Endometrial Cancer

Question 1

Incidence/Statistics of Endometrial Cancer

Answer 1

Most common cancer of female reproductive organs in developed countries (cervical in developing)
American Cancer Society estimates for uterus cancers in US for 2013 (2011 numbers)
- 50,000 new cases of cancer will be diagnosed
- 8000 will die from cancer

Question 2

What is the classification of endometrial carcinomas?

Answer 2

2 Major types based on light microscopic appearance, clinical behavior and epidemiology.

Question 3

What is Type I endometrial carcinoma?

Answer 3

Endometrioid histology
80% of endometrial carcinoma
Estrogen responsive, preceded by an atypical or complex endometrial hyperplasia
Favorable prognosis

Question 4

What is Type II endometrial carcinoma

Answer 4

10-20% of endometrial carcinomas
Grade 3 endometrioid and non-endometrioid histology
Often high-grade, poor prognosis, and not associated with estrogen stimulation.
Precursor lesion is rarely identified

Question 5

What are the different types of non-endometrioid histology?

Answer 5

serous, clear cell, mucinous, squamous cell, transitional cell, mesonephric, undifferentiated

Question 6

What are endometrioid carcinoma?

Answer 6

Well-differentiated, gland forming neoplasms
Graded by gland formation and nuclear grade

Grade 1: no more than 5% solid (nonglandular growth)
G2: 6-50% solid growth
Grade 3>50% solid growth
Squamous metaplasia not counted.

Question 7

Serous and clear cell carcinoma

Answer 7

Myometrial and vascular invasion more common
Poorer prognosis

Serous - papillary architect that resembles serous carcinoma of vary with nuclear atypia and psammoma bodies
Clear cell: clear cytoplasm due to glycogen

Question 8

Common genetic abnormalities in endometrioid neoplasms

Answer 8

microsatellite instability, K-ras, PTEN, defects in DNA mismatch

Question 9

Common genetic abnormalities in non-endometrioid neoplasms

Answer 9

p53

Question 10

Pelvic/peritoneal washing cytology

Answer 10

Assess microscopic peritoneal spread
Most will not change management based on positive peritoneal wash

Indicates higher risk of recurrence

Question 11

Endometrial cancer and races

Answer 11

Incidence higher in whites

But mortality is 2x higher in blacks - higher incidence of aggressive cancer subtypes, access and quality of care

Question 12

Average age of uterine cancer diagnosis is:

Answer 12

61

Between 55-64 - >30% cases - highest distribution

Question 13

Between age 50-70, women have what % risk of being diagnosed with uterine cancer? Lifetime risk?

Answer 13

1. 4%

2. 6%

Question 14

When are uterine cancer most commonly diagnosed?

Answer 14

68% confined to primary site
20% spread to regional organs/lymph nodes
8% distant metastasis

Question 15

Endometrioid major risk factor

Answer 15

Estrogen-responsive
Long-term exposure to endogenous or exogenous estrogen without opposing progestins

Multiple case controls found increased endometrial carcinoma with unopposed estrogen therapy 1.1-15 RR; 20-50% of women have endometrial hyperplasia after 1 year of use

Women’s health initiative randomized trial - hormone therapy not increase risk

Question 16

Endometrioid risks: drugs?

Answer 16

Tamoxifen in postmenopausal
SERM - agonist at endometrium

Lack of evidence in premenopausal women
only in age > 55

Question 17

Estrogen-associated risk factors for endometrioid cancer

Answer 17

1. Obesity (peripheral conversion of androstenedione to estrone)
2. Chronic anovulation (PCOS, thyroid dysfunction, elevated prolactin levels)
3. Early menarche/late menopause
4. E-secreting tumor (granulosa cell tumors)
5. Diabetes (hyperinsulinemia, insulin resistance, elevated insulin-like growth factors)

Question 18

Obesity and Endometrial cancer

Answer 18

alterations in insulin-resistance - increased risk of endometrial carcinoma

increased risk of dying - uncertain pathophysiology, continued stimulation of metastatic cells by endogeneous; obesity-associated conditions (cardiovascular/diabetes)

Question 19

Other non-E related risk factors of endometrial cancer

Answer 19

• Family history (first degree relatives), no candidate gene identified consistently
• Lynch syndrome (AD germline mutation in DNA mismatch repair)
• BRCA1 (? tamoxifen)

Question 20

Protective factors

Answer 20

• OCPs (progestin)
• childbearing at older age (35-39)
• smoking (hepatic metabolism of estrogens)
• physical activity (obesity?)
• Coffee, Green tea

Question 21

Most common symptom

Answer 21

Abnormal uterine bleeding - intermenstrual bleeding who are ovulatory, frequenty, heavy (>80 ml) or prolonged
75-90% women

Amount of bleeding does not correlate with risk of cancer

Age 45yo as cutoff

Question 22

Physical exam for endometrial cancer

Answer 22

Size - hyperplasia/early do not have enlarged uterus.
Fixed, enlarged uterus may be consistent with uterine leiomyoma

Confirm source of bleeding is the uterus

Question 23

Lab

Answer 23

betahCG to exclude pregnancy

hematocrit or clotting studies

Question 24

Pelvic ultrasound

Answer 24

Postmenopausal women - endometrial thickness is < 4mm

Gold standard for evaluation for neoplasia is endometrial sampling

Question 25

When to perform D&C

Answer 25

cannot tolerate office biopsy heavy bleeding very high risk of endometrial cancer (Lynch syndrome) ensure focal lesions are identified and biopsied

Question 26

Endometrial sampling

Answer 26

Office endometrial biopsy - highly effective at diagnosing endometrial hyperplasia

Question 27

Differential diagnosis for endometrial carcinoma

Answer 27

``` Atrophy Endometrial polyp Fibroids Cervical neoplasia Bleeding from anus/rectum ``` Pregnancy/ectopic pregnancy Menopausal transition

Question 28

What is the sensitivity for endometrial sampling?

Answer 28

90% or higher | False negative if hx of colorectal cancer, polyps, obesity

Question 29

Endometrial cancer screening

Answer 29

No high quality data to support screening to reduce cancer mortality Except in Lynch syndrome Biopsy is uncomfortable and invasive

Question 30

Most useful in predicting extrauterine spread of endometrial carcinoma

Answer 30

CA 125 | Useful after initial treatment

Question 31

If patient cannot be surgically staged?

Answer 31

Contrast-enhanced MRI for detecting myometrial invasion and cervical involvement Also best modality for detecting lymph node metastases

Question 32

How is endometrial cancer staged?

Answer 32

Surgically staged | Total extrafascial hysterectomy with BSO with (selective) pelvic/paraaortic lymph node dissection is standard staging

Question 33

Stages of Endometrial cancer

Answer 33

2010 classification changed 1A (tumor limited to endometrium or invades less than one-half of myometrium) 1B (tumor invades 1/2 or more of myometrium) Better able to predict prognosis

Question 34

Is endometrial cancer curative?

Answer 34

Surgery alone usually curative for low risk disease (endometrioid histology grade 1,orr 2, confined to endometrium, no other risk factors for persistence and recurrence)

Question 35

Intraoperative gross inspection and frozen section

Answer 35

frozen section - not consistently high concordance, especially in low-stage and low-grade disease; variable between pathologies. Large study - grade on final path was higher than that from intraoperative frozen

Question 36

When should nodes be resected?

Answer 36

Serous, clear cell, high-grade histology Myometrial invasion greater than 50% Large tumor (>2 cm in diameter or filling endometrial cavity)

Question 37

Which nodes are resected

Answer 37

Distal 1/2 of common iliac artery Proximal 1/2 of external iliac artery Distal 1/2 of obturator fat pad anterior to obturator nerve New research into sentinel node biopsy - further study needed

Question 38

Cervical involvement

Answer 38

Historically radical hysterectomy | Simple hysterectomy with lymphadenectomy (lymphovascular space invasion better predictor of parametrial extension)

Question 39

Laparoscopic

Answer 39

Faster recovery time | Limitation - dissect paraaortic nodes above IMA

Question 40

Inoperable patients or refusing surgery

Answer 40

Stage I disease - primary pelvic radiation may be acceptable

Question 41

Patient who wants to preserve fertility?

Answer 41

Stage I grade I may be candidate for treatment with progestin therapy.

Question 42

5 year survival

Answer 42

Stage I - 80-90% Stage II - 70-80% Stage III/IV - 20-60%

Question 43

Medium risk patients

Answer 43

Invades myometrium or cervical stromal invasion Candidates for adjuvant radiation therapy No role for chemotherapy

Question 44

High risk patients

Answer 44

Stage III disease regardless of grade Uterine serous/clear cell carcinoma of any stage Receive chemo with or without radiation therapy given high risk of distant and locoregional relapse

Question 45

Surveillance protocols

Answer 45

Monitoring for symptoms (70%) Routine use of CA 125 (varies) Review of symptoms and PE every 3-6 months for 2 years, then every 6 months or annually. Vaginal cytology every 6 months for 2 years, then annually Genetic counseling for lynch

Question 46

Symptoms of recurrence

Answer 46

Bleeding, abdominal/pelvic pain, persistent cough, unexplained weight loss

Question 47

When do recurrences occur?

Answer 47

68-100% within 3 years | Most common in vaginal vault, pelvis, abdomen, lung

Question 48

What is stage 2 endometrial cancer?

Answer 48

Invades connective tissue of cervix

Question 49

What is stage 3a endometrial cancer?

Answer 49

Serosa or adnexa through extension or metastasis

Question 50

What is stage 3b endometrial cancer?

Answer 50

Vaginal involvement

Question 51

What is stage 4 endometrial cancer?

Answer 51

Invades bladder mucosa