposthitis .
• Paraphimosis results when a tight foreskin is forcibly retracted, and edema of the glans prevents its replacement.
This can quickly lead to acute urinary retention and even gangrene of the glans.

• Abnormal opening of the urethra on the dorsal surface of the penis.
• Epispadias is a form of extrophy of the urinary bladder.
• There is usually an associated separation of the pubic bones and inadequacy of the urinary sphincters.
• Incontinence and bladder infections are usual.
• Epispadias is fortunately less common than hypospadias and more difficult to correct surgically.

• A persistent, non-pleasurable erection.
• "Priapus" was the classical-era Greek god of erections.
• Most cases of priapism are probably due to obstruction of the deep dorsal vein of the penis.
• Causes:
• idiopathic
• sickle cell disease
• leukemia
• metastatic cancer
• papaverine treatment of impotence (rare)
• trauma.

• Fournier’s gangrene
• Necrotizing fasciitis of genitalia and perineum
• Usually due to Staph or Strep in children; gram negative rods or anaerobic bacteria in adults
• Affects Buck’s fascia and foreskin, sparing glans
• Risk factors: trauma, burns, anorectal disease, diabetes, leukemia, alcoholic cirrhosis

• Due to chlamydia, mycoplasma, trichomonas, perhaps others,
• Important sexually-transmitted diseases.
• Gonorrhea tends to come on fast after the contact, while chlamydia comes on insidiously.
• Gonorrhea tends to have a more purulent discharge.

The triad of
• (1) arthritis involving many joints,
• (2) conjunctivitis, and
• (3) urethritis.
• It is a male’s disease and lasts for several months.
• The urethritis is usually (if not always) chlamydia, and one new study finds chlamydial RNA in the synovium; if the initial episode of urethritis is treated appropriately,
• As with other "reactive arthropathies", there's an impressive proliferation of T-cells specific for chlamydia within the affected joints.
• Patients with Reiter's syndrome are likely to have circinate balanitis, keratoderma blennorrhagica of soles, ulcers of the mouth, iritis, or even ankylosing spondylitis.

• Proliferation of dense fibrous tissue involving a portion of the fascia.
• This leads to curvature of erection.
• Other names:
– "painful erection in the wrong direction",
– "squint of the cock".
• This is one of several abnormal hyperplasias of fibrous tissue which are sometimes called "fibromatoses “ .
– Another common one is palmar fibromatosis (Dupuytren's contracture of the hand) which often occurs with Peyronie's disease.
• Metaplastic ossification and calcification are common.
• Treatment for Peyronie's disease is not very satisfactory, and many patients eventually require a penile prosthesis.

Female causes 50%
Male causes 50%
• Pretesticular
• Testicular
• Post testicular

Focal testicular atrophy

Testicular atrophy

– Spermatogenesis can be temporarily diminished or even stopped by a host of factors ranging from heavy drinking to anabolic steroid abuse to alcoholism to bicycling.
– Obstruction of the sperm passages may be more amenable than the above to surgical help.

CRYPTORCHIDISM (cryptorchism)
– Incomplete descent of the testis into the scrotal sac.
– Unilateral or bilateral cryptorchidism occurs in around 4% of prepubertal boys.
– Cryptorchid testes may be found anywhere along the normal route of descent (abdomen, inguinal canal, prepubic).
– The epididymis is likely to be malformed or at least elongated.
– Ectopic testis is less common; it may stray into the superficial inguinal region, penis, or femoral sheath.

– Failure of the testes to descend into the scrotum causes problems:
• The tubules will undergo atrophy and fibrosis, beginning in infancy and advanced around puberty.
• There is an increased risk of torsion of the spermatic cord and gangrene of the testis.
• The risk of germ cell cancer (usually seminoma) in undescended testes is around 30x greater than normal.
– Most cryptorchidism is idiopathic.
– It may be accompanied by
• other developmental abnormalities,
• diethyl-stilbestrol exposure,
• poorly-understood anatomic and hormonal problems.

EPIDIDYMITIS and ORCHITIS
• Non-specific infections of the contents of the scrotum are usually complications of urinary tract infection, instrumentation or prostate surgery.
• Gonorrhea : the infection often spreads to the epididymis, less often the testis.
• Mumps : orchitis is common in adolescents and adults. It usually follows the onset of parotitis by a week or so, and may cause atrophy of the germinal epithelium and infertility. The Leydig cells are spared.
• Tuberculosis : granulomas involving the epididymis; may spread to the testis.
• Syphilis : gummas involving the testis; may spread to the epididymis.

TORSION OF SPERMATIC CORD
("torsion of the testis")
– Twisting of the spermatic cord is likely to result in venous infarction and gangrene in a few hours.
– This is quite common, especially in children and adolescents.
– The involved testis is painful and elevated; the cord is typically twisted.
– There may or may not be a history of trauma
(often minor, as in baseball or break dancing.
– The underlying problem may be abnormal fixation of the testis or cryptorchidism.

• Fluid in the tunica vaginalis.
• Usually idiopathic
• A hydrocele may contain 100 cc or more of serous fluid.
• If ascites is present and the patient has a patent processus vaginalis, a hydrocele will appear and disappear as the patient changes position.
• One can distinguish a hydrocele from a tumor mass by trans-illuminating it with a bright flashlight in a dark room.

• Hematocele
• Blood in the tunica vaginalis.
• May follow trauma, or a sing of an underlying testicular cancer.
• Chylocele
• Accumulation of lymphatic fluid in the tunica.
• Spermatocele
• A cystic lesion up to 1 cm or so in the area of the rete testis, filled with fluid and dead sperms.
• Varicosities of the pampiniform plexus,
• Usually on the left side.
• This is common in young men, may cause fertility problems by warming the testes.
• A new varicocele in an old man often indicates occlusion of the vein by renal cell carcinoma.

• Acute and chronic prostatitis are uncomfortable problems, and are common in
– sexually-transmitted urethritis
– lower urinary tract infections.
• E. coli is the most common etiologic agent of both acute and chronic prostatitis.
• The diagnosis depends on physical and lab exams.
• In acute prostatitis the gland is exquisitely tender.
• Gonorrhea is an important cause of acute prostatitis
(secondary to urethritis; it can also cause epididymitis).
• In chronic prostatitis the gland is somewhat tender and the prostatic fluid contains WBC's and bacteria.

• Granulomatous prostatitis may be due to
– Tbc (hematogenous spread from the lungs),
– "idiopathic" (no Tbc, no caseation, no clues as to the etiology).
– The histiocytes may resemble cancer cells.
• In " non-bacterial prostatitis ", the findings are as in chronic prostatitis, but no organisms grow, probably;
– Chlamydia
– Trichomonas
– Autoimmunity
– Heroic abstinence.

• is a stress-related pain syndrome in which there are no WBC's in the prostatic fluid.
• Other exacerbating factors include
– constipation,
– smoking,
– coffee,
– spices .

• Benign prostatic hypertrophy or hyperplasia, BPH.
• Most men over about age 50; 10% of men living to age 80 will need prostate surgery.
• The normal prostate weighs around 20 gm. Old men's prostates enlarge to 60-200+ gm.
• The increased tissue is nodular overgrowth of periurethral glands and stroma.
• Press upon the prostatic urethra.
• The hyperplasia most often involves the lateral and median lobes.
• Median lobe hyperplasia by itself produces a
"median bar", obstruction without an enlarged gland.

• The etiology of prostatic hyperplasia is obscure.
– Hormonal imbalance with ageing.
– Estrogen sensitive peri-urethral glands.
– Accumulation of dihydrotestosterone in the prostate and its growth-promoting androgenic effect.
• Heroin abuse is also rumored to be a risk factor.
• The most interesting work right now focuses in a nerve-growth factor-like protein produced by the stromal cells which causes hyperplasia of both glands and stroma

• Microscopy
– Nodular prostatic hyperplasia consists of nodules of glands and intervening stroma
(mostly glands)
– The glands variably sized, with larger glands have more prominent papillary infoldings.

Prostatism (This is a clinical term)
• frequency (i.e., only small amounts are voided at a time),
• nocturia (urinating at night, same reason),
• difficulty starting and stopping urination,
• incontinence (dribbling),
• dysuria (painful urination),
• hernias (from straining),
• acute urinary retention (emergency)
• hematuria (due to stretching of veins),
• bladder hypertrophy and trabeculation (accentuation of the normal muscles),
• bladder diverticula, bladder stones,
• hydronephrosis,
• renal failure

Condyloma acuminatum
• A papillary, keratinizing lesion caused by the sexuallytransmitted "human papilloma virus" (usually strain 6).
• In males, it commonly occurs in the urethral meatus, which is a mess.
Condyloma latum
• Groups of flat-topped lesions which may ooze serous fluid
• caused by secondary syphilis.
• Typically occur in skin folds.
Pearly penile papules
• Little bumps, sometimes hairy, which pop up in young adults, especially on the corona.
• Each is a single big dermal papilla. No need to treat.

• Erythroplasia of Queyrat
– A raised, velvety plaque on the uncircumcised glans or prepuce.
– Histologic study shows dysplasia of the squamous epithelium.
– A minority of cases (5-10%) develop into squamous cell carcinoma if not removed.
• Bowen's disease
– Carcinoma in situ of the skin, most often on the penis or scrotum in men.
– Some cases (maybe 10%) develop into invasive squamous cell carcinoma.
– In many cases, the appearance of Bowen's disease on the skin heralds the growth of another malignancy internally.
– Bowen's disease tends to spare the sweat glands and involve the hairs.

• Bowenoid papulosis
– Multifocal intraepithelial neoplasia, caused by HPV-16.
– The atypia is mild.
– Bowenoid papulosis tends to spare the hairs and involve the sweat glands.
– Bowen's disease tends to spare the sweat glands and involve the hairs.
• Giant condyloma of Buscké-Lowenstein
– verrucous carcinoma
– HPV-related, cauliflower-like lesion.

• Almost all are variations on squamous cell carcinoma
• This is a disease of older men (~60 years)
• It originates on glans and prepuce.
– Only 1% of cancers among American men begin on the penis; the figure is as high as
18% in the Orient.

• Risk factors :
– phimosis,
– smegma,
– balanoposthitis,
– infection with HPV (notably HPV-16).
• Males circumcised as infants almost never get cancer of the penis. The incidence is much lower in those circumcised at a later age than among the uncircumcised.
• Carcinoma of the penis spreads to the inguinal lymph nodes.
• Five year survival is around 50% overall.

• Scrotal squamous cell carcinoma is the subject of the famous chimney sweep story.
• Many older men get a few angiokeratomas
(hemangiomas with each dermal papilla stretched wide by a single ectatic blood vessel), especially on their scrotums.

• Over 95% of tumors of the testis are malignant germ cell tumors.
• Testicular neoplasms are the most important cause of firm, painless enlargement of the testis.
• Such neoplasms occur in roughly 5 per 100,000 males, with a peak incidence between the ages of 20 and 34 years.
• Current thinking about the histogenesis of cancers of the testis emphasizes their common origin from germ cells:

• All present as painless, non-tender masses in the testis.
• The primary may be occult, especially pure choriocarcinomas.
• Many cause gynecomastia (after puberty) or precocious puberty (children)
• Risk factors
– cryptorchidism
– some intersex malformations
– familial.

• Seminoma
• Embryonal carcinoma
• Choriocarcinoma
• Yolk sac tumor (endodermal sinus tumor)
• Teratoma &Teratocarcinoma

• Cancer that closely resembles young spermatocytes.
• Grossly these tumors are homogeneously soft and yellowish.
• Tumor cells have "fried egg" appearance (glycogen-rich cytoplasm); arranged in masses separated by fibrous septa with a lymphocytic infiltrate, may have syncytiotrophoblast and/or granuloma formation.
– Variant: spermatocytic seminoma of older men has somewhat different histology, no in situ phase, even better prognosis (it almost never metastasizes).

• Chorionic gonadotropin ( hCG ) is a tumor marker for the
50% or so of seminomas that contain syncytiotrophoblast
(i.e., the man has a positive pregnancy test).
• Seminomas typically metastasize to the retroperitoneal lymph nodes and then to the lungs.
• Seminomas are remarkable for their good response to radiation or chemotherapy as appropriate, and even widespread disease can usually be treated with five-year survivals of 95% or better.
• Tumors with histology and response to therapy like testicular seminomas (or other germ cell tumors) also arise in other midline structures including the retroperitoneum, thymus, and pineal ("germinomas"), as well as in the ovary
("dysgerminoma").

Lobules of neoplasitic cells have an intervening stroma with characteristic lymphoid infiltrates. The seminoma cells are large with vesicular nuclei, and pale watery cytoplasm.

Embryonal carcinoma
• A very primitive cancer that arises in the testis.
• Grossly these are grayish-white masses with hemorrhage and necrosis.
• Tumors with an embryonal cell carcinoma component metastasize to the retroperitoneum and everywhere else.
• The cured metastases may turn into scar tissue, or just plain necrotic debris.
• Microscopically, the tumor cells grow in sheets, knobs, etc.
– Distinguish from a seminoma by absent glycogen and positive staining for cytokeratin (seminomas are usually weak or negative).
• Many embryonal cell carcinomas also contain differentiated structures of a teratoma.
– Teratoma + embryonal cell carcinoma = teratocarcinoma.

• embryonal carcinoma mixed with teratoma in which islands of bluish white cartilage from the teratoma component are more prominent.

Choriocarcinoma
• The bloodiest tumor in pathology; solid areas may be hard to find.
• The malignant cells resemble placenta, and the pathologist must identify cytotrophoblast and syncytiotrophoblast.
• There are no villi.
• HCG levels are always very elevated (serum, urine.)
• Choriocarcinoma most often is a component in a teratocarcinoma, but may be pure or mixed with any other germ cell tumor components.
• Until recently, choriocarcinoma arising in the testis was always lethal.
– Today the prognosis is not much worse than for embryonal cell carcinoma, even if the tumor is "pure choriocarcinoma".

Yolk sac tumor (endodermal sinus tumor, orchioblastoma, infantile embryonal cell carcinoma):
• Rare
• The most common testicular tumor of children.
• It is composed of papillary structures (Schiller-Duval bodies) with extracellular globs of alfa-fetoprotein and alfa-1-protease inhibitor.
• Those PAS positive extracellular hyaline globoid material is found typically in yolc sac tumor.
• This carcinoma is also unusual because it metastasizes hematogenously.

• Schiller-Duval body consisting of tumor cells arranged around a blood vessel.
• This structural arrangement is similar to that seen in the developmental stages of the yolk sac.

Hyaline globules of varying sizes are present in endodermal sinus tumors.
These globules may be mistaken for red blood cells but they vary in size and have a differing tinctorial quality than red blood cells. These globules are accumulations of alpha-1-antitrypsin .

• Cystic teratoma of testis is rare (but common in ovary) and seldom contains hair.
• Teratomas are the only testicular tumors that are often cystic.
• Solid teratomas are of two types:
• Mature solid teratoma is benign, usually occurs in children.
• Immature solid teratoma is malignant, usually contains embryonal cell carcinoma (teratocarcinoma) or sometimes squamous cell carcinoma.
• Even if an adult's teratoma appears altogether benign, there is likely to be nearby intratubular carcinoma in situ.

Teratoma with different areas

– Further, any tumor of germ cell origin may metastasize as another histologic type of germ cell tumor.
– We now know both in-situ and microinvasive testicular cancer.
– Germ-cell tumors (seminomas, embryonal cell tumors, teratocarcinomas, choriocarcinomas, teratomas) can and do arise in the retroperitoneum, and mediastinum.

– Leydig cell tumor
– Sertoli cell tumor (androblastoma).
• Leydig cell tumors >Sertoli cell tumors
• Less than 5% of all testicular tumors
• Benign (90%), malignant (10%)
– The gross and microscopic appearances are typical for endocrine tumors.
– Criteria for malignancy are necrosis, mitotic figures, local invasion, and nuclear pleomorphism.
• May elaborate androgens/androgens & estrogens
• Hormonally active (50%) Macrogenitosomia,
Precocious puberty, Gynecomastia

SUMMARY OF TESTICULAR GERM CELL TUMORS
Tumor
Peak
Age
(yr)
Seminoma 40-50
Embryonal carcinoma
20-30
Morphology
Sheets of uniform polygonal cells with cleared cytoplasm; lymphocytes in the stroma
Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation; most contain some yolk sac and choriocarcinoma cells
Yolk sac tumor
3 Poorly differentiated endothelium-like, cuboidal, or columnar cells
Tumor Markers
10% have elevated hCG
90% have elevated hCG or
AFP or both
90% have elevated AFP
Chorio carcinoma
(pure)
20-30 Cytotrophoblast and syncytiotrophoblast without villus formation
100% have elevated hCG
Teratoma
Mixed tumor
All ages
15-30
Tissues from all three germ-cell layers with varying degrees of differentiation
50% have elevated hCG or
AFP or both
Variable, depending on mixture; commonly teratoma and embryonal carcinoma
90% have elevated hCG and AFP

arises in the testes of older men with some frequency.
is a benign, hard spherical nubbin, usually in the head of the epididymis, derived from mesothelium.

• Prostate cancer is the most common cancer in men (age:50-
80)
– Second cancer after lung carcinoma as a cause for tumorrelated deaths among males.
• Latent prostate cancer: found only at autopsy (incidental prostate cancer)
• Occult prostate cancer might pop up in bone marrow or lymph node prior to becoming symptomatic.
• The tremendous increase in the incidence of prostate cancer during the 1990's (about 30%) reflects the improved screening.
• The total number of people dying of the disease is actually decreasing slightly.

• Over age 50
– Prostate cancer is rare in Oriental folks in Asia,
– more common in Asian-Americans,
– common in U.S. whites,
– most common in U.S. Blacks.
• The majority, but not all, prostate cancers arise in the posterior lobe.
• Microcarcinoma : Some more recent studies suggest that, after a man turns thirty, his percentage chance of having a little histological cancer is about the same as his age (30%).
• This is the reason : Occult prostate cancers are common
"incidental" findings in prostate chips obtained at turp.

• Etiology of prostate cancer:
– Essentially unknown.
– Androgens
• early castration prevents the development of adenocarcinoma (lack of sexual activity)
– Exposure to cadmium (i.e., battery factories)
– Animal fat / meat
– Prostate-cancer-family gene (HPC2 / ELAC2).

– Cancer of the prostate presents as a painless lump in the gland.
– These tumors are easier to feel than to see;
• they are firmer than hyperplastic nodules,
• poorly circumscribed, and yellowish .
– Diagnosis is by biopsy or fine-needle aspiration (first).
– Prostatectomy.
– PSA (prostate-specific antigen)
• urologists are likely to do sextant biopsies on prostates of men with elevated PSA's and no palpable lump.

• The in-situ lesion (prostatic intra-epithelial neoplasia “PIN”) is now well-characterized as well.
– There's always nuclear enlargement and crowding, there are usually nucleoli
– Low-grade "PIN" is common in young men, and it probably takes decades to transform
– Usually these lesions will involve part of a single gland
– Nowadays, the feeling is that PIN requires biopsy.

Grading of PIN
– Low grade loss of secretion, piling up of cells ("tufting"), blue cytoplasm,
– High grade with high Nuclear/Cytoplasmic ratio prominent nucleoli and a papillary or cribriform pattern

TURP-Bits (Diagnosis + Treatment )

• Histology of prostatic adenocarcinoma:
– prominent nucleoli in nuclei with marginated chromatin
– invasion (especially perineural invasion ; at least loss of the normal gland-stroma interaction)
– obvious distortion of the architecture
– loss of the outer layer ("basal layer") of the glands
• (on fine needle biopsy, pathologists pay special attention to the presence or absence of the basal layer)
• As in breast, several benign lesions exist that are easily mistaken for cancer.

Prostate adenocarcinoma Prostate hyperplasia

• Gleason Scoring is used in routine practice.
• There are 5 Gleason patterns regarding to:
Gland formation and degree of differentiation
Grade 1: most well differentiated carcinoma; neoplastic glands are uniform, round, and are packed into well-circumscribed nodules.
Grade 5: Most poorly differentiated carcinoma. No glandular differentiation.
Tumor cells infiltrate the stroma in form of cords, sheets and nests

• The most well differentiated tumors have a
Gleason score of 2(1+1)
• If a carcinoma shows only Gleason pattern 2; the score would be: 4(2+2)
• If it shows a mixed pattern such as some areas
3, some 4; the score would be 7(3+4)
• Gleason score of 10 (5+5) represents the least differentiated carcinoma.

Perineural invasion

• TNM Staging (affects prognosis):
– T1: CLINICALLY INAPPARENT LESION (BY PALPATION/IMAGING
STUDIES)
– T2 : PALPABLE OR VISIBLE CANCER CONFINED TO PROSTATE
– T3: LOCAL EXTRAPROSTATIC EXTENSION
–
T4: INVASION OF CONTIGUOUS ORGANS AND/OR SUPPORTING
STRUCTURES INCLUDING BLADDER NECK, RECTUM,
EXTERNAL SPHINCTER, LEVATOR MUSCLES, OR PELVIC FLOOR
– Uncommon prostate cancers include squamous and endometrioid, plus adenoidcystic, colloid, carcinosarcoma, signet-ring, oat-cell, carcinoid, and lymphoepithelioma.
•
Prostate cancer is often indolent even when it has metastasized, but some prostate cancers are very aggressive.
– Mucin-producing prostate cancer is an aggressive lesion.

– regional lymph nodes
– axial skeleton (causing miserable bone pain often with osteoblastic lesions)
– leptomeninges (not the brain tissue).