Female Reproductive System

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Female Reproductive System Kristine Krafts, M.D.
October 27, 2008
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Female Reproductive System Outline

• Cervix
• Uterus
• Ovaries
• Breast

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Female Reproductive System Outline

• Cervix
• Cervical carcinoma

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Cervical Carcinoma
Things you must know

• Once the most common cancer in women now not
  even in top 10.
• 13th in cancer deaths in women
• Decreases due to Pap test!
• At the same time, precursor lesions are
  increasing (early detection!)

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Cervical Carcinoma
Cervical intraepithelial neoplasia (CIN)

• Precursor to carcinoma
• Almost all carcinomas arise in CIN but not all
  cases of CIN progress to carcinoma!
• Three grades
• CIN I mild dysplasia (half regress, 20
  progress)
• CIN II moderate dysplasia
• CIN III severe dysplasia (30 regress, 70
  progress)
• The higher the grade, the more likely the lesion
  will progress to carcinoma

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Cervical Carcinoma
Risk Factors

• Early age at first intercourse
• Multiple sexual partners
• A male partner with multiple previous partners
• Persistent infection with high-risk HPV
• Smoking
• Immunodeficiency

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Cervical Carcinoma
Association with HPV

• HPV is detectable in almost all CIN and cancer.
• High-risk types
• 16, 18, 45, 31
• Found in carcinomas
• Integrate into genome, inactivate p53, RB
• Low-risk types
• 6,11
• Found in condylomas (benign lesions)
• Do not integrate into genoma

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Development of transformation zone
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Transformation zone
Normal cervix, young adult
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Transformation zone
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Spectrum of cervical intraepithelial neoplasia
(CIN)
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Normal (left) turning into CIN (right)
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normal
CIN I
CIN II
CIN III
Cytology of CIN (Pap smear)
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normal
CIN I
CIN II
CIN III
High-grade dysplasia
Low-grade dysplasia
Cytology of CIN (Pap smear)
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Cervical Carcinoma
Invasive cervical carcinoma

• Most cases are squamous, arising from CIN
• Small number are adenocarcinomas
• Peak age 45 (10-15 years after CIN develops!)
• Spreads slowly
• Most cases are diagnosed early
• Mortality is related to stage
• stage 0 (preinvasive) 100 5 year survival
• stage 4 10 5 year survival

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Cervical carcinoma
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Cervical carcinoma
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Female Reproductive System Outline

• Cervix
• Uterus
• endometriosis
• endometrial hyperplasia
• tumors

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Endometriosis

• Location of endometrial glands outside uterus
• Usually peritoneum, rarely lymph nodes
• Endometrium undergoes cyclic bleeding
• Causes scarring, pain, sometimes sterility.
• How does endometrium get out?

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Endometriosis in ovary (chocolate cyst)
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Endometrial Hyperplasia

• Proliferation of endometrium due to estrogen
  excess
• Risk factors anovulatory cycles, obesity,
  estrogen-producing ovarian tumors, exogenous
  hormone use
• Three categories simple, complex, and atypical
• The more severe the hyperplasia, the greater the
  chance that it will evolve into carcinoma

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Normal endometrium
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Simple
Complex
Atypical
Endometrial hyperplasia
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Uterine Tumors
Leiomyoma

• Fibroid
• Benign tumor of smooth muscle
• Common!
• Stimulated by estrogen
• Menorrhagia, metrorrhagia, or asymptomatic

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Uterine Tumors
Leiomyosarcoma

• Malignant tumor of smooth muscle
• Necrotic, with atypical cells and lots of mitoses
• Often recur after surgery
• Many metastasize, especially to lungs
• 5 year survival 40

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Leiomyoma
Leiomyosarcoma
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Leiomyoma
Leiomyosarcoma
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Uterine Tumors
Endometrial carcinoma

• Peak age 55-65 (not before 40)
• Frequently arises in endometrial hyperplasia
• Risk factors obesity, nulliparity, estrogen
  replacement
• Symptoms leukorrhea, irregular bleeding
• Metastasizes late

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Endometrial adenocarcinoma
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Female Reproductive System Outline

• Cervix
• Uterus
• Ovaries

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Origin of Ovarian Tumors
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Benign Ovarian Tumors
Cystadenoma

• Benign tumor derived from surface epithelium
• Repeated ovulation, scarring, infolding of
  epithelium leads to cysts, which can undergo
  neoplastic transformation
• Typically large, occasionally bilateral

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Patient with ovarian cystadenoma
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Patient with ovarian cystadenoma
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Patient with ovarian cystadenoma
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Ovarian cystadenoma
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Ovarian cystadenoma
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Ovarian cystadenoma
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Benign Ovarian Tumors
Teratoma

• Benign tumor with differentiation along all three
  germ cell layers (ectoderm, endoderm, mesoderm)
• Usually cystic, with skin inside (dermoid cyst)
• Sebaceous material, matted hear, teeth, bone
• Malignant variant has immature tissues

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Teratoma
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Teratoma
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Ovarian Cancer

• 23,000 new cases / 15,000 deaths in 2007
• 5th commonest, 5th most deadly cancer in women
• Danger produces no signs until advanced
• Peak age 50
• Most are cystadenocarcinomas

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Papillary cystadenocarcinoma
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Papillary cystadenocarcinoma
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Ovarian Cancer

• Symptoms
• feeling of fullness or bloating
• pelvic pain
• back pain
• abnormal menses
• Risk factors
• nulliparity
• family history (BRCA gene mutation)
• NOT using oral contraceptives!

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Ovarian Cancer

• Treatment surgery, radiation, chemotherapy
• Prognosis depends on stage
• cancer confined to the ovary 5y survival 70
• cancer through ovarian capsule 5y survival 13

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Female Reproductive System Outline

• Cervix
• Uterus
• Ovaries
• Breast
• Fibrocystic change
• Tumors

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Breast

• Many breast diseases present as lumps
• Most lumps represent benign things
• but a lump always needs to be evaluated
• Ultrasound, mammography, fine needle aspiration,
  and biopsy are the usual methods

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Most breast lumps are benign
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Fibrocystic Change

• Two kinds nonproliferative and proliferative
  change
• Cause exaggeration of normal breast cycles
• Rarely associated with increased cancer risk
• Very common (present in most women at autopsy)
• Called fibrocystic change, not fibrocystic
  disease

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Fibrocystic Change

• Nonproliferative fibrocystic change
• increased stroma
• dilation of ducts, formation of cysts
• Proliferative fibrocystic change
• hyperplasia of breast epithelium
• If epithelium shows atypia, 5x ? risk of cancer

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Fibrocystic change
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Normal breast
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Nonproliferative fibrocystic change
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Proliferative fibrocystic change
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Fibroadenoma

• Most common benign breast tumor
• Stimulated by estrogen
• Peak incidence 20s
• Solitary, discrete, moveable mass
• Fibrous tissue with compressed ducts and lobules

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Fibroadenoma
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Fibroadenoma
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Breast Carcinoma

• 180,00 new cases / 40,000 deaths in 2007
• Most common, 2nd deadliest cancer in women
• Lifetime risk 1 in 8
• 75 of patients are gt50
• Rate was increasing but now stable

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Breast Carcinoma
Risk Factors

• Age
• Family History
• Increased estrogen exposure
• Obesity
• Alcohol consumption
• High-fat diet

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Breast Carcinoma
Family History

• 5-10 of all cases are hereditary
• Worry if first degree relative with breast cancer
• Most have BRCA-1 or BRCA-2 mutations
• Tumor suppressor genes help repair DNA
• Genetic testing difficult
• Most carriers get cancer by age 70

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Breast Carcinoma
Typical Clinical Findings

• If discovered by palpation
• Solitary, painless, moveable mass
• 2-3 cm in diameter
• Axillary nodes positive in 50 of patients
• If discovered by mammography
• 1 cm in size
• Axillary nodes positive in only 15 of patients
• With disease progression
• Fixation to chest wall
• Adherence to overlying skin
• Peau dorange

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Size of typical palpable breast lump
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Advanced breast carcinoma fixation to skin
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Peau dorange
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Breast Carcinoma
Histologic types

• Non-invasive
• Ductal carcinoma in situ (DCIS)
• Lobular carcinoma in situ (LCIS)
• Invasive
• Ductal
• Lobular
• Medullary
• Mucinous
• Tubular
• Others

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Breast Carcinoma
Non-Invasive Breast Carcinoma

• Neoplastic cells fill ducts (DCIS) or lobules
  (LCIS) but do not breach basement membrane
• Incidence has increased with mammography
• If untreated, over 1/3 will develop invasive
  carcinoma
• With treatment, prognosis is excellent

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Normal breast
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Lobular carcinoma in situ
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Breast Carcinoma
Invasive Breast Carcinoma

• Ductal (or not otherwise specified) carcinoma
• Lobular carcinoma
• Inflammatory carcinoma
• Medullary carcinoma
• Mucinous carcinoma
• Tubular carcinoma

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Invasive breast carcinoma
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Invasive ductal breast carcinoma low grade
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Invasive ductal breast carcinoma high grade
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Inflammatory breast carcinoma
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Inflammatory breast carcinoma
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Breast Carcinoma
Prognostic Factors

• Size of tumor
• Lymph node involvement
• Distant metastases
• Grade of tumor
• Histologic type of tumor

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Sentinel node biopsy
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TNM staging system for breast cancer
Overall stage Stage 0 Stage I Stage II Stage
III Stage IV
T DCIS lt2 cm lt5 cm gt5 cm lt5 cm gt5 cm Any T Any
T Any T
N 0 0 lt3 0 4 1 10 Any N Any N
M M0 M0 M0 M0 M0 M0 M0 skin or chest wall M1
5y survival 92 87 75 46 13