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Gyn Malignancies


									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          woman with:
                      Vaginal bleeding
                 Abnormal vaginal discharge
Gynecologic Malignancies 2005

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

              o  Mammography
                o Pap Smears
            o Diabetes screening
                o Colonoscopy
             o Thyroid screening
       o   Prostate specific antigen
The Uterus
             o  Also known as fibroids
o   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
      o Half to one third of hysterectomies
  o   Majority are asymptomatic (50-65%)
       o When symptomatic can cause:
                   • Metrorrhagia
                   • Menorrhagia
                       • Pain
                    • Infertility

               o Cause unknown
          o   Hormonally responsive
              o Commonly multiple
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
     o Endometrial glands/stroma outside the
                 endometrial cavity
     o 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 pain
         o 40% of women with infertility

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
                 o Dysmenorrhea
                  o Dyspaurenia
                   o Infertility
               o Abnormal bleeding
                o Cyclic pelvic pain

o   Severity of symptoms does not correlate with
              amount of endometriosis
The Faces of Endometriosis
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
     o  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   25% premenopausal
                o   75% postmenopausal
         o   75% at Stage I at diagnosis
              o 75% adenocarcinomas
Risk Factors for Endometrial Cancer

     o Early menarche                          o   Diabetes
          (<age 12)                      o Age greater than 40
    o Late menopause                       o Caucasian women
           (>age 52)                       o Family history of
 o Infertility or nulliparous               endometrial cancer or
                                          hereditary nonpolyposis
o Obesity (>30# overweight)
                                            colon cancer (HNPCC)
o Treatment with tamoxifen
                                o       Personal history of breast or
      for breast cancer                         ovarian cancer
  o Estrogen replacement
                                    o    Prior radiation therapy for
     therapy (ERT) after                         pelvic cancer
  o Diet high in animal fat
Endometrial Cancer
         o  Most common symptom is
             irregular bleeding (90%)
         o No effective screening test
       o Endometrial biopsy standard of
               o May require D&C
          o Surgery is first choice for
      o Overall 5 year survival rate 65%
        with 85% recurrences within first
                      3 years
Dermoid Cyst

               o   Ovarian cyst containing
                    hair, teeth, cartilage
               o   Stem cells that “forgot”
                          to migrate
Radiologic Differences
           Benign                       Malignant

    o Simple cysts < 10 cm     o   Solid or cystic & solid
     o Septations < 1mm        o   Multiple Septations >
            thickness                     3mm size
         o Unilateral                  o Bilateral
o   Calcifications esp teeth            o Ascites
    o Gravity dependent
        layering of cyst
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

    75% Patients have disease beyond the ovary at time
            of diagnosis (Stage III or higher)
Ovarian Cancer
                         o  25,000 new cases/yr
                    o   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
                                    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

   Oral contraceptives have been found to have a
        protective effect for ovarian cancer
                 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
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          Benign Conditions
   o Epithelial Ovarian     o Normal & ectopic
           Cancer                  pregnancy
 o Fallopian Tube Cancer      o Endometriosis
  o Endometrial Cancer           o Fibroids
  o Endocervical Cancer    o Pelvic Inflammatory
   o Pancreatic Cancer              Disease
      o Lung Cancer            o Pancreatitis

     o Breast Cancer            o Peritonitis

      o Colon Cancer             o Cirrhosis
                            o Recent abdominal
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
o   Radiation plays little role in the treatment of
                   ovarian cancers

       Stage I     80-95%
       Stage II    40-70%
       Stage III   30%
       Stage IV    < 10%
Germ Cell Tumors
           o  15-20% Ovarian tumors
      o Arise from totipotential germ cells
                o 95% are benign
         o Women in their teens and 20s
  o   Rapidly enlarging adnexal mass and pain
  o   Diagnosed earlier and treatment usually
       limited to removal of affected ovary
        o Highly curable with surgery and
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
      o The endocervix epithelium contains
            receptors for sex hormones
Cervical Cancer Statistics
  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
 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
Risk Factors for Cervical Cancer
                 o Cigarette smoking
          o High number of sexual partners
           o Early onset of sexual activity
    o   History of sexually transmitted diseases

o   In patients with HIV invasive cervical cancer
       is considered an AIDS defining illness
o   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 Smear
              o 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
                o 10% had not been
                  screened in 5 years
Timing of Screening
     o  Three years after initiation of sexual
    intercourse but no later than 21 years of age
o   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
o   Women with HIV, immunosuppression, or DES
        exposure may require more frequent
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
Cytologic Abnormalities
o   Dysplasia thought to be precursor to cervical
o   On average takes 7 years for a CIN1 lesion to
    progress to a cancer and 4 years for a CIN2
      o 75-90% of CIN1 lesions will resolve
      o 50% of CIN2 spontaneously resolve
                  o 30% of CIN3
    Atypical Squamous Cells of Undetermined

o  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  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
Low Grade/CIN1
 o   Usually caused by transient HPV infection
                o 75-90% regress
       o Confirmed by coloposcopic biopsy
 o   Repeat pap smears every 6 months until 3
     normal smears in a row then may return to
                  yearly screening
o    Less chance of regression than progression
 o   Usually destructive procedures or excision
                       o  Cryotherapy
                       o Laser therapy
     o   LEEP (loop electrosurgical excision procedure)
Human Papillomavirus (HPV)
               o 200 different subtypes
          o More than 30 transmitted sexually
 o   Primary causative agent of cervical cancer in over
                       95% of cases
         o 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
            o Quadrivalent HPV vaccine
o   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)
Vaccine Efficacy
Vaginal & Vulvar Cancer
Vaginal & Vulvar Cancer

 o  The incidence of cancer of vagina and vulva
      is low i.e 0.5 and 2/100,000 women
  o These cancers are common at an advanced
 o No relevant information is known about any
   connection between HRT and these cancers
 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 women
           o    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
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

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