Female Genital Tract Flashcards
Endometrium
The endometrium of the uterus consists of glands and stroma which makes up the innermost lining of the uterus.
Estrogen:
- Causes Gland proliferation
Ovulation:
- occurs when ↑ progesterone → convert to secretory
If ovulation impaired”
- Estrogenic growth stimulus continues
- “Unopposed” by progesterone
Consequences:
- Dysfunctional bleeding
- Endometrial hyperplasia
- Possible progression to carcinoma
Causes of unopposed estrogen
Failure to ovulate:
- Older age
- Hormonal imbalances (e.g. polycystic ovary disorder)
Obesity:
- Fat cells convert androgens to estrogens
Medication:
- Estrogen replacement therapy without balancing progesterone
- Tamoxifen for breast cancer
ENDOMETRIAL HYPERPLASIA
An excess of estrogen relative to progestin, if sufficiently prolonged or marked can induce exaggerated endometrial proliferation hyperplasia which is an important precursor of endometrial carcinoma.
Proliferating Endometrium - we begin to more glands but also more dilated glands.
ENDOMETRIAL ADENOCARCINOMA
Most common malignancy of female genital tract
Usually postmenopausal
~85% associated with hyperestrinism
Cases not associated with estrogen more aggressive
LEIOMYOMA (“FIBROID”)
Benign tumors that arise from the smooth muscle cells in the myometrium are properly termed leiomyomas but because of their firmness often are referred to clinically as fibroids.
- Benign tumor of smooth muscle
- Very common
— 25% of women over 30 years
Symptoms
- Depend on size, location, and number
- Pain, bleeding, infertility
- May be asymptomatic
Types of Fibroids
Intramural
Submucosal
Subserosal
Endometriosis
Endometriosis is defined by the presence of endometrial glands and stroma in a location outside the uterus.
- Ectopic endometrial tissue
- Very common (10% of women)
- Estrogen dependent
Symptoms:
- Pelvic pain, often cyclical
- May be severe: nausea, insomnia, fatigue, depression
- Infertility
Endometriosis Etiology
Theories based on:
Deposition of endometrial (stem?) cells
- Retrograde menstruation?
- Circulating stem cells?
- Metaplastic transformation?
Survival and growth of seeded tissue
- Alterations in the biology of the ectopic tissue
- Host inflammatory response
- Genetic, epigenetic, and environmental influences
INFECTION (PELVIC INFLAMMATORY DISEASE)
Complications
- Pelvic pain
- Abscess
- Infertility
- Adhesions
- Ectopic pregnancy
- Hydrosalpinx (dilated fallopian tube)
ECTOPIC PREGNACY
Ectopic pregnancy is defined as the implantation of the fertilized ovum outside of the uterine corpus. Approximately 1% of pregnancies implant ectopically; the most common site is the fallopian tube.
Hydrosalpinx (dialted fallopian tube)
Dilated, thin walled Fallopian tube
Ovarian neoplasia
Epithelial
- 65-70% of cases
- Adults
- Majority benign
- Cancer in older
Germ cell
- 15-20% of cases
- Young (<25 yr)
- Similarities with testicular tumors
Benign Epithelial Ovarian Neoplasm
Lots of cysts that are thin walled - looks like soap bubbles
Cysts are lined by mucinous cystadenoma
Ovarian cancer
Many kinds of “ovarian cancer” (epithelial, germ cell, sex cord)
High grade serous carcinoma most common (epithelial differentiation)
Leading cause of death from gyn malignancy (>cervix or endometrium)
Often asymptomatic, or non-specific until late stage
No specific screening test
More likely to present at an advanced stage
Ovarian cancer - risk factors and protective factors
Risk factors
- Age
— (↑ post-menopausal)
- Genetics
— Personal history breast cancer
— Family history ovary & breast / colon cancer (BRCA / Lynch)
- Hormonal
— No children / late first pregnancy
— Estrogen therapy (w/o progestin)
- Endometriosis
Protective factors
- Progesterone effects:
— Early age of 1st pregnancy
— Breastfeeding
— Oral contraceptives
— Progesterone infused IUD
TUBAL VS OVARIAN ORIGIN OF OVARIAN CARCINOMAS
Tubal Origin (High grade serous carcinoma)
- Most common so-called “ovarian” cancer
- Tubal origin for HGSC a new concept
- Pre-cancerous changes in tube
- Strong p53 link; BRCA link in some
Ovarian Origin (Endometrioid, clear cell, mucinous, LG serous)
- Pre-cancerous changes in ovary
- From endometriosis or epithelial inclusions
- Often less aggressive than HGSC
- Different genetic mutations than HGSC
OVARIAN CARCINOMAS - Outcome
Only 1/3 of cases confined to ovary
Surgery ± chemotherapy
5-year survival:
I: Confined to ovary – 90%
II: Pelvic spread – 70%
III: Lymph node or abdominal spread – 40%
IV: Distant metastasis – <20%
VULVAR DISEASES
Non-neoplastic
- Infections (e.g. HPV)
- Various dermatologic conditions
Neoplastic
- Pre-cancerous changes
- Squamous cell carcinoma
- Other neoplasms (much less common)
HUMAN PAPILLOMA VIRUS (HPV)
STI which infects squamous cells
Multiple HPV subtypes:
- Low risk strains (e.g. 6, 11):
— Condyloma (warts)
High risk strains (e.g.16, 18):
- Pre-cancerous changes
Risk Factors - HUMAN PAPILLOMA VIRUS (HPV)
Behavioral based
- Young age of first intercourse
- Multiple sexual partners
- Unprotected intercourse
- Smoking
Biological based
- Host factors
— Immune response, etc.
- Viral factors
— HPV type, viral load, etc.
- Weakened immune system
VULVAR CONDYLOMA ACCUMINATUM
Genital warts
HPV-6 and HPV-11
Usually multiple
Recurrence common
30-50% associated cervical infection
VULVAR INTRAEPITHELIAL NEOPLASIA (VIN)
- Mostly squamous cell carcinoma
- Preceded by pre-cancerous changes
HPV associated (high risk viral strains)
- Younger age
- Multifocal disease
- Recurrent
Non-HPV (p53 mutation)
- Older age
- Solitary lesions
- Linked to chronic inflammatory lesions
- Higher risk of progression to invasion
SQUAMOUS CELL CARCINOMA
There appear to be two distinct forms of vulvar squamous cell carcinomas that differ in pathogenesis and course.
- The less common form is related to high-risk HPV strains and occurs in middle-aged women, particularly cigarette smokers. This form is often preceded by precancerous changes in the epithelium termed vulvar intraepithelial neoplasia (VIN).
- A second form of squamous carcinoma occurs in older women, sometimes following a long history of reactive epithelial changes, principally lichen sclerosus. It is preceded by a subtle lesion, differentiated vulvar intraepithelial neoplasia (dVIN). If left untreated it may give rise to HPV negative, well-differentiated, keratinizing squamous cell carcinoma.
CERVIX
The cervix is a cylinder-shaped neck of tissue that connects the vagina and uterus. Located at the lowermost portion of the uterus, the cervix also is the site of one of the most common cancers in women worldwide
Transformation zone
- During development, the columnar mucus-secreting epithelium of the endocervix is joined to the squamous epithelial covering of the exocervix at the cervical os.
- During puberty, some columnar epithelium become visible on the exocervix and these exposed columnar cells, eventually undergo squamous metaplasia, forming a region called the transformation zone, where tumours most commonly arise.
