Endometrial Cancer Flashcards
Incidence/Statistics of Endometrial Cancer
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
What is the classification of endometrial carcinomas?
2 Major types based on light microscopic appearance, clinical behavior and epidemiology.
What is Type I endometrial carcinoma?
Endometrioid histology
80% of endometrial carcinoma
Estrogen responsive, preceded by an atypical or complex endometrial hyperplasia
Favorable prognosis
What is Type II endometrial carcinoma
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
What are the different types of non-endometrioid histology?
serous, clear cell, mucinous, squamous cell, transitional cell, mesonephric, undifferentiated
What are endometrioid carcinoma?
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.
Serous and clear cell carcinoma
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
Common genetic abnormalities in endometrioid neoplasms
microsatellite instability, K-ras, PTEN, defects in DNA mismatch
Common genetic abnormalities in non-endometrioid neoplasms
p53
Pelvic/peritoneal washing cytology
Assess microscopic peritoneal spread
Most will not change management based on positive peritoneal wash
Indicates higher risk of recurrence
Endometrial cancer and races
Incidence higher in whites
But mortality is 2x higher in blacks - higher incidence of aggressive cancer subtypes, access and quality of care
Average age of uterine cancer diagnosis is:
61
Between 55-64 - >30% cases - highest distribution
Between age 50-70, women have what % risk of being diagnosed with uterine cancer? Lifetime risk?
- 4%
2. 6%
When are uterine cancer most commonly diagnosed?
68% confined to primary site
20% spread to regional organs/lymph nodes
8% distant metastasis
Endometrioid major risk factor
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
Endometrioid risks: drugs?
Tamoxifen in postmenopausal
SERM - agonist at endometrium
Lack of evidence in premenopausal women
only in age > 55
Estrogen-associated risk factors for endometrioid cancer
- Obesity (peripheral conversion of androstenedione to estrone)
- Chronic anovulation (PCOS, thyroid dysfunction, elevated prolactin levels)
- Early menarche/late menopause
- E-secreting tumor (granulosa cell tumors)
- Diabetes (hyperinsulinemia, insulin resistance, elevated insulin-like growth factors)
Obesity and Endometrial cancer
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)
Other non-E related risk factors of endometrial cancer
- Family history (first degree relatives), no candidate gene identified consistently
- Lynch syndrome (AD germline mutation in DNA mismatch repair)
- BRCA1 (? tamoxifen)
Protective factors
- OCPs (progestin)
- childbearing at older age (35-39)
- smoking (hepatic metabolism of estrogens)
- physical activity (obesity?)
- Coffee, Green tea
Most common symptom
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
Physical exam for endometrial cancer
Size - hyperplasia/early do not have enlarged uterus.
Fixed, enlarged uterus may be consistent with uterine leiomyoma
Confirm source of bleeding is the uterus
Lab
betahCG to exclude pregnancy
hematocrit or clotting studies
Pelvic ultrasound
Postmenopausal women - endometrial thickness is < 4mm
Gold standard for evaluation for neoplasia is endometrial sampling
When to perform D&C
cannot tolerate office biopsy
heavy bleeding
very high risk of endometrial cancer (Lynch syndrome)
ensure focal lesions are identified and biopsied
Endometrial sampling
Office endometrial biopsy - highly effective at diagnosing endometrial hyperplasia
Differential diagnosis for endometrial carcinoma
Atrophy Endometrial polyp Fibroids Cervical neoplasia Bleeding from anus/rectum
Pregnancy/ectopic pregnancy
Menopausal transition
What is the sensitivity for endometrial sampling?
90% or higher
False negative if hx of colorectal cancer, polyps, obesity
Endometrial cancer screening
No high quality data to support screening to reduce cancer mortality
Except in Lynch syndrome
Biopsy is uncomfortable and invasive
Most useful in predicting extrauterine spread of endometrial carcinoma
CA 125
Useful after initial treatment
If patient cannot be surgically staged?
Contrast-enhanced MRI for detecting myometrial invasion and cervical involvement
Also best modality for detecting lymph node metastases
How is endometrial cancer staged?
Surgically staged
Total extrafascial hysterectomy with BSO with (selective) pelvic/paraaortic lymph node dissection is standard staging
Stages of Endometrial cancer
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
Is endometrial cancer curative?
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)
Intraoperative gross inspection and frozen section
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
When should nodes be resected?
Serous, clear cell, high-grade histology
Myometrial invasion greater than 50%
Large tumor (>2 cm in diameter or filling endometrial cavity)
Which nodes are resected
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
Cervical involvement
Historically radical hysterectomy
Simple hysterectomy with lymphadenectomy (lymphovascular space invasion better predictor of parametrial extension)
Laparoscopic
Faster recovery time
Limitation - dissect paraaortic nodes above IMA
Inoperable patients or refusing surgery
Stage I disease - primary pelvic radiation may be acceptable
Patient who wants to preserve fertility?
Stage I grade I may be candidate for treatment with progestin therapy.
5 year survival
Stage I - 80-90%
Stage II - 70-80%
Stage III/IV - 20-60%
Medium risk patients
Invades myometrium or cervical stromal invasion
Candidates for adjuvant radiation therapy
No role for chemotherapy
High risk patients
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
Surveillance protocols
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
Symptoms of recurrence
Bleeding, abdominal/pelvic pain, persistent cough, unexplained weight loss
When do recurrences occur?
68-100% within 3 years
Most common in vaginal vault, pelvis, abdomen, lung
What is stage 2 endometrial cancer?
Invades connective tissue of cervix
What is stage 3a endometrial cancer?
Serosa or adnexa through extension or metastasis
What is stage 3b endometrial cancer?
Vaginal involvement
What is stage 4 endometrial cancer?
Invades bladder mucosa
