Pathology - male genital Flashcards
1
Q
Hypospadias
A
- Opening of urethra on inferior surface of penis
- Due to failure of urethral folds to close
2
Q
hypospadias - cause
A
Due to failure of urethral folds to close
3
Q
Epispadias
A
- Opening of urethra on superior surface of penis
- Due to abnormal positioning of the genital tubercle
- associated with bladder exstrophy
4
Q
Epispadias - cause
A
Due to abnormal positioning of the genital tubercle
5
Q
What is the difference between hypospadias and epispadias?
A
Hypo = low/below –> due to failure of urethral folds to close (inferior surface defect)
Epi = up/above –> due to abnormal positioning of genital tubercle (superior surface defect)
6
Q
Condyloma acuminatum
A
Benign warty growth on genital skin
Due to HPV type 6 or 11 – characterized by koilocytic change
7
Q
Condyloma acuminatum - what is the cause?
A
Due to HPV type 6 or 11 – characterized by koilocytic change
8
Q
HPV - high risk vs low risk serotypes
A
High risk - 16, 18, 31, 33 –> risk for carcinoma
Low risk - 6, 11 –> usually results in benign lesions (ie condyloma acuminatum)
9
Q
Chlamydia trachomatis - serotypes and respective diseases
A
Serotype A–C: trachoma
Serotype D–K: urogenital abnormalities & conjunctivitis
Serotype L1-L3: lymphogranuloma venereum
10
Q
Lymphogranuloma venereum
A
- Necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes
- Sexually transmitted disease caused by Chlamydia trachomatis
- Eventually heals w/ fibrosis
- Perianal involvement may result in rectal stricture
11
Q
What bug is responsible for lymphogranuloma venereum?
A
Chlamydia trachomatis - serotypes L1-L3
12
Q
lymphogranuloma venereum - prognosis
A
Eventually heals w/ fibrosis
Perianal involvement may result in rectal stricture (narrowing)
13
Q
Squamous cell carcinoma of penis
A
- Malignant proliferation of squamous cells of penile skin
- Risk factors
- high risk HPV (2/3 of cases) - 16,18,31,33
- Lack of circumcision - foreskin acts as a nidus for inflammation and irritation if not properly maintained
- Percursor insitu lesions
- Bowen disease
- Erythroplasia of Queyrat
- Bowenoid papulosis
14
Q
Squamous cell carcinoma of penis - risk factors
A
- high risk HPV (2/3 of cases) - 16,18,31,33
- Lack of circumcision - foreskin acts as a nidus for inflammation and irritation if not properly maintained
15
Q
Why is lack of circumcision a risk factor for squamous cell carcinoma?
A
Foreskin acts as a nidus for inflammation and irritation if not properly maintained
16
Q
Percursor in-situ lesions to squamous cell carcinoma of penis
A
- Bowen disease - in situ carcinoma of the penile shaft or scrotum that presents as leukoplakia. Typically progresses to invasive carcinoma
- Erythroplasia of Queyrat - in situ carcinoma on 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 and erythroplasia of Queyrat
- Does NOT progress to invasive carcinoma
17
Q
Bowen disease
A
in situ carcinoma of the penile shaft or scrotum that presents as leukoplakia.
Typically progresses to invasive carcinoma
18
Q
Bowen disease - clinical presentation?
A
leukoplakia of the penile shaft or scrotum
19
Q
Erythroplasia of Queyrat
A
in situ carcinoma on the glans that presents as erythroplakia
20
Q
What is the main difference between Bowen disease and erythroplasia of Queyrat?
A
Bowen disease - leukoplakia of the penile shaft or scrotum (base of penis)
Erythroplasia - erythroplakia of the glands of penis
21
Q
Bowenoid papulosis
A
- in situ carcinoma that presents as multiple reddish papules
- seen in younger patients (40s) relative to Bowen disease and erythroplasia of Queyrat
- Does NOT progress to invasive carcinoma
22
Q
Difference between Bowen disease and Bowenoid papulosis?
A
Bowenoid papulosis is Bowen-like.
However, Bowenoid papulosis is:
- seen in younger patients
- erythroplasia instead of leukoplakia
- Does NOT progress to invasive carcinoma
23
Q
Testicle development
A
Develops in the abdomen and descends into the scrotal sac as the fetus grows
24
Q
Most common congenital male reproductive abnormality
A
Cryptorchidism (failure of testicle to descend into the scrotal sac)
seen in 1% of male infants
Most cases resolve spontaneously
25
Cryptorchidism
Failure of testicles to descend into the scrotal sac
Most cases resolve spontaneously
Treatment is orchipexy performed before 2 years of age
Complications include testicular atrophy w/ infertility and increased risk of seminoma
26
Cryptorchidism - treatment
Most cases resolve spontaneously
If not, orchiopexy is performed before 2 years of age
27
Cryptorchidism - complications
testicular atrophy w/ infertility
increased risk for seminoma
28
Orchitis
Inflammation of the testicle
29
Orchitis - causes
1. *Chlamydia trachomatis* (serotypes D-K) or *Neisseria gonorrhoeae*
* Seen in young adults
* increased risk of sterility, but libido is not affected because Leydig cells are spared
2. *Escherichia coli* and *Pseudomonas*
* seen in older adults
* UTI pathogens spread into the reproductive tract
3. Mumps virus
* seen in teenage males
* increased risk for infertility
* testicular inflammation is usually not seen in children \< 10 years old)
4. Autoimmune orchitis
* characterized by granulomas involving the seminiferous tubules
30
Orchitis cause in young adults?
* Chlamydia trachomatis* (serotypes D-K) or *Neisseria gonorrhoeae*
* increased risk of sterility, but libido is not affected because Leydig cells are spared
31
Orchitis cause in older adults?
* Escherichia* coli and *Pseudomonas*
* These are the most common UTI pathogens and cause orchitis when they spread into the reproductive tract
32
Mumps - where does it normally infection? What other tissues does it infect?
Normally infects the parotid gland
Occasionally infects other tissues
1. meninges --\> asceptic meningitis
2. pancreatitis
3. orchitis
33
If you see a granuloma in the testicle, what comes to mind?
1. TB (will cause necrotizing granuloma)
2. autoimmune orchitis (non-necrotizing granuloma)
34
Testicular torsion
Twisting of the spermatic cord --\> leaves the artery open (thick walled), but twist closes off the vein (thin walled) --\> obstruction leads to congestion and hemorrhagic infarction
35
What are 2 requirements of hemorrhagic infarction?
1. Blood going into the space after the tissue dies
2. Loosely organized tissue (so it can flow out as opposed to blowing up)
36
Testicular torsion - most common cause
Congenital failure of testes to attach to the inner lining of the scrotum (via the processus vaginalis) --\> no anchor = easier twisting of the cord
37
Testicular torsion - clinical presentation
Sudden testicular pain
absent cremasteric reflex
38
Varicocele
Dilation of the spermatic vein due to impaired drainage
Seen in a large percentage of infertile males
39
Varicocele - presentation
Scrotal swelling w/ a "bag of worms" appearance
* veins are dilated and seen ont he surface of the scrotum
40
Which side does varicocele normally present? Why? What is the association?
Usually left sided: left testicular vein drains into the left renal vein, while right directly drains into the IVC
Associated with left-sided renal cell carcinoma (loves to invade the renal vein)
41
Why is varicocele seen in a large percentage of infertile males?
Varicocele is basically the pooling of warm blood in the scrotal sac.
This warm blood heats up the testicles (which requires lower temperature to function) and will cause permanent damage to the production of sperm.
42
Hydrocele
Fluid collection within the tunica vaginalis (serous membrane that covers the testicle as well as the internal surface of the scrotum)
43
Hydrocele - common causes?
* In **infants**: incomplete closure of the processus vaginalis leading to communication w/ the peritoneal cavity
* In **adults**: blockage of lymphatic drainage
44
Hydrocele - clinical presentation
Scrotal swelling
* Can be transilluminated (not a mass, but rather a bag of fluid)
45
Testicular tumors - clinical presentation
Present as a firm, **painless** testicular mass that cannot be transilluminated (contrasted to a hydrocele that can be transilluminated)
46
Why do you not biopsy testicular cancers?
1. May seed the scrotum when pulling the testicle out
2. \>95% of cases are geerm cell tumors (which are all malignant and require more than surgical removal)
This is contrary to most tumors that require a biopsy to diagnose
47
Germ cell tumors (5)
1. teratoma
2. embryonal carcinoma
3. choriocarcinoma
4. yolk sac tumor
5. seminoma
Teratoma + embryonal (both embryonic origin)
choriocarcinoma + yolk sac tumor (has to do with development)
seminoma (tumor of germ cells -- mature cells -- best prognosis)
48
Age when most germ cell tumors occur?
15 - 40
49
Germ cell tumors - risk factors
Cryptorchidism
Klinefelter syndrome
50
Germ cell tumor - what is the main division? Why is it made?
Divided into seminoma and nonseminoma.
* Seminoma (55% of cases) are highly responsive to radiotherapy, metastasize late, and have an excellent prognosis
* Non-seminoma (45% of cases) show variable response to treatment and often metastasize early
Think of a seminoma as a cancer of mature cells (or at least the most mature of cells in the testicle) which typically results in the best prognosis
51
Seminoma
* malignant tumor comprised of large cells w/ clear cytoplasm and central nuclei (resemble spermatogonia)
* forms a homogenous mass w/ **no hemorrhage or necrosis**
* rare cases may produce B-hCG (classically associated w/ choriocarcinoma)
* good prognosis -- responds to radiotherapy
52
What is the female equivalent of a seminoma?
dysgerminoma
53
Most common testicular tumor
Seminoma
54
Embryonal carcinoma
* malignant tumor comprised of immature, primitive cells that may produce glands
* Forms a hemorrhagic mass w/ necrosis
* aggressive w/ early hematogenous spread (embryo-like: programmed to move and spread rapidly)
* Chemotherapy may result in differentiation into another type of germ cell tumor (ie teratoma)
* Increased AFP or B-hCG may be present
55
Embryonal carcinoma - prognosis
Poor: aggressive tumor w/ early hematogenous spread
Chemotherapy may result in differentiation into another type of germ cell tumor (ie teratoma)
56
What laboratory findings are associated w/ embryonal carcinoma?
Immature primitive cells that may produce glands
Hemorrhagic mass w/ necrosis
Increased AFP or B-hCG
57
Yolk sac (endodermal sinus) tumor
* Malignant tumor that resembles yolk sac elements
* Most common testicular tumor in children
* Schiller-Duval bodies (glomerulus-like structures) seen on histology
* AFP is characteristically elevated
58
Most common testicular tumor? in children?
Adults: seminoma
children: yolk sac (endodermal sinus) tumor
59
Choriocarcinoma
* Malignant tumor of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue, but villi are absent)
* Spreads early via blood (remember these 2 types of cells are genetically programmed to find and invade blood vessels -- mainly the role of syncytiotrophoblasts)
* B-hCG is characteristically elevated --\> may result in hyperthyroidism or gynecomastia (α-subunit of HCG is similar to that of FSH, LH and TSH)
60
Choriocarcinoma - what is different between the cancer and the normal tissue?
Functional unit of the placenta = villus surrounded by syncytiotrophoblasts and cytotrophoblasts
In cancer form, the 2 cell types are there, but the villus is not present
61
why does choriocarcinoma spread early?
The job of syncytiotrophoblasts is to invade blood vessels (minorly aided by cytotrophoblasts)
62
β-hCG: what are the symptoms due to high levels? Why?
What disease(s) is elevated levels associated with?
Symptoms: hyperthyroidism or gynecomastia
* the α subunit of hCG is similar to that of FSH, LH and TSH so at higher levels, there will be nonspecific activation of those receptors. FSH and LH --\> gynecomastia, TSH --\> hyperthyroidism
Elevated levels is classically associated with choriocarcinoma. However, it can be seen elevated in embryonal carcinomas, teratomas and rarely in seminomas.
63
Teratoma
Tumor composed of mature fetal tissue derived from two or three embryonic layers
* malignant in males, benign in females
* AFP or β-hCG may be increased
64
What is the difference between teratomas in male and females?
Malignant in males. Benign in females.
65
Mixed germ cell tumors
Germ cell tumors are usually mixed
Prognosis is based on the worst component
66
Sex-cord stromal cell types
Sertoli cells (lines the tubules)
Leydig cells (produces testosterone)
67
Sex-cord stromal tumors
Tumors that resemble sex cord stromal tissues of the testicle (sertoli cells or leydig cells)
* Leydig cell tumor
* produces androgen --\> precocious puberty in children or gynecomastia in adults
* Characteristic Reinke crystal seen on histology
* Sertoli cell tumor
* comprised of tubules
* clinically silent
Usually benign
68
What cancer is associated with these crystals?
Reinke crystals
Classically seen in Leydig cell tumors
69
Leydig cell tumor
produces androgen --\> precocious puberty in children or gynecomastia in adults
Characteristic Reinke crystal seen on histology
70
Sertoli cell tumor
comprised of tubules
clinically silent
71
Most common cause of a testicular mass in males \> 60 years old
Lymphoma -- often bilateral
Usually diffuse large B-cell type
72
How to distinguish between acute and chronic prostatitis?
Acute
* due to bacteria
* dysuria w/ fever and chills
* prostatic secretions show WBCs -- w/ + bacteria in culture
Chronic
* dysuria w/ pelvic or low back pain
* secretions show WBCs but negative for bacteria
73
What testicular tumors are associated with elevated β-hCG?
Classically: **choriocarcinoma**
However, can also present in
* seminoma (rare)
* embryonal carcinoma
* teratoma
74
What testicular tumors are associated with elevated AFP levels?
Characteristically: **yolk sac tumor**
However can present in:
* embryonal carcinoma
* yolk sac tumor
75
What testicular tumor is associated w/ production of glands?
Embryonal carcinoma
76
Prostate
Consists of glands and stroma
* glands are composed of an inner layer of luminal and an outer layer of basal cells
* secret **alkaline, milky fluid** that is added to sperm and seminal vesicle fluid to make semen
* glands and stroma are maintained by androgens
Prostate is a small, round organ that lies at the base of the bladder, encircles the urethra and sits anterior to the rectum (posterior aspect of prostate is palpable by digital rectal exam (DRE))
77
Screening tools for prostate cancer? why are they used?
1. DRE (digital rectal exam)
* prostate sits anterior of the rectum. Posterior aspect of prostate is palpable by digital rectal exam
2. PSA (prostate specific antigen)
* PSA is made by prostatic glands to liquidify semen
* cancer results in hyperplasia of the glands (adenocarcinoma) and will result in PSA levels \> 10ng/ml
78
What are the glands and stroma of the prostate maintained by?
Androgens
79
Acute prostatitis
Acute inflammation of the prostate -- usually due to bacteria (same bugs as orchitis)
* *Chlamydia trachomatis* and *Neisseria gonorrhoeae* in young adults
* *Escherichia coli* and *Pseudomonas* in older adults
Presents as dysuria w/ fever and chills
Prostate is tender and boddy on DRE
Prostate secretions show WBCs -- culture will reveal bacteria
80
acute prostatitis - causes
Same bugs as orchitis
* *Chlamydia trachomatis* and *Neisseria gonorrhoeae* in young adults
* *Escherichia coli* and *Pseudomonas* in older adults
81
acute prostatitis - presentation
Dysuria w/ fever and chills
Prostate is tender and boggy on DRE
Prostatic secretions show WBCs -- culture reveal bacteria
82
Chronic prostatitis
Chronic inflammation of prostate
Presents as dysuria w/ pelvic or low back pain
Prostatic secretions show WBCs, but cultures are negative
83
What happens to PSA as we age?
PSA will increase naturally -- mainly due to benign prostatic hyperplasia (no increase in carcinoma risk)
84
Benign prostatic hyperplasia (BPH)
Hyperplasia of prostatic stroma and glands
age-related change (present in most men by 60 years) -- no increased risk for cancer
Related to DHT (dihydrotestosterone)
* 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
Occurs in the central periurethral zone of the prostate
* growth will cause compression of the urethra --\> clinical features associated with urinary obstruction
Clinical features:
* problems starting and stopping urine stream
* impaired bladder emptying w/ increased risk for infection and hydronephrosis (backup of fluid into the kidney)
* Dribbling
* hypertrophy of bladder wall smooth muscle --\> increased risk for bladder diverticula
* microscopic hematuria may be present
* PSA is often slightly elevated (4-10ng/ml) due to increased number of glands
* PSA is made by prostatic glands and liquefies semen
85
What chemical is responsible for benign prostatic hyperplasia?
* 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
86
where does benign prostatic hyperplasia occur? What is the location's significance?
Occurs in the central periurethral zone of the prostate
This zone surrounds the prostate. Hyperplasia of growth of this zone will compress the urethra resulting in urinary obstruction (which is what the majority of BPH symptoms are a result of)
87
Benign prostatic hyperplasia - clinical features
1. problems starting and stopping urine stream
2. impaired bladder emptying w/ increased risk for infection and hydronephrosis (backup of fluid into the kidney)
3. Dribbling
4. hypertrophy of bladder wall smooth muscle --\> increased risk for bladder diverticula
5. microscopic hematuria may be present
6. PSA is often slightly elevated (4-10ng/ml) due to increased number of glands
* PSA is made by prostatic glands and liquefies semen
88
Hydronephrosis
literal translation: "water in kidney"
Typically results from urinary obstruction and causes backup of fluid into the kidney that can result in dilation and atrophy of the ureter and kidney
89
Why is there hypertrophy of the bladder wall smooth muscle in benign prostatic hyperplasia? What can result due to this?
In BPN, there is narrowing of the urethra which causes increased tension in the bladder resulting in hypertrophy.
The high pressure generated in the bladder against the obstruction could result in diverticuli or outpouching of the bladder wall
90
What is the purpose of PSA? Why is it secreted?
Secreted by prstatic glands to liquefy semen
91
PSA levels? Normal/BPN/adenocarcinoma
**Normal**: 0-4ng/ml
**BPN**: 4-10ng/ml (increases with age from 2.5 at 40-49years to 7.5 at 70-79 years)
**adenocarcinoma**: \> 10ng/ml
92
Benign prostatic hyperplasia - treatment (2)
1. α1-antagonist (ie terazosin) to relax smooth muscle
* also relaxes vascular smooth muscle --\> lowering BP (helps if patient also has HTN)
* selective α1a -antagonists (ie tamsulosin) are used in normotensive individuals to avoid the α1b effects on blood vessels
2. 5α-reductase inhibitor
1. blocks conversion of testosterone to DHT
2. Takes months to produce results
3. also useful for male pattern baldness
4. side effects are gynecomastia and sexual dysfunction
93
Prostate adenocarcinoma
* Malignant proliferation of prostatic glands
* Most common cancer in men -- 2nd most common cause of cancer-related death
* Risk factors include age, race (African Americans \> Caucasians \> asians), and diet high in saturated fats
94
Most common cancer in men
Prostatic adenocarcinoma
95
Prostatic adenocarcinoma - clinical presentation
Most often clinically silent
* Usually arises in the peripheral, posterior region of the prostate, and hence does not produce urinary symptoms early on (only if it cancer grows significantly to compress the urethra)
* because it is silent, it requires screening (DRE and PSA)
96
Prostatic adenocarcinoma - screening
Done with DRE (digital rectal exam) and PSA (prostatic specific antigen)
* screening begins at age 50
* Normal serum PSA increases w/ age due to BPH (normal: 2.5ng/ml @40-49, 7.5ng/ml @70-79)
* PSA \> 10ng/ml highly worrisome at any age
* Cancer only makes bound PSA so decreased %free-PSA is suggestive of cancer
97
What does a decreased % of free PSA mean?
Decreased % free PSA == highly suggestive of cancer
* Cancer makes only bound PSA. Increased bound PSA will decrease the percentage of free PSA.
98
What is required to confirm the diagnosis of prostatic carcinoma?
Biopsy - shows small, invasive glands w/ prominent and dark nucleoi
Graded on the Gleason grading system (based on architexture alone, and NOT on nuclear atypia)
99
Gleason grading system
* based on architexture alone, and NOT on nuclear atypia
* multiple regions of the tumor are assessed because achitecture varies from area to area
* A score of (1-5 is assigned for two distinct areas and then added to produce a final score (2-10)
* Higher score suggests worse prognosis
100
Where is prostatic adenocarcinoma likely to spread? What is the result of the spread?
Like to lumbar spine 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)
101
prostatic adenocarcinoma - treatment
Prostatectomy is performed for localized disease
advanced disease is treated w/ hormone suppression to reduce testosterone and DHT
* continuous GnRH analogs (ie leuprolide) shut down the anterior pituitary gonadotrophs (LH and FSH reduced)
* remember prostate cancer is highly androgen dependent. The cancer loses its ability to thrive by reducing androgens
* Flutamide acts as a competitive inhibitor at the androgen receptor
102
Drugs used to treat prostatic adenocarcinoma
continuous GnRH analogs (ie **leuprolide**) shut down the anterior pituitary gonadotrophs (LH and FSH reduced)
* remember prostate cancer is highly androgen dependent. The cancer loses its ability to thrive by reducing androgens
**Flutamide** acts as a competitive inhibitor at the androgen receptor
