Week 4: Male genital system pathology Flashcards
What is Hypospadias?
Opening of the urethra on the inferior surface of the penis
Etiology/Pathophysiology of hypospadias
Due to failure of the urethral folds to close
What is epispadias?
Opening of the urethra on the superior surface of the penis
Etiology/Pathophysiology of epispadias
due to abnormal positioning of the genital tubercle
Epispadias associations
Associated with bladder exstrophy
What is Condyloma acuminatum?
Benign warty growth on genital skin
Etiology of Condyloma acuminatum
Due to HPV 6 or 11
Histological features of Condyloma acuminatum
Characterized by Koilocytic change
What is Lymphogranuloma venerum?
Necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes
Lymphogranuloma venerum etiology
Sexually transmitted disease caused by Chlamydia trachomatis (serotypes L1-L3)
Prognosis of Lymphogranuloma venerum
- Eventually heals with fibrosis
- perianal involvement may result in rectal stricture
What is male genital squamous cell carcinoma?
Malignant proliferation of squamous cells of penile skin
Risk factors for male genital squamous cell carcinoma
- High risk HPV (2/3 cases)
- Lack oof circumcision - foreskin acts as a nidus for inflammation and irritation if not properly maintained
Precursor lesions of male genital squamous cell carcinoma
- Bowen disease - in situ carcinoma of the penile shaft or scrotum that presents as leukoplakia
- Erythroplasia of Queyrat - in situ carcinoma of the glans that presents as erythroplakia
- Bowenoid papulosis - in situ carcinoma that presents as multiple reddish papules
- seen in younger patients (40s) relative to Bowen disease or Erythroplasia of Queyrat
- Does NOT progress to invasive carcinoma
Some forms of testicular pathology
- Cryptorchidism
- Orchitis
- Testicular torsion
- Variocele
- Hydrocele
- Testicular tumors
- Germ cell tumors
- sex cord-stromal tumors
- Lymphoma
What is Cryptorchidism?
- Failure of the testicle to descend into the scrotal sac
- testicles normally develop in the abdomen and then “descend” into the scrotal sac as the fetus grows
Epidemiology of Cryptorchidism
The most common congenital male reproductive abnormality (1% of male infants)
Prognosis of Cryptorchidism
- Most cases resolve spontaneously
- otherwise: Orchiopexy is performed before 2 years of age
Complications of Cryptorchidism
- testicular atrophy with infertility
- increased risk for seminoma
What is Orchitis?
Inflammation of the testicle
Common etiologies of Orchitis
- Chlamydia trachomatis (serotypes D-K)
- Neisseria gonorrhoeae
- Escherichia coli
- Pseudomonas
- Mumps virus
- Autoimmune orchitis
Features of orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae
- seen in young adults
- increased risk of sterility
- Libido not affected because Leydig cells are spared
Features of orchitis caused by Escherichia coli and Pseudomonas
- seen in older adults
- urinary tract infection pathogens spread into the reproductive tract
Features of orchitis caused by mumps virus
- occurs in teenage males
- increased risk for infertility
- testicular inflammation is usually not seen in children < 10 years old
Features of orchitis caused by Autoimmunity
- Characterized by granulomas involving the seminiferous tubules
What is testicular torsion?
- Twisting of the spermatic cord
- thin-walled veins become obstructted leading to congestion and hemorrhagic infarction
testicular torsion etiology
Usually due to congenital failure of testes to attach to the inner lining of the scrotum (via the processus vaginalis)
testicular torsion clinical presentation
presents in adolescents with sudden testicular pain and absent cremasteric reflex
What is Varicocele?
Dilation of the spermatic vein due to impaired drainage
Varicocele clinical presentation
- presents as scrotal swelling with a “bag of worms” appearance
- Usually left-sided
- Left testicular vein drains into the left renal vein while the right testicular vein drains directly to the IVC
Varicocele risk factors
Seen in a large percentage of infertile males
Varicocele which side and why?
- Usually left-sided
- Left testicular vein drains into the left renal vein while the right testicular vein drains directly to the IVC
Varicocele associations
Associated with left-sided renal cell carcinoma, RCC often invades the renal vein
What is Hydrocele?
- Fluid collection within the tunica vaginalis
- the tunica vaginalis is a serous membrane that covers the testicle as well as the internal surface of the scrotum
Hydrocele etiologies
Associated with incomplete closure of the processus vaginalis leading to communication with the peritoneal cavity (infants) or blockage of lymphatic drainage in adults
Types of Testicular tumors
- germ cell tumors
- Sex-cord stroma tumors
- lymphomas
Basic presentation of testicular tumors
- Presents as a firm, painless testicular mass that cannot be transilluminated
- Usually not biopsied due to risk of seeding the scrotum
- Removed via radical orchiectomy
- Most testicular tumors are malignant germ cell tumors
Epidemiology of germ cell tumors
- The most common type of testicular tumor ( >95% of cases)
- usually occur between 15-40 years of age
Risk factors for germ cell tumors
- Cryptorchidism
- Kleinfelter syndrome
Types of germ cell tumors
- Seminoma
- Nonseminoma
Features of seminoma germ cell tumors
- 55% of cases (most common testicular tumor)
- Often resembles ovarian dysgerminoma
- highly responsive to radiotherapy
- metastasize late
- excellent prognosis
- Rare cases may produce β-hCG
Features of nonseminoma germ cell tumors
- 45% of cases
- show variable response to treatment and often metastasize early
Histological features of seminoma germ cell tumors
a malignant tumor comprised of large cells with clear cytoplasm and central nuclei (resemble spermatogonia) forms a hemogeneous mass with no hemorrhage or necrosis
Histological features of Embryonal carcinoma
- malignant tumor comprised of immature, primtive cells that may produce glands
- forms a hemorrhagic mass with necrosis
Types of nonseminiferous germ cell tumors
- Embryonal carcinoma
- Yolk sac tumor
- Choriocarcinoma
- Teratoma
- mixed germ cell tumors
Features of Embryonal carcinoma
- a malignant nonseminiferous germ cell tumor
- aggressive with early hematogenous spread
- chemotherapy may result in differentiation into another type of germ cell tumor (eg teratoma)
- Increased AFP or β-hCG may be present
What is the most common testicular tumor in children
Yolk sac tumor
Histological features of Yolk sac tumor
- malignant tumor that resembles yolk sac elements
- Schiller-Duval bodies (glomerulus-like structures)
Features of Yolk Sac tumor
- Most common testicular tumor in children
- Schiller-Duval bodies (glomerulus-like structures) seen on histology
- AFP is characteristically elevated
What is AFP?
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4. AFP is a major plasma protein produced by the yolk sac and the fetal liver during fetal development. It is thought to be the fetal analog of serum albumin.
Histological features of Choriocarcinoma
- malignant tumor of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue but villi are absent)
Features of Choriocarcinoma
- malignant nonseminiferous germ cell tumor composed of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue but villi are absent)
- early hematogenous spread
- β-hCG is characteristically elevated
- may lead to hyperthyroidism or gynecomastia (α-subunit of hCG is similar to that of FSH, LH and TSH)
Testicular tumor that can produce β-hCG
- Rare cases of Seminoma germ cell testicular tumor
- Embryonal carcinoma
- Choriocarcinoma
- Teratoma
Histological features of Teratoma
tumor composed of mature fetal tissue derived from two or three embryonic layers
Features of Teratoma
- malignant germ cell tumor that is composed of mature fetal tissue derived from two or three embryonic layers
- Malignant in males (not in females)
- AFP or β-hCG may be increased
Features of mixed-germ cell tumors
- Germ cell tumors are usually mixed
- Prognosis is based on the worst component
Describe Sex cord-stromal tumors
- Tumors that resemble sex cord-stromal tissues of the testicle
- Usually benign
- Leydig cell tumor usually produces androgen, causing precocious puberty in children or gynecomastia in adults
- Sertoli cell tumor is comprised of tubules and is usually clinically silent
Sex-cord stromal tumors histological features
Leydig cell tumor - Reinke crystals may be seen on histology
What is the most common cause of testicular mass in males > 60 years old?
Lymphoma
Features of Lymphoma testicular tumors
- often bilateral
- most common cause of testicular mass in men > 60 years old
- Usually of diffuse large B-cell type
Basic description of the prostate
- small round organ that lies at the base of the bladder encircling the urethra
- Sits anterior to the rectum; posterior aspect of prostate is palpable by digital rectal exam (DRE)
- Consists of glands and stroma
- glands are composed of an inner-layer of luminal cells and an outer layer of basal cells; secrete alkaline, milky fluid that is added to sperm and seminal vescile fluid to make semen
- Glands and stroma are maintained by androgens
What is acute prostatitis?
Acute inflammation of the prostate, usually due to bacteria
Etiology of acute prostatitis
- Chlamydia trachomatis (young adults)
- Neisseria gonorrhoeae (young adults)
- Escherichia coli (older adults)
- Pseudomonas (older adults)
Clinical presentation of Acute prostatitis
- Presents as dysuria with fever and chills
- prostate is tender and boggy on DRE
- prostatic secretions show WBCs, culture reveals bacteria
What is chronic prostatitis?
Chronic inflammation of the prostate
Clinical presentation of Chronic prostatitis
- dysuria with low back or pelvic pain
- prostatic secretions show WBCs, cultures are negative
What is BPH?
Benign prostatic hyperplasia
- Hyperplasia of the stroma and glands
- Age-related change (present in most men by the age of 60)
- no increased risk for cancer
BPH etiology
- BPH is related to dihydrotestosterone (DHT)
- Testosterone is converted to DHT by 5α-reductase in stromal cells
- DHT acts on the androgen receptor of stromal and epithelial cells resulting in hyperplastic nodules
Clinical features of BPH
- Occurs in the central periurethral zone of the prostate
- problems starting and stopping urine stream
- Impaired bladder emptying with increased risk for infection and hydronephrosis
- Dribbling
- Hypertrophy of bladder wall smooth muscle (increased risk for bladder diverticula)
- microscopic hematuria may be present
- PSA is often slightly elevated (usually less than 10 ng/mL) due to the increased number of glands
- PSA is made by prostate glands and liquefies semen
Treatment of BPH
- α1-antagonists (eg Terazosin) to relax smooth muscle
- also relaxes vascular smooth muscle lowering blood pressure
- Selective α1A-antagonists (eg tamsulosin) are used in normotensive individuals to avoid α1B effects on blood vessels
- 5α-reductase inhibitor (eg finasteride)
- blocks conversion of testosterone to DHT
- takes months to produce results
- also useful for male pattern baldness
- side effects are gynecomastia and sexual dysfunction
What is Prostate adenocarcinoma?
Abnormal proliferation of prostatic glands
Prostate adenocarcinoma epidemiology
- Most common cancer in men
- 2nd most common cause of cancer-related death
Risk factors of Prostate adenocarcinoma
- Age > 50 years
- African American > Caucasians > Asians
- diet high in saturated fats
Clinical presentation of Prostate adenocarcinoma
Prostatic carcinoma is often clinically silent
- usually arises in the peripheral, posterior region of the prostate and, hence, does not produce urinary symptoms early on
- Screening begins at the age of 50 with DRE and PSA
- normal PSA levels increase with age due to BPH (2.5 ng/mL for ages 40-49 vs 7.5 ng.mL for 70-79 years)
- PSA > 10 ng/mL is worrisome at any age
- Decreased % free PSA is suggestive on cancer (cancer makes bound PSA)
Diagnosis of Prostate adenocarcinoma
- Biopsy is required to confirm the presence of carcinoma
Histological features of Prostate adenocarcinoma
- small invasive glands with prominent nucleoli
Gleason score of Prostate adenocarcinoma
Gleason grading is based on architecture alone (not nuclear atypia)
- Multiple regions of the tumor are assessed because architecture can vary from area to area
- A score of (1-5) is assigned for two distinct areas then added to produce a final score of (2-10)
- The higher the score, the worse the prognosis
Prostate adenocarcinoma common spread sites
- Spread to bone of lumbar or pelvis is common
- Results in osteoblastic metastases that present as low back pain and increased serum alkaline phosphatase, PSA and prostatic acid phosphatase (PAP)
Prostate adenocarcinoma treatment
- Prostatectomy is performed for localized disease
- Advanced disease is treated with hormone suppression to reduce testosterone and DHT
- continuous GnRH analogs (eg Leuprolide) shit down anterior pituitary gonadotrophs (LH and FSH are reduced)
- Flutamide acts as a competitive inhibitor at the androgen receptor
