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
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
o
o
o
o
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
o
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
o
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
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)
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
o
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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
o
o
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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
o
o
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
o
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
o
o
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
o
o
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
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
Vulvar intraepithelial neoplasia (VIN)—some increased risk
for vulvar cancer in women with VIN
Other genital cancers
Smoking
Diabetes