Endometrial Cancer

Introduction

  • 32,800 cases/year
  • Most common female malignancy in the pelvis
  • 4th most common overall malignancy
  • Disease of post menopausal women primarily
  • Median age of uterine CA is 61 years

Risk Factors

  • True causes unknown
  • Associated with low fertility index
  • Disturbed menstruation
  • Obesity
  • Unopposed estrogen exposure (obesity, low parity, early menarche, late menopause)
  • Tamoxifen use (2.5 X)
  • Dietary fat
  • Granulosa theca cell ovarian tumors
  • DM, HTN, hypothroidism

Genetic Risk

  • Lynch Syndrome II – (HNPCC)
  • Activation of Ki – RAS oncogene
  • ERBB2 / Her-2 / neu protoonocogene over expression
  • Over expression of p53

Pathology — Many arise from endometrial hyperplasia

  • 80% are endometriod ACA
  • Many with squamous components
  • Adenocanthoma (benign adeno)
  • Adenosquamous carcinoma
  • Secretory
  • Ciliated Cell
  • Mucinous carcinoma
  • Serous carcinoma
  • Clear cell carcinoma
  • Squamous carcinoma
  • Undifferentiated carcinoma
  • Sarcoma
  • malignant mixed müllerian tumor

Endometrioid Carcinoma

  • Grade 1: < 5% solid areas
  • Grade 2: 5-50% solid areas
  • Grade 3: > 50% solid areas

Anatomy

Uterus divided structurally and functionally into two parts: the body and the cervix separated by the isthmus. Supportive ligaments: broad, utero-sacral, Round, cardinal
Blood Supply: Uterine A – Branch of the hypogastric enters the wall of the uterus at the isthmus ovarian A
Lymphatics: 4 drainage patterns
Superior fundus – ovarian vessels to PANS (left to L renal vein)
Mid/Inferior corpus – broad ligament – bifurcation of common iliac and external iliacs.
Fallopian tubes – PANs directly
Near round ligament/isthmus – inguinal/femoral nodes

Presenting Symptoms:

Abnormal bleeding, leukorrhea, vaginal discharge, pelvic pressure

Diagnostic Evaluation

Endometrial biopsy may render diagnosis but if not to be surgically staged with hysterectomy then Fractional D&C is diagnostic study of choice.
Consists of: 1) Curette endocervix
2) Dilate cervix
3) Curette endometrium
Additional Workup:
Hx + PE
CBC
UA
CXR
Ba enema if bowel symptoms present
Cystoscopy / proctoscopy if locally advanced
U/S and MRI – 70-90% accurate for muscle invasion
CA – 125

Prognostic Factors

Determined by GOG prospective trials 1984 and 1987
Uterine factors: tumor grade, depth of myometrial invasion, extension to cervix, cell type, LVSI.
Extrauterine factors: adnexal mets, intraperitoneal spread, + cytology, +LN’s.
Clinical: Stage, age, diploid better, PR+ better, Her-2/neu worse

Pelvic and PAN Lymph Nodes

Overall incidence 11% seen in 1987 GOG-33 (Creasman) study of Stage I and II pts (clinical)

% Pelvic LN
Invasion G1 G2 G3
Inner 1/3 3% 5% 9%
Middle 1/3 0% 5% 4%
Outer 1/3 11% 19% 34%

Paraaortic LN risk is about 50% of Pelvic LN risk

% Paraaortic LN
Invasion G1 G2 G3
Inner 1/3 1% 4% 4%
Middle 1/3 5% 0% 0%
Outer 1/3 6% 14% 23%

5-yr recurrence-free survival based on nodal status

5y RFS
Node negative 90%
Pelvic nodes + 75%
PA nodes + 35%

Age

Older patients have atrophic uterus with thin myometrium / tumors become invasive, deep and higher stage. Also worse for older patients stage for stage, with higher risk of poor histology and serous tumors.

Hormone Receptor Levels

In general patients with receptor positive tumors have a significantly better DFS.
Receptor status also predicts likelihood of hormonal therapy in pts. who have relapsed.

Frequency of nodal metastasis among risk factors
Risk factor Pelvic no. (%) Aortic no. (%)
Histology
Endometrioid adenocarcinoma 9% 5%
Others 9% 18%
Grade
1 Well 3% 2%
2 Moderate 9% 5%
3 Poor 18% 11%
Myometrial invasion
Endometrial 1% 1%
Superficial 5% 3%
Middle 6% 1%
Deep 25% 17%
Site of tumor location
Fundus 8% 4%
Isthumus-cervix 16% 14%
Adnexal Involvement
Negative
Positive 30% 20%
Capillary-like space involvement
Negative 7% 4%
Positive 23% 16%
Other extrauterine metastasis
Negative 7% 4%
Positive 51% 23%
Peritoneal cytology
Negative 7% 4%
Positive 25% 19%
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