Benign & Malignant Diseases of the Female Genital Tract

Jennifer McDonald DO F.A.C.O.GFebruary 22, 2008

When to Suspect Gynecologic Cancer

Premenopausal woman with: Irregular menses

Women older than 35 or with long history of irregular menses

Postmenopausal woman with: Vaginal bleeding

Abnormal vaginal discharge

o Breast 211,240o Uterus (womb) 40,880o Ovary 22,200o Cervix 10,400o Vulva 3,870

Source: American Cancer Society.

Gynecologic Malignancies 2005

Criteria for Screening Test

11. Simple & quick. Simple & quick

22. Inexpensive. Inexpensive

33. Acceptable to population. Acceptable to population

4. 4. AccurateAccurate

5. 5. RepeatableRepeatable

6. Sensitive6. Sensitive

7. 7. SpecificSpecific

Screening Tests that Impact Lives

o Mammographyo Pap Smears

o Diabetes screeningo Colonoscopy

o Thyroid screeningo Prostate specific antigen

The Uterus

Leiomyomao Also known as fibroids

o Local proliferation of smooth muscle cells of the uterus

o Benign tumorso 20-25% of reproductive aged women

o 3-9x more frequent in African American women

o Half to one third of hysterectomies performed

Leiomyomao Majority are asymptomatic (50-65%)

o When symptomatic can cause:• Metrorrhagia• Menorrhagia

• Pain • Infertility

o Cause unknowno Hormonally responsive

o Commonly multiple

Classified according to location

Indications for Surgical Intervention

o Abnormal uterine bleeding causing anemiao Severe pelvic pain

o Urinary frequency or retentiono Growth after menopause

o Infertilityo Rapid increase in size

Endometriosiso Endometrial glands/stroma outside the

endometrial cavityo Most common sites: pelvic peritoneum,

posterior cul-de-sac, round ligament, uterosacral ligaments

o Incidence 10-15% reproductive age women

o 20% of women with chronic pelvic paino 40% of women with infertility

EtiologyTheories

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 tissueo Sampson: endometrial tissue transported

through the tubes during retrograde menstruation

Clinical Manifestationso Dysmenorrhea

o Dyspaureniao Infertility

o Abnormal bleedingo Cyclic pelvic pain

o Severity of symptoms does not correlate with amount of endometriosis

The Faces of Endometriosis

Adenomyosiso Extension of endometrial glands/stroma into

the uterine musculatureo Causes diffuse enlargement of the uterus

o Incidence 15%o 15% patients with adenomyosis have endometriosis and 50-60% have fibroidso Most common symptoms: secondary

dysmenorrhea (30%), menorrhagia (50%) or both (20%)

o 30% are asymptomatic

Endometrial Cancero Most common gynecologic cancer

o Early symptoms and accurate diagnostic modalities make it the 3rd leading cause of

gyn cancer deathso Estrogen dependent neoplasm

o Mean age 61 yearso 25% premenopausal

o 75% postmenopausal

o 75% at Stage I at diagnosiso 75% adenocarcinomas

Risk Factors for Endometrial Cancer

o Early menarche (<age 12)

o Late menopause (>age

52)o Infertility or nulliparous

o Obesity (>30# overweight)o Treatment with tamoxifen

for breast cancero Estrogen replacement

therapy (ERT) after menopause

o Diet high in animal fat

o Diabeteso Age greater than 40

o Caucasian womeno Family history of endometrial cancer or

hereditary nonpolyposis colon cancer (HNPCC)

o Personal history of breast or ovarian cancer

o Prior radiation therapy for pelvic cancer

Endometrial Cancero Most common symptom is

irregular bleeding (90%)o No effective screening test

o Endometrial biopsy standard of care

o May require D&Co Surgery is first choice for

therapyo Overall 5 year survival rate

65% with 85% recurrences within first 3 years

Ovary

Dermoid Cyst

o Ovarian cyst containing hair, teeth, cartilage

o Stem cells that “forgot” to migrate

Radiologic DifferencesBenign

o Simple cysts < 10 cmo Septations < 1mm

thicknesso Unilateral

o Calcifications esp teeth

o Gravity dependent layering of cyst

contents

Malignant

o Solid or cystic & solido Multiple Septations >

3mm sizeo Bilateralo 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 yearso Only 30% survive for 5 years after

diagnosis

75% Patients have disease beyond the ovary at time of diagnosis (Stage III or higher)

o 25,000 new cases/yro 2nd most common GYN cancer

o Usually NOT due to a predisposing genetic factors

o 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

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

Risk Factors for Ovarian Cancer

Oral contraceptives have been found to have a protective effect for ovarian cancer

Lower abdominal discomfortBloated or fullness

Loss of appetiteNausea, 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

Symptoms

Screeningo Pelvic ultrasound has not been proven to

be an effective screening tool

Serum markersCA-125: Secreted by 80% of epithelial ovarian

cancerso Sensitive but not specific

o Used to monitor progression and regression but no value for screening purposes

Conditions Associated with Elevated CA-125

Malignancieso Epithelial Ovarian

Cancero Fallopian Tube Cancer

o Endometrial Cancero Endocervical Cancer

o Pancreatic Cancero Lung Cancer

o Breast Cancero Colon Cancer

Benign Conditionso Normal & ectopic

pregnancyo Endometriosis

o Fibroidso Pelvic Inflammatory

Diseaseo Pancreatitiso Peritonitiso Cirrhosis

o Recent abdominal surgery

Treatmento Surgery is preferred in almost all cases when possible for debulking of tumor loado Surgically staged: Total hysterectomy,

oomentectomy, and tumor debulkingo Epithelial ovarian cancers are highly

chemosensitive to cisplatin based combination chemotherapy agents and

Taxolo Radiation plays little role in the treatment

of ovarian cancers

Survival

Stage I 80-95%Stage II 40-70%Stage III 30%Stage IV < 10%

Germ Cell Tumorso 15-20% Ovarian tumors

o Arise from totipotential germ cellso 95% are benign

o Women in their teens and 20so Rapidly enlarging adnexal mass and paino Diagnosed earlier and treatment usually

limited to removal of affected ovaryo Highly curable with surgery and

chemotherapy

Cervix

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 yearso Worldwide the incidence at all ages is

7.6/100,000o The endocervix epithelium contains

receptors for sex hormones

Cervical Cancer

o 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

Cervical Cancer Statistics

Risk Factors for Cervical Cancer

o Cigarette smokingo High number of sexual partners

o Early onset of sexual activityo History of sexually transmitted diseases

o In patients with HIV invasive cervical cancer is considered an AIDS defining

illness

Treatmento Stage IA1/IA2 cone biopsy may be sufficient

o Surgery helpful in only Stage IIA or less

o 40% will be diagnosed at IB (85% cure rate)o Combination chemotherapy/radiation just as

good as surgery in IB disease

o More advanced lesions treated with radiation and platinum chemotherapy

Screening Tools - Pap Smearo Premalignant phase of

many yearso Inexpensive

o Readily acceptedo Easy to perform

o 50% of women who receive cervical cancer diagnosis never had a pap smearo 10% had not been

screened in 5 years

Timing of Screeningo Three years after initiation of sexual

intercourse but no later than 21 years of ageo Annual cytology screening for women

younger than 30o Women 30 years and older who have had

three negative cytology tests in a row may be screened every 2-3 years

o Women with HIV, immunosuppression, or DES exposure may require more frequent

screening

Discontinuation of Screeningo 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 Abnormalitieso Dysplasia thought to be precursor to

cervical cancero 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 resolveo 30% of CIN3

ASCUSAtypical Squamous Cells of Undetermined

Significance

o May be anything from inflammatory process to a neoplastic process

o Reflex HPV testing performedo If positive for high risk types should proceed

with further testingo If negative for high risk types may continue

yearly screening

Colposcopyo Done in follow-up to

abnormal smearo Magnified view of cervix

o Surfaced stained with acetic acid

o Biopsies taken to rule out advanced disease

Low Grade/CIN1o Usually caused by transient HPV infection

o 75-90% regresso Confirmed by coloposcopic biopsy

o Repeat pap smears every 6 months until 3 normal smears in a row then may return to

yearly screening

HGSIL/CIN2-3o Less chance of regression than

progressiono Usually destructive procedures or excision

performedo Cryotherapy

o Laser therapyo LEEP (loop electrosurgical excision procedure)

Human Papillomavirus (HPV)o 200 different subtypes

o More than 30 transmitted sexuallyo Primary causative agent of cervical cancer in over

95% of caseso Predominantly types 16 and 18 (70%)

o More than 75% sexually active women tested have been exposed to HPV by age 18-22

o Most people who have been exposed will display no symptoms and will clear the infection on their

own

Gardasil o Quadrivalent HPV vaccine

o Targets type 16,18 (cervical cancer) as well as types 6 and 11 (genital warts)

o Released June 2006o Approved for all women aged 9 to 26

o 3 doses ($120/dose)

Vaccine Efficacy

Vaginal & Vulvar Cancer

o The incidence of cancer of vagina and vulva is low i.e 0.5 and 2/100,000

women respectivelyo These cancers are common at an

advanced age. o No relevant information is known about

any connection between HRT and these cancers

Vaginal & Vulvar Cancer

o Lesion(s) on surface of vulva or labia; malignancy most often on labia majora or minora

o 3,870 new cases and 870 deaths in the US in 2005

o Rare disease 0.5% of all cancers in womeno 90% of vulvar cancers are squamous cell carcinomas

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

Vulvar

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

Risk Factors