Male Reproductive Pathology - Twomey Flashcards
What are the three important anatomical zones of the prostate? How do these relate to cancer pathology?
Central zone - CZ
25% of gland mass
40% of epithelial cells
5-10% of all carcinomas
Transitional zone - TZ
5% of gland mass
most cases of BPH
rare carcinomas
Peripheral zone - PZ
70% of gland mass
most carcinomas (can palpate on digital rectal exam)
What are the clinical features of acute bacterial Prostatitis?
mostly Gram-negative rods => same organisms as in UTIs
Fever, chills and dysuria
Extremely tender and boggy on exam
Dx. based on urine cx. and clinical features
What are the clinical features of Chronic bacterial Prostatitis?
Same organisms as acute
Non-specific sxs: low back pain, dysuria, pelvic pain or no symptoms
May see recurrent UTI’s with same causative agent
Dx: + prostatic massage cxs. & >5 leukocytes/HPF in prostatic fluid, or increase in UA WBC count post massage
What are the clinical features of Chronic abacterial Prostatitis?
Most common form of prostatitis today
Similar to chronic bacterial, but culture neg.
Usually sexually active men
STD organisms have been implicated => Chlamydia, Mycoplasma, Ureaplasma
What happens to the PSA in prostatitis?
increased PSA
30% of men with prostatitis will have a decreased PSA
How do you treat prostatitis?
Tx with abx, NSAIDS – txment may be ineffective in chronic cases
What is the cause of BPH?
Androgens - dihydrotestosterone production increases in prostate stromal cells with aging – stimulates growth
Estrogens - estradiol levels increase in men with aging – induce an increase in androgen receptors in prostate
What is the incidence of BPH?
40 20% of patients
60 70% of patients
70 90% of patients
50% of men become symptomatic
> 400,000 TURP’s/year by late 80’s in US, less than 1/2 that today with better medical therapy
What is the pathology behind BPH?
primarily in TZ & peri-ureth.
Nodular proliferation of both glands and stroma – not pre-malignant
Which symptom of BPH is most indicative of a problem?
nocturia (peeing at night)
What are the symptoms of BPH?
Hesitancy
Urgency
Frequency
Decreased stream size
Nocturia
Terminal dribbling
How much bigger does the prostate become in BPH?
Normal size in young men – 20g
Average size in BPH sufferers – 33g
4% of men will reach 100g (5x normal)
Largest recorded – 820g
What are the complications of BPH?
Obstruction
Incomplete bladder emptying
Infection
Infarction
Defective bladder fxn due to muscle hypertrophy and stretch
Renal failure
What are the two most common drug treatments of BPH?
5 alpha-reductase inhibitor (Finasteride - Proscar)
(50%+ reduction in PSA,
Multiply PSA X 2.3 if taking 1mg/d >4 years,
25% decrease in prostate Ca., but higher proportion of higher grade cancers)
Alpha-1 blocker (Tamsulosin – Flomax) => Smooth muscle relaxant => instant relief
What are the surgical treatment options for BPH?
TURP, Cryotherapy, Microwave, Laser, US
If a patient presents with a varicocele, what side is it most likely to present on?
Left (drains into the left renal vein)
What are the two phases of Testicular Descent?
Phase 1
Transabdominal
Descends to lower abdomen/pelvic brim
Controlled by mullerian-inhibiting substance
Phase 2
Inguinoscrotal
Descends through the inguinal canal into scrotum
Androgen dependent
What is the incidence of Cryptorchid (abscent) Testis?
25% of premature infants
4-6% of newborns have patent inguinal canal
closed by 3 months in most cases
1-2% cryptorchidism by end of first year
Location: 70% high in scrotum, 20% in inguinal canal, 10% intra-abdominal
Unilateral – 75%
Cause poorly understood – rarely seen in hormonal disorders, see in trisomy 13
Asymptomatic
What are the histological changes seen in Cryptorchid Testis?
Histologic changes as early as 2 years:
- Germ cell arrest
- Basement membrane thickening/hyalinization
- Decreased germ cells in contralateral testis
What is the clinical importance of Cryptorchid Testis?
Sterility if bilateral & uncorrected
Infertility (even if unilateral & uncorrected - implies defective germ cells)
Accompanying hernia 10-20%
Anatomic: increased risk for crush injuries
Oncogenic: 5 to 10-fold increase in germ cell tumors (5-10% of testicular germ cell tumors occur in cryptorchid testes)
What is the treatment for Cryptorchid Testis? Prognosis?
Orchiopexy (procedure to free soft tissue that is holding testis and then suture testis to wall of scrotum)
Before 2 years old for fertility, 10 years for neoplasm
Deficient spermatogenesis still in 10-60%
Some increased risk of cancer remains, even in contralateral testis – intrinsic defect in testicular development & cellular differentiation
What are the different classes of causes for Male infertility?
Hormonally
Testis itself (scarring)
Genetic
Idiopathic (spermatogenic arrest)
Autoimmunity
Varicocele
Drugs (cyclophosphamide)
Post-testicular obstruction
Atherosclerosis
Malnutrition/cachexia
Irradiation
Female sex hormones
What is “Sertoli Cell Only” Syndrome?
germ cell aplasia => Reduced/absent sperm production
10-20% of all testicular biopsies in infertile males
Small to nml. sized testes with azoosp.
What Chromosomal abnormalities can result in male infertility?
Klinefelter and Down syndrome
Infertility With Oligospermia (2 - 20,000,000/ml)
Testicular: many genetic, toxic, endocrine, vascular, infectious causes
Post-testicular: usually obstruction
Key feature: normal testicular biopsy
Post vasectomy - most common
Site of obstruction in non-vasectomy cases:
50% - epididymis,
25% - absence of vas (1% of infertile males),
10% - obstruction of vas or ejaculatory ducts,
40% of male infertility is idiopathic
What are the causes of Epididymo-orchitis?
Bacterial = Related to UTI’s – spread through vas deferens or lymphatics
Under 35 yrs. old most are sexually transmitted (Neisseria gonorheae, Chlamydia, Mycoplasma, Treponema Pallidum (1T) )
Older than 35 usually associated with recurrent UTI’s or BPH - coliform bacteria
Granulomatous => Tuberculosis uncommon today; typically involves epididymis
Non-tuberculous – unilateral, autoimmune?
Viral - several implicated (Mumps – testes rarely involved pre-pubertal, 20-30% post-pubertal, 2/3 unilateral)
What pathologies should you think about when you see granuloma formation (single multi-nucleated giant cell) on a histological slide of the testis?
TB or fungal (histo-, crypto-, or coccidio-)
What are the two vascular disturbances that can occur in the male genitalia?
Torsion and Varicocele
What are the clinical features of Torsion?
testicle rotates, twisting the spermatic cord that brings blood to the scrotum (Venous > arterial)
Usually before age 30 – can see as early as 1 yr old
Causes - violent motion or trauma, usually in setting of abnormal anatomy ( incomplete descent, atrophy etc.)
Many cases have no history of a defining event
Hemorrhagic infarction - surgical repair within 4 hours may salvage function
What are the clinical features of Varicocele?
dilation of veins within pampiniform plexus (“bag of worms”)
Incidence: up to 25% of adults
More common on left side; 10-15% bilateral
A cause of infertility (relative hyperthermia, others)
Germ Cell Tumors
Seminoma
Embryonal carcinoma
Yolk sac tumor
Teratoma
Choriocarcinoma
Sex cord stromal tumors
Sertolic cell tumor
Leydig cell tumor
Granulosa cell tumor
Mixed
What is the Seminomatous Testicular tumor that is more localized and has a better prognosis than non-seminomatous tumors?
What are the four non-Seminomatous that are more likely to metastasize?
Seminomatous = Seminoma
Non-Seminomatous = Embyronal, Yolk sac, Teratoma, Choriocarcinoma
What is the incidence of germ cell tumors?
Incidence - appears to be rising
1-3% of all malignancies in men
30% of all malignancies in age group 20 - 34 yr
Most common solid tumor in men 15-34
Varies by location and ethnic group
6/100,000 in US, highest in Denmark and adjacent
countries
5:1 white:black ratio
7,000 new cases in US/yr; 6,900 in testis, 300 deaths
Most cases are non-familial and no major gene linkages are apparent
What is the precursor lesion in testicular cancer?
“Intratubular germ cell neoplasia” (CIS) - data from Denmark
0.8 % of all males
2-3 % with cryptorchidism
> 25% with androgen insensitivity syndrome/gonadal dysgenesis/feminization syndrome (no androgen receptors)
What are the clinical features of testicular germ cell tumors?
Progressive, painless testicular enlargement
Bilateral in 1- 3%; up to 15% in bilateral cryptorchidism
can have different phenotypic expression
lymphoma is most likely cause in older males (>40’s)
What are the clinical featurs of Seminoma tumors?
50% of all germ cell tumors
***Peak in 30’s
Rare in children
Ovary - dysgerminoma
Phenotypic expression: Typical seminoma—95%, Spermatocytic seminoma—5%
What are the histological features of Seminoma tumors?
clear cytoplasm (lots of white)
lots of lymphocytes
lot of fibrous tissue
occasional non-caseating granulomas
some syncytiotrophoblast cells (secrete Beta-hCG => can use as tumor marker)
What are the clinical features of Embryonal Carcinoma?
2nd most frequent form of pure GCT
***20-30 year age group
More aggressive than seminoma
Rare before puberty or after 50
Grossly smaller than seminoma because they are found earlier
Pain/twinge => will precede finding a lump
What are the histological features of Embryonal tumors?
More pleomorphisms
Dark nuclei, more mitotic activity
Hemorrhage
What are the clinical featurs of Yolk Sac Tumors?
Most common testicular tumor in infants/young children under 3 years, in pure form
Clear cells recapitulating endodermal sinus
Schiller-Duval bodies (ring of cells, “yolk sac” appearing) and lobules of protein (pink)
Marker—aFP (alpha-feta protein)
What are the clinical features of Choriocarcinoma?
Highly malignant (spread hematogenously)
Rare in pure form -
What are the clinical featurs of Teratomas?
Recapitulates tissue from >1 germ cell layer
Infancy to throughout adulthood
Pure form common in infancy/childhood, rare in adults
Mature, immature, malignant forms
***Never benign in adult males
What are the gross and histological features of Teratomas?
cysts (endodermal tract linings)
fat (mesodermal layer)
skin (multiple forms of epithelium)
What are the clinical features of Mixed Testicular Tumors?
60% of testicular tumors
Prognosis worsens with inclusion of more aggressive forms
Pattern of metastases:
- Lymphatic spread (Retroperitoneal (aorta), Mediastinal and supraclavicular nodes)
- Hematogenous spread (Lung, brain, liver, other organs common depending on tumor phenotype)
Metastasis histology may differ from primary
Seminomatous component of mixed tumors usually does not metastasize
What is the basic Staging of Testicular Cancer?
Stage I: Local spread (rarely spreads beyond tunica albuginea - Ic)
Stage II: Involvement of retroperitoneal lymphatics
Stage III: Parenchymal metastases or nodes beyond retroperitoneal
What is the treatment for Seminomas?
exquisitely radiosensitive
Stage I – orchiectomy alone with W.W.
Stage II – orchiectomy and pelvic/paraortic LN XRT or orchiectomy and single agent chemo -cisplatin
What are the two Non-Germ Cell Testicular Tumors?
Sertoli cell Tumor: Several variants - often admixed with granulosa cells, Associated with gynecomastia
Leydig cell Tumor: elaborate androgens and/or estrogens
1-3% of tumors, Adults with gynecomastia
Testicular lymphoma
5% of tumors
Older adults, >60
Usually large cell histology and systemic disease
What is a hydrocele?
cystic space obliterated on each end
What is a Spermatocele?
cystic mass arising from efferent ducts
lumen filled with sperm
