Female and Male Genital Tract Flashcards
What does the female genital tract consist of
vulva, vagina, uterus (cervix and body), fallopian tubes and ovaries
What does the male genital tract consist of
penis, scrotum, testis, epididymis and prostate
What cells line the exocervix vs. endocervical canal
The exocervix has a squamous cell lining, while the endocervical canal is lined by columnar mucin-secreting cells
What is the T-zone? When is it especially active?
The area of transition between the endocervix and the exocervix is the transformation zone (“T zone”). It is especially active after menarche and during pregnancy.
What happens in the T-zone and what is it due to?
the mucosa undergoes metaplastic transformation from columnar to squamous cells as a physiological response to the acid pH of the vagina
Why is the T-zone important
The immature metaplastic squamous cells are susceptible to mutagenic oncogenic stimuli, and are easily infected by human papilloma virus (HPV)
What are virtually all cases of cervical cancer proceeded by? What is this known as?
pre-cancerous changes in the cervical epithelial cells known as cervical dysplasia
In terms of cervical dysplasia, what has resulted in dramatically reduced incidence of invasive cancer of the cervix
Identification of the precancerous changes (by
“Pap” smears), clinical investigation (by colposcopy) and treatment (usually with laser)
Three terminologies and grading schemes in use today to report cervical dysplasia
- Squamous dysplasia (mild, moderate, severe)
- Cervical intraepithelial neoplasia (CIN Grade I, II and III)
- Squamous intraepithelial lesion (SIL), low-grade and high-grade – this is the preferred terminology
What are most cases of cervical dysplasia a result of?
infection by human papillomavirus
What is the single most important factor in the development of cervical dysplasia
HPV infection
Most cases of cervical dysplasia and cervical cancer are the result of which disease? Due to this, how can they be prevented?
Sexually transmitted diseases
- safe sex practices, i.e. condom use
- routine cytologic screening using the Papanicolaou test (“Pap smear”)
- HPV vaccination
What is HPV on a molecular scale?
a DNA virus which replicates in the nucleus, and has a predilection for squamous epithelium
What HPV virus causes genital warts? What is the scientific term for genital warts?
HPV 6 and 11, condyloma acuminatum
__% - __% of patients with genital warts have associated HPV infection of the vagina/cervix.
30 - 50
Which HPV subtypes promote precancerous changes? What may happened if left untreated?
HPV 16, 18, 31, 33, 35, may progress to cancer over a number of years
Risk factors for HPV
- young age at first intercourse
- multiple sexual partners
- smoking
- oral contraceptive use
- pregnancy
- diabetes
- immunosuppression
- poor hygiene
What has greatly reduced the mortality from cervical cancer
Since cervical dysplasia occurs mostly in the T-zone, sampling of this region with early detection
a simple, inexpensive, and generally reliable way to detect cervical dysplasia / SIL which is not visible to
the naked eye
PAP smear
At what age should women who have had sex get a regular Pap smear until?
69 ???
Explain the process of a pap smear and what happens when it is abnormal
A sample of cervical cells is obtained by gently scraping the T-zone with a small spatula or
brush. They are spread on a glass slide, sprayed with fixative, and sent to a cytology laboratory. After staining, dysplastic cells and HPV-containing cells (koilocytes) can be identified under the microscope. Women with mildly abnormal Pap smears are treated conservatively by having the Pap test repeated in 6 months since many low grade lesions spontaneously regress. If the Pap smears are consistently abnormal, glandular lesion or high grade SIL is detected, the patient is investigated by colposcopy - a technique for direct examination of the cervix under magnification - and biopsy confirmation. Treatment options include laser ablation or ‘cone’ excision of the transformation zone
__% of cervical cancers are squamous cell carcinomas.
90%
Symptoms of patients who present with invasive cancer of the cervix?
abnormal vaginal bleeding, especially post-coital spotting
Patients at risk for developing cancer of the cervix are the same as for cervical dysplasia. What co-factor also play a role?
immunodeficiency (HIV+ve and transplant patients)
Where do cervical cancers invade and where do they metastasize?
invade locally into the vagina, the rectum, and the bladder and metastasize to regional lymph nodes
What happens if cervical cancer entraps the ureters?
Leads to uremia and death
What are treatment options of cervical cancer?
Early invasive cases can be locally excised (cone
excisions), or treated with radical surgery (hysterectomy - removal of the uterus, cervix, and paracervical connective tissues)
More advanced cases are treated with radiotherapy
Survival rate of low grade cervical cancer vs advanced
low stage is excellent (around 90%); advanced disease (e.g. Stage IV) less than 20%
What two layers make up the uterus?
thick outer muscular layer (myometrium) and an inner cavity lined by endometrium
What does the endometrium consist of?
glands in a background of spindled stromal cells and blood vessels
What two hormones cause the endometrium to
undergo cyclical monthly changes? Where/how are they released?
estrogen and progesterone produced by the ovary, which in turn is regulated by hormones produced by the hypothalamus and pituitary
How does estrogen and progesterone effect the endometrium?
Estrogen stimulates the endometrial glands to proliferate. Once ovulation occurs, estrogen production subsides and progesterone production increases. The change in hormones causes the endometrium to convert from a “proliferative phase” to a “secretory phase”, in preparation to receive and nourish a fertilized egg. If implantation does not occur,
the endometrial lining is shed during the menstrual phase, and the process starts over again
What does the menstrual cycle rely on? When do problems occur?
relies on a precisely regulated sequence of events. Problems occur when the cycle becomes unbalanced and ovulation doesn’t occur or becomes sporadic
At what stage in a woman’s life do problems with the menstrual cycle most often occur?
Menopause
How can menopause turn into cancer?
Estrogen production stimulates the endometrium to proliferate, unopposed by progesterone. This results in
endometrial hyperplasia, and can ultimately result in endometrial carcinoma. Endometrial biopsy is required for diagnosis
What may unopposed estrogen be associated with?
- Failure to ovulate
-Perimenopausal failure to ovulate - ovary produces estrogen but no
progesterone.
-Polycystic ovarian disorder - young women who fail to ovulate due to disturbances in the hormonal control of ovulation - results in multiple dilated follicles (hence the
name ‘polycystic’ ovaries). - Hormone replacement therapy for control of menopausal symptoms - progesterone as well as estrogen should be prescribed.
- Obesity - increased amounts of estrogen are produced by fat cells (through conversion of androgens).
- Functional tumors - there are rare ovarian tumors that produce estrogens.
What is the typical sequence for the unopposed estrogen state?
- disorderly proliferation;
- non-atypical hyperplasia with simple or complex architecture;
- atypical hyperplasia;
- carcinoma
Non-atypical hyperplasia of the uterus vs. atypical (consequences and treatments)
non-atypical hyperplasia has a low risk of developing cancer (<5%) and may be treated with hormone therapy. If atypical hyperplasia is detected, there is a high risk of progression to cancer (25%) and hysterectomy is recommended at that point
What is the most common malignancy of the female genital tract and at what stage of life is it most common?
Endometrial adenocarcinoma, post-menopausally
__% of endometrial carcinomas are associated with unopposed estrogen stimulation
85%
Describe endometrial carcinoma tumors that are associated with unopposed estrogen
well-differentiated, low stage at presentation, and
generally have an excellent prognosis
Describe the remaining 15% of endometrial cancer that develop independent of estrogen
aggressive, invade deep into the myometrium,
are more likely to metastasize, and have a worse prognosis
What is the most common symptom of endometrial cancer
post-menopausal vaginal bleeding
When does endometriosis occur? How common is it?
when benign endometrial tissue is present outside the normal location in the uterus. Very common condition (up to 10% of female population).
What are the most common sites for endometriosis to occur?
ovaries, fallopian tubes, peritoneum and bowel
How does endometriosis occur and what forms can it be in?
endometrial tissue undergoes the same cyclic menstrual changes that affect the regular endometrium, but with no place to go, the blood and sloughed epithelium can expand into hemorrhagic cysts. Endometriosis may be in the form of tiny nodules, large fibrous masses, or hemorrhagic cysts
Typical symptoms of endometriosis
Pelvic pain, dysmenorrhea and infertility
Theories of the cause of endometriosis
- The regurgitation theory or retrograde menstruation through the tube, with implantation of endometrial tissue.
- Metaplasic transformation in the peritoneum and connective tissue - endometrial differentiation of coelomic epithelium (mesothelium of pelvis and abdomen from which endometrium originates) as the source.
- Vascular or lymphatic dissemination of endometrial tissue - “benign metastases”.
- Genetic predisposition; and more recently
- The extrauterine stem/progenitor cell theory, proposes that circulating stem/progenitor cells from the bone marrow differentiate into endometrial tissue.
Potential sites of endometriosis
The ovaries are most frequently involved (80%), but other areas and pelvic organs may be affected as well
What are the most common tumors of the female genital tract? What are they composed of and where are they situated?
leiomyomas are benign neoplasms composed of smooth muscle, usually situated within the myometrium
What are leiomyomas more commonly known as
fibroids
Fibroids are found in __ - __ % of women over the age of 30 yr, and are present in __% of hysterectomy specimens.
30 - 50, 75
What receptors do the smooth muscle cells which
make up a leiomyoma express?
Estrogen and progesterone
Growth of leiomyoma’s is affect by what?
hormonal alterations:
Decreased size after menopause
Increased size with pregnancy
Gross appearance of leiomyomas
round or spherical
well-circumscribed
rubbery, white-tan-grey
have a whorled cut surface
often multiple;
variable size - less than 1 cm to over 20 cm;
location - intramural, submucosal, subserosal;
may be pedunculated and hang from a stalk.
Symptoms of leiomyoma
- may be asymptomatic
- or present with
o bleeding;
o pelvic pain;
o dysmenorrhoea (painful menstruation);
o infertility
How many pregnancies implant in areas other than the endometrial cavity
1 in 150
What increases the risk of ectopic pregnancy
Any disease that results in scarring or distortion of the
tubes (e.g. infection or endometriosis or adhesions)
What happens following the implantation of a fertilized ovum?
the chorionic villi of the developing placenta invade the wall of the tube. As the embryo grows, the fallopian tube expands, and there may be rupture with massive intraperitoneal hemorrhage and shock
What is a a generic term used for an infectious and inflammatory disorder of the upper female reproductive tract
Pelvic Inflammatory Disease (PID)
What is salpingitis?
Infection of the tube
PID is usually an _______ infection
Ascending
PID may occur from…
sexually transmitted, follow an abortion or pregnancy, or occur after an IUD insertion or a curettage
The main microorganisms of PID
chlamydia and neisseria gonorrheae; mycobacterium (genital tract tuberculosis) is rare in Canada, but very important world-wide
PID - Inflammation of the endometrium is typically mild and the brunt of the infection is on the tube. What happens to the tube and what is the name for this?
The delicate tubal plicae are destroyed and the fimbrial end closes off resulting in a distended tube filled with pus (pyosalpinx)
How is a tubo-ovarian abscess formed
The inflammatory reaction in the tube involves the peritoneum and may also involve the ovary to form a tubo-ovarian abscess.
Sequelae of PID
- chronic salpingitis - fibrosis, chronic inflammation, and complaints of chronic pelvic pain,
- hydrosalpinx - a thin distended tube filled with clear fluid,
- tubo-ovarian abscess
- dense adhesions,
- infertility,
- ectopic pregnancy
What does the normal ovary consist of? What can each cell type do?
• Surface epithelium (and epithelial inclusions)
•Germ cells
-Egg production
• Stroma and sex cord cells (e.g. granulosa and theca cells, leydig cells etc.)
-Support the germ cells
-Produce hormones
–> can give rise to tumors that have benign and malignant counterparts
Why are epithelial cells of the ovary complicated?
some tumors in the epithelial group fall into a borderline category, which are atypical and locally proliferative, but not frankly malignant
Typical presentation of benign epithelial ovarian tumor. What is the most frewuent cause?
a cystic ovarian mass in a young woman (functional or physiological cyst). In a young woman, the most frequent cause of an ovarian mass is a cyst derived from a ripening follicle (follicle cyst) or a corpus luteum (luteal cyst). These disappear spontaneously over 4-6 weeks.
◦Often multicystic. May be massive.
◦Lack significant solid growth of tumor cells
◦Lack invasion by definition
What is the leading cause of death from gynecologic malignancy
Ovarian carcinoma
Why does ovarian carcinoma tend to have a worse outcome
Often asymptomatic, or mild non-specific symptoms until late
No specific screening test
Therefore more likely to present at an advanced stage
Typical presentation of ovarian carcinoma
an ovarian mass in a post-menopausal woman, tumor is frequently bilateral, usually mixed cystic and solid, often with papillary growth. Neoplastic cells have the ability to invade, and potential to metastasize
Patterns of spread of ovarian carcinoma
o Opposite ovary o Adjacent structures (bowel, bladder etc.) o Lymph nodes o Peritoneum o Distant sites (liver, lung)
What is mature cystic teratoma
neoplasm derived from germ cells of the ovary
What germ layers of the ovary have the capacity to differentiate
All of them
ectoderm (skin and skin appendages such as hair and sweat (sebaceous) glands);
endoderm (respiratory and intestinal epithelium);
mesoderm (cartilage, bone, fat).
What is considered a dermoid cyst?
When skin, hair and other skin appendages predominate
What are the most common ovarian neoplasm in young women?
Mature cystic teratomas
Mature cystic teratomas are entirely benign as long as….
as all of the tissues are mature
explain immature teratomas
Primitive tissue in addition to mature elements, usually embryonic neural tissue
Tumor grade and malignant potential depends on amount of immature tissue present
explain dysgerminoma
Most common of the malignant germ cell tumors
Female equivalent of a testicular seminoma, in both appearance and behavior
Where do Granulosa Cell Tumors originate and what effects do they normally have?
originates in the stroma of the ovary and it often has hormonal effects - can produce estrogen which can lead to endometrium hyperplasia or carcinoma
At what age do most granulosa cell tumors occur?
45-55
Where is a frequent place for Malignant tumors that arise in the gastrointestinal tract, breast, endometrium and elsewhere to metastasize
Ovary
Where does the prostate sit
at the base of the bladder
What are produced in the prostatic glands
Secretions
Prostatic secretions make up a sizable volume of what?
Ejaculation
What do prostate secretions help with?
Not neccessary for fertilization but optimize the conditions needed
How does the prostate help facilitate fertilization? (3)
May help close off bladder neck during sex
Provides support for the sperm cells
- Nutritional role for sperm cells
- Buffer the acidic environment of the vagina
- Enzyme (PSA) in prostate fluid breaks down proteins to liquefy the semen, allowing
sperm to migrate more freely
Has contractile properties to assist in ejaculation
Due to its location, what is the urethra susceptible to?
Because of the relationship of the proximal urethra to the prostate, the urethra is susceptible to compression from hyperplastic enlargement of the prostate
What are the anatomical zones of the prostate susceptible to?
the centrally located zones are prone to hyperplasia in older men, while the peripheral zone is much more frequently affected by carcinoma
What is the most common urologic disease of older men and what else can it cause?
Prostatic enlargement –> urinary obstruction
Terms for prostatic hyperplasia
BPH (benign prostatic hyperplasia), or nodular
hyperplasia
What does prostatic hyperplasia result in
nodular proliferation of glands and stroma, typically in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethra, causing partial or complete urinary obstruction.
Incidence of prostatic hyperplasia
Incidence rises rapidly after age 40 yrs.
Pathologic evidence of hyperplasia is present in 50% of men aged 50-60 yrs. This rises to 90% of men in their 80s. Note that not all of these patients will present with symptoms of obstruction
Complications of prostatic hyperplasia
- Urinary Tract Obstruction - symptoms:
o frequency, urgency, nocturia (waking up at night to void)
o decrease in the calibre and force of the urinary stream,
o hesitancy in initiating urination,
o a sensation of incomplete emptying of the bladder.
-Late complications - chronic obstruction:
o bladder hypertrophy
o dilatation / trabeculation of bladder wall
o urinary stone formation.
What is the most common form of malignancy in men
Prostatic adenocarcinoma
Typical age of prostatic adenocarcinoma
While rare before age 40 yrs, incidence rises rapidly in older men (1 in 7 chance of being diagnosed during lifetime; 1 in 27 chance of dying from prostate carcinoma).
Risk factors of prostatic adenocarcinoma
Genetic / racial factors
- Different rates in various parts of the world
- ->Most common in men of sub-Saharan African descent
- ->High in North America, Australia, northern and central Europe
- ->Least common in Asian populations
- Familial predisposition
- -> Increased risk and earlier age of presentation if strong family history
- -> Various specific gene mutations have been documented
Dietary factors
- Obesity and diet high in fats may increase risk
–> e.g. Asians who migrated to US have increased risk of prostate cancer
compared to native Asian population - Smoking
- -> Increased risk of mortality and disease recurrence in smokers
% of prostatic adenocarcinoma cases that are asymptomatic
50%
Gleason grading for prostatic adenocarcinoma
Grade = how ugly the tumor looks under microscope
Based on extent of gland formation. Higher the grade, more solid growth / less gland
formation
Low grade tumors have a more indolent course; high grade tumors more likely to
metastasize
Where does the prostate commonly metastasize to
lymph nodes, bones
Why do more patients die with prostate cancer than from prostate cancer?
Prostate cancer relatively slow growing, and slow to spread
