14 - Genital system diseases

Question 1

Nodular Hyperplasia of Prostate (NHP = BPH) (Epidemiology, Etiology, Morphology)

Answer 1

1. Epidemiology
   a. Age at onset – often by forties
   b. Incidence – extremely common
   1) Incidence increases with age.
   2) 90% men have BPH by age 70 years!
2. Etiology
   a. Involves balance of cholesterol-based hormones.
   b. Seen when testosterone drops with age and is outweighed by estrogen.
   c. Seen when balance of androgens shifts from testosterone towards dihydrotestosterone.
   5α-reductase - Testosterone > DHT > enlargement
3. Morphology
   a. Glandular and stromal hyperplasia (glandular AND muscular tissue)
   b. Involves central zone (major area) of prostate gland surrounding the urethra.

Question 2

Carcinoma of the prostate (Epidemiology, Etiology)

Answer 2

1. Epidemiology

a. Incidence
1) Incidence increases with age.
2) Most common cancer in men and second leading cause of cancer deaths in men.

b. Age and race predilection
1) Generally after age 50 years; peak incidence is 65 to 75 years.
2) If a man lives long enough, he will get it!
3) Blacks are affected twice as commonly as non-blacks.
Carcinoma of the Prostate, continued

2. Etiology
   a. Combined hormonal, genetic and environmental factors are thought to be involved.
   b. Androgens play an important role – nodular prostatic hyperplasia does not increase risk!
   Polymorphism in androgen receptors
   diets high in animal fats increase risk

Question 3

Carcinoma of the prostate (Behavior, treatment, prognosis)

Answer 3

5. Behavior
   a. Metastasizes first to local lymph nodes.
   b. Commonly metastasizes to lumbar vertebrae.
   Lumbar vertebrate > fracture > BACK PAIN
   c. Bone metastases produce elevated serum acid phosphatase.
   Invasive. Can be indolent to aggressive.
6. Treatment
   a. Surgery – sexual side effects are common
   b. Radiation – conventional and proton beam
   c. Hormonal – orchiectomy, estrogens
   Reduce testosterone > supplement w/ estrogen (may cause breast development)
7. Prognosis
   a. 90% 10-year survival for T1 and T2 lesions
   b. 10-40% 10-year survival for disseminated disease
   Varies significantly by stage (TNM). Earlier dx, better prognosis

Question 4

Testicular neoplasms (Epidemiology, Origins, Etiology)

Answer 4

1. Epidemiology
   a. Occur in 2:100,000 males.
   b. Age predilection – peak incidence between ages 15- and 34-year-olds
2. Origins
   a. 95% are derived from germ cells. These are almost always malignant.
   b. 5% are derived from interstitial cells – usually benign
3. Etiology – isochromosome of chromosome 12 is common.

Question 5

Testicular neoplasms (S/S, Tx, prognosis)

Answer 5

6. Clinical Signs and Symptoms
   a. Persistent painless testicular enlargement
   b. Metastasize to lungs, brain and bones.
   Asymmetry of testicles, fleshy nodule
7. Treatment
   a. Depends on histologic type
   b. Options include orchiectomy, radiation therapy and chemotherapy.
   Chemo very effective tx, even in late stage.
8. Prognosis – depends on histologic type
   a. Best prognosis – seminoma, even with metastases
   b. About 95% long-term survival overall.

Question 6

SCC of uterine CERVIX (Etiology)

Answer 6

b. Etiology
1) Sexually transmitted disease – strongly linked to HPV types 16 and 18
a) There are now vaccines available for prevention of HPV.
•Guardasil prevents HPV types 6, 11, 16 and 18.
•Cervarix prevents HPV types 16 and 18.
b) HPV Types 16 and 18 are linked to 70% of cases of cervical cancer.
c) HPV Types 6 and 11 cause 90% of cases of genital warts
2) Often preceded by dysplasia – cervical intraepithelial neoplasm = CIN
Dysplasia = full thickness of epi > cancer, but not in CT or past basal cell layer. Dysplasia = precursor lesion of SCC

Question 7

Leiomyomas (Fibroids) of the UTERINE BODY (Epidemiology, Etiology)

Answer 7

1. Benign uterine tumor of smooth muscle origin (myometrium)
   Fibroid tumor
2. Epidemiology
   a. Occur in 1 of 4 women.
   b. Most common tumor in adult women
   Most common tumor (neoplasm) in women, in GENERAL!
3. Etiology – appear to be estrogen dependent.

Question 8

Endometrial hyperplasia (Etiology, Classification)

Answer 8

Most common CANCER of GENITAL SYSTEM in women
1. Etiology
a. Hyperestrinism, especially unopposed estrogen
Excess estrogen > hyperplasia of uterine lining
b. Exogenous estrogens
c. Synthetic estrogens
Estrogen = inc proliferation
Progesterone = inc maturation

2. Classification
   a. Severity – mild, moderate or severe
   b. Atypia – increases risk for endometrial carcinoma.

Question 9

ENDOMETRIAL CARCINOMA (Epidemiology, Risk factors)

Answer 9

1. Epidemiology (Invasive!)
   a. 4th most common cancer of women, accounting for 6% of cancers in women
   b. Most common cancer of the female genital tract
   c. Responsible for only 3% of cancer deaths in women.
   d. Occurs most commonly in post-menopausal women 55-65 years old.
2. Risk factors
   a. Obesity (make + store estrogen)
   b. History of infertility (unopposed estrogen, missed periods)
   c. Diabetes mellitus
   hypertension. Things that increase estrogen

Question 10

OVARIAN NEOPLASMS (Clinical characteristics of group, morphological types)

Answer 10

1. Clinical Characteristics for the Group
   a. Usually are asymptomatic until quite large, and most are not found until late stage.
   b. Only 30% are found on routine pelvic exam.
   c. Large tumors may cause pain or pelvic pressure.
   d. Overall, 5-year survival is 30-35%
   e. Ovarian cancer is the most lethal cancer of the female genital tract!
2. Morphologic Types of Ovarian Neoplasms
   Surface germinal epithelium tumors = SEROUS TUMORS, MUCINOUS TUMORS
   Germ cell tumors = Teratoma, Choriocarcinoma

Question 11

Surface germinal epithelium tumors (SEROUS)

Answer 11

Surface germinal epithelium tumors = 65-70%
(90% malignant)
1) SEROUS TUMORS
a) MOST COMMON TYPE OF OVARIAN TUMORS
• Borderline/malignant tumors account for 40% of all ovarian cancers.
b) Occur in later fertile years – thirty something.
Large fluid filled cavities, fluid > tissue
c) Serous tumors exhibit a wide range of behavior.
• 60% are benign (thin wall)
• 15% are borderline = low malignant potential (difficult to tx, predict. growth in wall of cystic cavities)
• 25% are malignant (v aggressive growth, usually fills cavity, can perforate)

Question 12

Germ cell tumors

Answer 12

Germ cell tumors - 15-20%

1) Teratoma (can cause infertility)
a) Sometimes called dermoid cyst or benign cystic teratoma.
b) Derived from multipotential germ cells
c) Contains many mature tissue types – Sweat glands, hair, various epithelia, muscle, bone, cartilage, brain, and sometimes even teeth!

2) Choriocarcinoma

Question 13

GESTATIONAL TROPHOBLASTIC TUMORS

Answer 13

HYDATIDIFORM MOLE

CHORIOCARCINOMA

Question 14

HYDATIDIFORM MOLE (Definition, Epidemiology)

Answer 14

a. Defined as abnormal fertilization causing failure of the embryo to develop and proliferation of hydropic chorionic villi.
Benign tumor related to placenta, creates abnormal chorionic villi. Resembles a bunch of grapes

b. Epidemiology
1) Incidence – 1-1.5:2,000 pregnancies
2) Age predilection – under 20-years-old or over 40-years-old

Question 15

CHORIOCARCINOMA (Origin, Epidemiology)

Answer 15

a. This malignant uterine neoplasm is derived from TROPHOBLASTIC CELLS
Testes, uterus, ovaries (histo identical in all 3), invasive, aggressive behavior

b. Epidemiology
1) Incidence – occurs in 1 of 30,000 pregnancies in U.S.
2) Is more common in Asia and Africa, with incidence up to 1 in 2,000 pregnancies.
3) Predisposing Factors
a) 50% follow hydatidiform moles.
b) 25% arise after abortion.

Question 16

STDs in Males and Females (Nongonococcal urethritis/cervicitis)

Answer 16

A. Nongonococcal urethritis (M) and cervicitis (F) are the most common clinical pattern of STDs.
1. Most are caused by Chlamydia trachomatis.
2. Other important agents are Trichomonas vaginalis, Ureaplasma urealyticum, and Mycoplasma hominis.
T. vaginalis > big problem for women
U. urealyticum + M hominis > more common in men
Nongonococcal urethritis is always STD in men. Women may have it, but not STD.
Nongonococcal cervicitis can be asymptomatic
Drip/exudate = infection!

Question 17

Nodular Hyperplasia of Prostate (NHP = BPH) (S/S, Complications, Tx)

Answer 17

4. Clinical signs and symptoms
   a. Only 10% are symptomatic.
   b. Lower urinary tract obstruction
   1) Hesitancy – difficulty starting urination
   2) Intermittent interruption of urination
   3) Difficulty voiding bladder
5. Complications – related to obstruction
   a. Increased risk of urinary tract infections
   b. Hydronephrosis
   NOT precursor to prostate cancer!
6. Treatment
   a. TURP – transurethral prostatectomy
   b. Prevention – saw palmetto, progesterone will inhibit 5α-reductase.

Question 18

Carcinoma of the prostate (Morph, S/S)

Answer 18

3. Morphology
   a. Sites – peripheral zones
   Particularly posterior zone of prostate

b. Histology – adenocarcinoma
Cancer of GLANDULAR PORTION! NOT Sm. muscle.

4. Clinical Signs and Symptoms
   a. Usually asymptomatic until late stage. Symptoms occur due to metastatic disease.
   b. Can be found earlier by clinical examination – digital palpation via the rectum.
   c. Can screen for disease using PSA test.
   d. 20% are found in TURP specimen for NHP.
   e. May be initially found at autopsy.

Question 19

Testicular neoplasms (risk factors)

Answer 19

4. Risk Factors
   a. Cryptorchidism is seen in 10% men with testicular cancer. Cryptorchidism is defined as failure of the testis to descend into the scrotum by one year of age.
   Trapped in inguinal canal during 1st yr. Should be surgically tx’d or increase risk
   b. Klinefelter syndrome or testicular feminization
   Cytogenetically men, phenotypically women
   c. First degree relative with testicular cancer
   d. Cancer in contralateral testis

Question 20

Testicular neoplasms (Morphology)

Answer 20

5. MORPHOLOGY
   a. 60% are mixed histologic patterns.
   1) Most commonly are a combination of teratoma and embryonal carcinoma.
   2) May also contain yolk sac tumor and/or seminoma.
   b. 40% are single histologic type.
   1) 50% are seminoma – excellent prognosis
   2) 2-3% are embryonal carcinoma – poorer prognosis
   3) Yolk sack tumor is the most common testicular tumor in boys under 3 years old.
   4) Yolk sack tumors occur in adults only in mixed tumors.
   Benign teratoma > women, young boys
   Malignant > men
   5) Other Less Common Morphology Types
   a) Choriocarcinoma – poorer prognosis
   b) Immature teratoma – poorer prognosis

Question 21

SCC of uterine CERVIX (site, tx, prognosis)

Answer 21

c. Site – occurs usually at endocervix, arising in site of squamous metaplasia.

d. Treatment
1) Depends on stage
2) Early lesions can be removed by cone biopsy.
Removal of endometrium, may still have children
3) Larger lesions require hysterectomy.
4) May need to remove local lymph nodes.
5) Adjunctive therapy may also be used.

e. Prognosis – depends on stage

Question 22

Leiomyomas (Fibroids) of the UTERINE BODY (S/S, Tx)

Answer 22

4. Clinical signs and symptoms – depend on size and location
   a. Abnormal bleeding and pelvic pain are common.
   b. May cause infertility or spontaneous abortion.
   c. Also, may cause difficulty during labor and delivery

Tx: surgical removal

Question 23

Endometrial hyperplasia (S/S, Tx, Prognosis)

Answer 23

3. Clinical Signs and Symptoms
   a. May have either no symptoms or abnormal bleeding.
4. Treatment
   a. D and C = dilation and curettage
   Surgical removal
   b. Progestins/progesterone may help by balancing out hyperestrinism.
5. Prognosis – may progress to endometrial carcinoma.
   Precursor lesion for endometrial carcinoma when atypia is present

Question 24

ENDOMETRIAL CARCINOMA (Etiology, S/S, Tx, Prognosis)

Answer 24

3. Etiology
   a. Linked to hormonal imbalance
   b. Relative hyperestrinism, unopposed estrogen
   c. Often linked to post-menopausal estrogen therapy
4. Clinical signs and symptoms – abnormal uterine bleeding
5. Treatment
   a. Hysterectomy
   Usually curative, most common tx
   b. Radiation therapy
   c. Hormonal therapy – progestins/progesterone
6. Prognosis
   a. 5-year survival for stage 1 is 90%.
   b. 5-year survival for stage 3 or 4 is 20%.
   Stage 2 = 30-50%

Question 25

Surface germinal epithelium tumors (MUCINOUS TUMORS)

Answer 25

Surface germinal epithelium tumors = 65-70%
(90% malignant)

2) MUCINOUS TUMORS (filled with thick mucous)
a) Represent only 10% of ovarian tumors.
b) Occur in the same age as serous tumors – thirty something.
c) Mucinous tumors also exhibit a wide range of behavior.
• 80% are benign.
• 10% are borderline.
• 10% are malignant.

Question 26

HYDATIDIFORM MOLE (Types)

Answer 26

c. Types

1) “Complete” Mole
a) Empty egg is fertilized by 2 spermatozoa producing a diploid karyotype.
2 paternal haploid sets
b) Contains NO FETAL PARTS as this karyotype does not permit embryogenesis.
c) Formed entirely of miniature grape-like hydropic chorionic villi.

2) “Partial” Mole
a) Normal egg is fertilized by 2 spermatozoa producing a triploid karyotype.
2 paternal, 1 maternal
b) Karyotype permits early embryogenesis.
c) Will have some FETAL PARTS and some normal chorionic villi, in addition to the hydropic chorionic villi.

Question 27

HYDATIDIFORM MOLE (S/S, Tx, clinical significance)

Answer 27

d. Clinical Signs and Symptoms – usually present clinically with painless vaginal bleeding 16 to 17 weeks after conception.
Will cause + pregnancy test!

e. Treatment – dilation and curettage

f. Clinical Significance
1) 80% of complete moles are benign, but still increase risk of invasive hydatidiform mole.
2) 10% become invasive moles.
3) All hydatidiform moles increase the risk of choriocarcinoma.
4) 4% of hydatidiform moles are followed by choriocarcinoma.
Can be invasive!

Question 28

CHORIOCARCINOMA (S/S, Tx, prognosis)

Answer 28

c. Clinical Signs and Symptoms
1) Discovered by appearance of a bloody-brownish discharge
2) May have wide hematogenous dissemination (metastasis).

d. Treatment and Prognosis – nearly 100% of cases can be cured with chemotherapy.

Question 29

STDs: vs Venereal disease

Answer 29

1. Venereal disease is an STD involving the genital tracts, where genital tract is the usual target organ system.
2. Historical major venereal diseases are gonorrhea and syphilis.
3. Some organisms are now transmitted as STDs than once were only spread other ways.

C. Epidemiology

1. Chlamydia – More common now, higher in women, subclinical (don’t realize they are infected)
2. Gonorrhea – 60s, down after 80s
3. Syphilis – pre/during WWII. Chankres, self limiting, can recur. Tertiary stage, targets heart + brain (nervous system)