Transcript File

Benign & Malignant Diseases of the
Female Genital Tract
Jennifer McDonald DO F.A.C.O.G
February 22, 2008
When to Suspect Gynecologic Cancer
 Premenopausal
woman with:
Irregular menses
Women older than 35 or with long history of
irregular menses
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
 Postmenopausal
Vaginal bleeding
Abnormal vaginal discharge


woman with:
Gynecologic Malignancies 2005
Breast
o Uterus (womb)
o Ovary
o Cervix
o Vulva
o
211,240
40,880
22,200
10,400
3,870
Criteria for Screening Test
1. Simple & quick
2. Inexpensive
3. Acceptable to population
4. Accurate
5. Repeatable
6. Sensitive
7. Specific
Screening Tests that Impact Lives
Mammography
o Pap Smears
o Diabetes screening
o Colonoscopy
o Thyroid screening
Prostate specific antigen
o
o
The Uterus
Leiomyoma
Also known as fibroids
Local proliferation of smooth muscle cells of
the uterus
o Benign tumors
o 20-25% of reproductive aged women
o 3-9x more frequent in African American
women
o Half to one third of hysterectomies
performed
o
o
Leiomyoma
o
Majority are asymptomatic (50-65%)
o When symptomatic can cause:
Metrorrhagia
• Menorrhagia
• Pain
• Infertility
•
Cause unknown
Hormonally responsive
o Commonly multiple
o
o
Classified according to location
Indications for Surgical Intervention
o
Abnormal uterine bleeding causing anemia
o Severe pelvic pain
o Urinary frequency or retention
o Growth after menopause
o Infertility
o Rapid increase in size
Endometriosis
Endometrial glands/stroma outside the
endometrial cavity
o Most common sites: pelvic peritoneum,
posterior cul-de-sac, round ligament,
uterosacral ligaments
Incidence 10-15% reproductive age women
o 20% of women with chronic pelvic pain
o 40% of women with infertility
o
o
Etiology
Theories
o
Halban: endometrial tissue transported via lymphatic
system to ectopic sites in the pelvis
o
Meyer: multipotential cells in peritoneal cells
undergo metaplastic transformation into functional
endometrial tissue
o
Sampson: endometrial tissue transported through
the tubes during retrograde menstruation
Clinical Manifestations
Dysmenorrhea
o Dyspaurenia
o Infertility
o Abnormal bleeding
o Cyclic pelvic pain
o
o
Severity of symptoms does not correlate with
amount of endometriosis
The Faces of Endometriosis
Adenomyosis
o
Extension of endometrial glands/stroma into
the uterine musculature
o Causes diffuse enlargement of the uterus
o Incidence 15%
o 15% patients with adenomyosis have
endometriosis and 50-60% have fibroids
o Most common symptoms: secondary
dysmenorrhea (30%), menorrhagia (50%) or
both (20%)
o 30% are asymptomatic
Endometrial Cancer
Most common gynecologic cancer
o Early symptoms and accurate diagnostic
modalities make it the 3rd leading cause of
gyn cancer deaths
o Estrogen dependent neoplasm
o Mean age 61 years
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o
o
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25% premenopausal
75% postmenopausal
75% at Stage I at diagnosis
o 75% adenocarcinomas
Risk Factors for Endometrial Cancer
Early menarche
(<age 12)
o Late menopause
(>age 52)
o Infertility or nulliparous
o Obesity (>30# overweight)
o Treatment with tamoxifen
for breast cancer
o Estrogen replacement
therapy (ERT) after
menopause
o Diet high in animal fat
Diabetes
o Age greater than 40
o Caucasian women
o Family history of
endometrial cancer or
hereditary nonpolyposis
colon cancer (HNPCC)
Personal history of breast or
ovarian cancer
Prior radiation therapy for
pelvic cancer
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o
o
o
Endometrial Cancer
Most common symptom is
irregular bleeding (90%)
o No effective screening test
o Endometrial biopsy standard of
care
o May require D&C
o Surgery is first choice for
therapy
o Overall 5 year survival rate 65%
with 85% recurrences within first
3 years
o
Ovary
Dermoid Cyst
o
o
Ovarian cyst containing
hair, teeth, cartilage
Stem cells that “forgot”
to migrate
Radiologic Differences
Benign
Simple cysts < 10 cm
o Septations < 1mm
thickness
o Unilateral
Calcifications esp teeth
o Gravity dependent
layering of cyst
contents
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o
Malignant
o
o
Solid or cystic & solid
Multiple Septations >
3mm size
o Bilateral
o Ascites
Ovarian Cancer
o
Worldwide the incidence of ovarian cancer
is 12.7/100,000 at all ages
o In USA the incidence is 10.2 /100,000
before 65 years and is 57.1/100,000 at or
above 65 years
o Only 30% survive for 5 years after
diagnosis
75% Patients have disease beyond the ovary at time
of diagnosis (Stage III or higher)
Ovarian Cancer
o
o
o
o
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
2nd
25,000 new cases/yr
most common GYN cancer
Usually NOT due to a predisposing genetic factors
Only 5-10% of ovarian cancers are related to genetic
mutations
 BRCA1
 BRCA2
Increased risk in patients with hereditary nonpolyposis
colon cancer (HNPCC) mismatch repair gene mutations
Increased risk in patients with Peutz-Jeghers
syndrome STK11 tumor suppressor gene mutation
Risk Factors for Ovarian Cancer
Early menarche (< age 12)
 Late menopause (> age 52)
 Age (> 50)
 Later age of first pregnancy (> age 30)
 Infertility
 Personal history of breast or colon cancer
 Family history of ovarian, breast or colon
cancer

Oral contraceptives have been found to have a
protective effect for ovarian cancer
Symptoms

Lower abdominal discomfort
Bloated or fullness
 Loss of appetite
 Nausea, gas, indigestion
 Vaginal bleeding
 Weight loss
 Constipation or diarrhea
Frequent urination (due to pressure from
growing tumor on bladder)
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
o
Unfortunately symptoms do NOT normally present
until the cancer is at an advanced stage
Screening
o
Pelvic ultrasound has not been proven to be an
effective screening tool
Serum markers
CA-125: Secreted by 80% of epithelial ovarian cancers
o Sensitive but not specific
o Used to monitor progression and regression but no
value for screening purposes
Conditions Associated with Elevated CA-125
Malignancies
o Epithelial Ovarian
Cancer
o Fallopian Tube Cancer
o Endometrial Cancer
o Endocervical Cancer
o Pancreatic Cancer
o Lung Cancer
o Breast Cancer
o Colon Cancer
Benign Conditions
o Normal & ectopic
pregnancy
o Endometriosis
o Fibroids
o Pelvic Inflammatory
Disease
o Pancreatitis
o Peritonitis
o Cirrhosis
o Recent abdominal
surgery
Treatment
o
o
Surgery is preferred in almost all cases when
possible for debulking of tumor load
o Surgically staged: Total hysterectomy,
oomentectomy, and tumor debulking
o Epithelial ovarian cancers are highly
chemosensitive to cisplatin based combination
chemotherapy agents and Taxol
Radiation plays little role in the treatment of
ovarian cancers
Survival
Stage
Stage
Stage
Stage
I
II
III
IV
80-95%
40-70%
30%
< 10%
Germ Cell Tumors
15-20% Ovarian tumors
o Arise from totipotential germ cells
o 95% are benign
o Women in their teens and 20s
Rapidly enlarging adnexal mass and pain
Diagnosed earlier and treatment usually
limited to removal of affected ovary
o Highly curable with surgery and
chemotherapy
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Cervix
Cervical Cancer
o
The incidence of cervical cancer in USA is
7.2/100,000 under the age of 65 and
16.1/100,000 at or above 65 years
o Worldwide the incidence at all ages is
7.6/100,000
o The endocervix epithelium contains
receptors for sex hormones
Cervical Cancer Statistics
500,000 women worldwide die of cervical
cancer annually
o 50-60 million women in the U.S. have a Pap
test each year
o 3-5 million women in the U.S. have an abnormal
result
o 10,400 new cervical cancers diagnosed in the
U.S. per year
o 3,900 deaths from cervical cancer in the U.S.
per year
o
Risk Factors for Cervical Cancer
Cigarette smoking
o High number of sexual partners
o Early onset of sexual activity
History of sexually transmitted diseases
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In patients with HIV invasive cervical cancer
is considered an AIDS defining illness
Treatment
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Stage IA1/IA2 cone biopsy may be sufficient
o Surgery helpful in only Stage IIA or less
40% will be diagnosed at IB (85% cure rate)
Combination chemotherapy/radiation just as
good as surgery in IB disease
More advanced lesions treated with radiation
and platinum chemotherapy
Screening Tools - Pap Smear
Premalignant phase of
many years
o Inexpensive
o Readily accepted
o Easy to perform
o 50% of women who
receive cervical cancer
diagnosis never had a pap
smear
o 10% had not been
screened in 5 years
o
Timing of Screening
Three years after initiation of sexual
intercourse but no later than 21 years of age
Annual cytology screening for women younger
than 30
o Women 30 years and older who have had
three negative cytology tests in a row may be
screened every 2-3 years
Women with HIV, immunosuppression, or DES
exposure may require more frequent
screening
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Discontinuation of Screening
o
ACS recommends discontinuation at age 70 in
low risk women
o
Women with previous hysterectomy and no
history of high grade CIN may discontinue
screening
Cytologic Abnormalities
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Dysplasia thought to be precursor to cervical
cancer
On average takes 7 years for a CIN1 lesion to
progress to a cancer and 4 years for a CIN2
lesion
o 75-90% of CIN1 lesions will resolve
spontaneously
o 50% of CIN2 spontaneously resolve
o 30% of CIN3
ASCUS
Atypical Squamous Cells of Undetermined
Significance
May be anything from inflammatory process
to a neoplastic process
o Reflex HPV testing performed
o If positive for high risk types should proceed
with further testing
o If negative for high risk types may continue
yearly screening
o
Colposcopy
Done in follow-up to
abnormal smear
o Magnified view of cervix
o Surfaced stained with
acetic acid
o Biopsies taken to rule out
advanced disease
o
Low Grade/CIN1
o
o
Usually caused by transient HPV infection
o 75-90% regress
o Confirmed by coloposcopic biopsy
Repeat pap smears every 6 months until 3
normal smears in a row then may return to
yearly screening
HGSIL/CIN2-3
o
o
Less chance of regression than progression
Usually destructive procedures or excision
performed
Cryotherapy
o Laser therapy
LEEP (loop electrosurgical excision procedure)
o
o
Human Papillomavirus (HPV)
200 different subtypes
o More than 30 transmitted sexually
Primary causative agent of cervical cancer in over
95% of cases
o Predominantly types 16 and 18 (70%)
More than 75% sexually active women tested have
been exposed to HPV by age 18-22
Most people who have been exposed will display no
symptoms and will clear the infection on their own
o
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Gardasil
Quadrivalent HPV vaccine
Targets type 16,18 (cervical cancer) as well as
types 6 and 11 (genital warts)
o Released June 2006
o Approved for all women aged 9 to 26
o 3 doses ($120/dose)
o
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Vaccine Efficacy
Vaginal & Vulvar Cancer
Vaginal & Vulvar Cancer
The incidence of cancer of vagina and vulva
is low i.e 0.5 and 2/100,000 women
respectively
o These cancers are common at an advanced
age.
o No relevant information is known about any
connection between HRT and these cancers
o
Vulvar
Lesion(s) on surface of vulva or labia; malignancy most often on
labia majora or minora
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3,870 new cases and 870 deaths in the US in 2005
o
Rare disease 0.5% of all cancers in women
90% of vulvar cancers are squamous cell carcinomas
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Melanoma 2nd most common found in labia minora or clitoris
o Other types of vulvar cancer:
 Adenocarcinoma
 Paget's disease
 Sarcomas
 Verrucous carcinoma
 Basal cell carcinoma
Risk Factors
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Age: 3/4 patients >50; 2/3 >70
Chronic vulvar inflammation/irritation
Infection with the human papillomavirus (HPV)
Human immunodeficiency virus (HIV) infection
Lichen sclerosis
Melanoma or atypical moles on non-vulvar skin
 Family
history of melanoma and dysplastic nevi
anywhere on the body may increase risk of
vulvar cancer
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Vulvar intraepithelial neoplasia (VIN)—some increased risk
for vulvar cancer in women with VIN
Other genital cancers
Smoking
Diabetes