Congenital Anomalies of the Penis
- Penile agensis
- Duplication - 2 urethral orifices come out
3 Epispadias - Hypospadias
Penile Epispadias/Hypospadias
- abnormal openings of the urethra on the dorsal or ventral penis from malformations of the urethral canal, can be associated with undescended testes
- Hypospadias is more common (1 in 300 births)
- Clinical: urethral obstruction or failure of normal ejaculatory function
Inflammation of Penis
- most commonly related to phimosis (inability to easily retract foreskin) or venereal disease
- in circumcised/uncircumcised adults, balanoposthitis (glans inflamation = balanitis, foreskin = posthitis) is related to poor hygiene
Circumcision
AAP says there is no absolute medical indication for circumcision
- 60-75% of males in US are circumcised
- decrease in HIV transmission from females to circumcised males of 57%
Penis - Condyloma acuminata
- “warty,” cauliflower like growths which occur primarily in the anogenital region
- venerallly transmitted and most often caused by HPV types 6 or 11
- not premalignat, but tend to recur despite vigorous therapy
- micro: exuberant exophytic (growing outward) growth pattern of the papillary lesion is seen, few mitosis, no necrosis
Penis - Carcinoma in situ
“Bowen disease” - on skin
“erythroplasia or Queyrat” - on glans
-80% related to HPV (type 16)
-10% progress to squamous cell carcinoma if untreated
-red, slightly raised, rough, painless, nonulcerated lesions
Carcinoma in situ: Histology
-hyperkeratosis with disordered maturation and elongation of rete ridges and thickening of epidermis
Penis - Squamous Carcinoma
- related to HPV 50% of the time (type 16 & 18)
- other risk factors: poor hygiene & smoking
Testis - Cryptorchidism
undescended testes (from abdomen to scrotum)
-1% or one year old boys
-75% unilateral/25% bilateral
-may be related to other anomalies (hypospadias)
Transabdominal phase
-mullerian inhibiting substance
-takes testis to brim of pelvis
-failure here in 5-10% of cases
Inguinoscrotal phase
-androgen induced release of calcitonin-gene related peptide
-takes testis from brim of pelvis into sscrotum
-failure here is 90-95% of cases
Cryptochidism Complications
- inguinal testis susceptible to trauma
- Sterility
- decreased spermatogenesis in BOTH testes in unilateral cryptorchidism
- systemic mechanism, poorly understood (not just “overheated testis”)
- orchiopexy before age 2 improves (does not guarantee) chances of normal spermatogenesis
- Neoplasms
- 5-10 fold increase in risk of malignant neoplasm in cryptorchid testis
- some increased risk in contra lateral normally descended testis
- both risks are reduced but not totally eliminated by orchiopexy
Klinefelter Syndrome
- abnormal # or X chromosomes (XXY), primary gonadal insufficiency
- Frequency: 1/1000-4000 live male births; 1/100 patients in mental institutions and 3.4/100 infertile men
Clinical Appearance of Klinefelter Syndrome
- eunuchoid appearance with increased stature and small to normal-sized, well developed testes (firm)
- incomplete virilization
- gyneocomastia
- mental retardation, speech difficulties
-increased incidence of extragonadal germ cell tumors (mediastinum>pineal gland, CNS, retroperitoneum) as well as hypopituitarism
Histology of Klinefelter Syndrome
- small hyalinized seminiferous tubules
- pseudoadenomatous clusters of Leydig cells (appear to increase in number though b/c of decreased testicular volume)
Testis - Mumps orchitis
- focal atrophy of testicular tubules (most common cause)
- post puberty complicated by architis on fourth to third of cases
- unilateral & patchy so that sterility following infection is uncommon
- echovirus, lymphocytic choriomeningitis virus, influenza virus, Coxsckie virus, arboviruses
Epididymitis
- more frequent cause for scrotal pain and swelling in adult males and is most likely to be the result of a sexually transmissible diseases such as chlamydia trachomatis or Neisseria gonorrheae in younger males or gram negative bacteria from urinary tract infection of older males
- disseminated tuberculosis may occassionally involved the epididymis
Testis - Syphilis
Tertiary: involves testis first, then epididymis
-micrograph shows a silver stain of testis with numerous spirochetes
Testis - Gonorrhea
-spreads retrograde from the urethra to the prostate, seminal vesicles, epididymis, and prostate
Testis - Tuberculosis
- spreads retrograde from the prostate to the epididymis, then to the testis
- granuloma
Testis - Granulomatous Orchitis
- uncommon inflammatory testicular lesion that follows a gram negative urinary tract infection in the majority of cases
- most prevalent in 5th/6th decades
- testicular involvement is usually diffuse (may be localized nodular lesion & may simulate neoplasm)
- epididymis & spermatic cord may be involved
Inflammatory Process of Granulamatous Orchitis
- predominately intratubular with the cellular infiltrate containing a majority of histiocytes admixed with lymphocytes and plasma cells
- giant cells
- predominance of histiocytes imparts a granulomatous appearance but distinct granulomas are not formed
- non-specific chronic interstitial inflammation
- intratubular localization of inflammation in granulamatous orchitis aids in its distinction from infectious granulomas and sarcoidosis (interstitial)
- necrosis is NOT seen
Autoimmune orchitis
- rapid onset testicular enlargement in middle aged men
- may be associated with febrile illness
- granulomas without organisms
Testis - Regression
V - Vascular conditions bring to mind varicoceles, which cause atrophy on the side of the dilated veins
I - Inflammation recalls the atrophy following mumps orchitis and other causes of epidydimoorchitis
N - Neoplasms sugest the atrophy that occurs in the estrogen treatment of prostatic carcinoma
D - Degenerative suggests the atrophy resulting from aging
I - Intoxication should remind one of the atrophy resulting from chronic alcholism, Laennec cirrhosis, and hemochromatosis (x-ray exposure may also produce atrophy)
C - Congenital recalls undescended testes and torsion
A - Autoimmune and allergic suggest nothing
T - Trauma reminds one of the atrophy following vasectomy & accidental ligation of the blood supply during hernia repair
E - Endocrine suggests the atrophy of hypopituitarism, Klinefelter syndrome, & other eunuchoidal states
Testis - Torsion
- twisting of the spermatic cord, leading to ischemia and venous stasis
- may be related to trauma, but frequently the inciting event is obscure
- predisposing anatomic abnormality which allows the testis excess mobility within the scrotum (bell clapper phenomenon), may be bilateral, which is why there is a risk of contra lateral torsion in a patient who has torsion
- true urologic emergency, since surgery within 4-6 hrs may save testis, after that hemorrhagic infarction with obliteration of the testis is inevitable if reduction of torsion is too late
Testicular Neoplasms: Germ Cell Tumors
- Seminomas
- Embryonal Carcinoma
- Yolk sac tumor
- Choriocarcinoma
- Teratoma
Seminomas
- 50% of germ cell tumors
- most common germ cell tumor to occur in “pure” form
- grossly homogeneous, not typically necrotic or hemorrhagic
- microscopically has characteristic distinct cell membrane and clear cytoplasm
- 15% produce human chorionic gonadotropin (HCG)
Embryonal Carcinoma
- occasionally a pure tumor, but much more commonly a component of a mixed germ cell tumor
- more aggressive than seminomas
- grossly more likely to be hemorrhagic or necrotic
- microscopically shows sheets, alveoli, tubules or papillary formations - generally anaplastic looking cells
Yolk Sac Tumor
- endodermal sinus tumor
- almost exclusively a tumor of infants and children up to 3 years of age
- in adults, more commonly seen mixed with other germ cell tumor patterns
- main distinguishing features is production of alpha fetoprotein (AFP) which serves as a serum marker
- immunohistochemical stain is positive for alpha fetoprotein
Choriocarcinoma
- only 1% of germ cell tumors are pure chorio, but chorio is commonly represented in mixed germ cell tumors
- highly aggressive
- mimics the histology of normal placenta (syncitiotropoblasta & cytotrophoblasts) & produces HCG (tumor marker)
- grossly & microscopically very vascular, metastases bleed easily
Teratoma
- more common in children, rare in adulats, commonly mixed with other germ cell type tumors in adults
- mature types (with adult tissues) and immature types with (fetal tissues) exist
- tissue represents more than one germ layer
- may be grossly quite large with variegated color and texture (cysts are common)
Prostate
- retroperitoneal gland which encircles the neck of the bladder
- composed of glandular cells within a supporting stroma; the glands produce secretions which constitute seminal fluid
- the gland is divided into peripheral, central, transitional, and periurethral zones (hyperplasia arises in the transitional and periurethral zones whereas carcinoma arises in the peripheral zone)
Prostate: Microscope
Prostate glands have two types of epithelium, luminal and basal; these may be distinguished on H and E stain, though they are not always obvious. The luminal cells are responsible for producing seminal fluid and express prostate specific antigen, a serine protease which liquefies the seminal fluid coagulum. An immunoperoxidase stain for PSA (right upper panel) decorates the luminal epithelium. The basal cells do not produce PSA
Prostate Inflammation
- acute & chronic bacterial prostatitis and chronic abacterial prostatitis are general categories
- also gonorrhea can cause it
Acute Bacterial prostate inflammation
-usually urinary tract pathogens such as E. coli (other gram negative rods), Enterococci, Staph
Chronic Bacterial Prostate Inflammation
- same organisms as acute bacterial, but more indolent course
- common history of UTI
Chronic Abacterial Prostate Inflammation
- same course as chronic bacterial but organisms more difficult to identify
- ex: mycoplasma, ureaplasma, and chlamydia
Prostate Hyperplasia
- nodular hyperplasia (benign) - androgen driven
- results from hyperplasia of prostatic glands & stroma
- main symptoms relate to bladder obstruction and urinary stasis
- 70% of 60 y/o, 90% of 70 y/o, many asymptomatic
- > 400,000 resections performed annually
Prostate Carcinoma
- most common cancer in men
- 300,000 new cases yearly, 40,000 deaths
- rare under 50, at 70, 70% have at least latent
- most tumors never progress, or do so very slowly
- Japan 3-4/100,000, white 50-60/100,000 more in black
Prostate Carcinoma Etiology
- Androgen related - but there is no correlation of testosterone levels to risk prostate carcinoma
- Genetically & ethnically related, but only minority of cases (10%) can be linked to inheritance of germline susceptibility genes
- Environmentally related—but low risk ethnic groups (Japanese) who move where high risk groups live (America) only modestly increase their risk
Prostate Carcinoma Diagnosis
-physical exam or PSA elevation in blood (both may be done if over 60)
PSA
organ (prostate) specific, but not cancer specific
- rises in in a number of benign conditions, including BPH and prostatitis
- Biopsy is essential to make the diagnosis
AUA Screening Recommendation
- no screening under 40
- individualized decisions about screening for men under 55 at higher risk (AA or positive family history)
- greatest screening benefit ages 55-69
- every two year screening may be preferred to annual screening
- no routine screening after age 70
Prostate Carcinoma Microscope
- can be nearly benign glands to highly anaplastic malignant cells
- back to back glands in crowded, disorganized pattern
- perineural invasion
- extracapsular externsion of the tumor
Gleason Grading System
- for prostate carcinoma
- Grade 1 - best differentiated
- Grade 6 - worst
- add grade from 2 most prevalent patterns (best score is 2, worst is 10)
Prostate Carcinoma Metastases
-bone (almost always osteoblastic rather than osteolytic)