ENDOMETRIAL

CANCER
DR DOBGIMA W. PISOH
O B / GY N
B A M E N D A R E G I O N A L H O S P I TA L
M AY 2 0 1 8
Plan
•Introduction
•Pathogenesis and natural history
•Epidemiology
•Diagnosis
•Classification
•Differential diagnosis
•Management
•Follow up
•Prognosis
•Conclusion
INTRODUCTION
•Endometrial cancer: group of malignant tumors arising from the uterine
endometrium
•4th most frequent gynecological cancer in CMR (3%) after breast, cervical and
ovarian cancers
•Affects principally the menopause and perimenopausal women
•More common among white women than black women,
•Prognosis is generally good because majority of patients diagnosed in an early
stage (postmenopausal women signal bleeding early)
 INTRODUCTION
•The endometrium (uterine mucosa): inner-most of the 3 layers of the
body of the uterus (womb)
•The endometrium is 0.5 – 5 mm thick
•The endometrium varies with stage of development:
◦ Reproductive life: 3 phases (menstruation, proliferative, secretory)
◦ Post-menopause: atrophic, < 5 mm
•Histology of the endometrium (non pregnant)
◦ Epithelium: single-layered, columnar, with tubular glandular folds.
Connective tissue: surrounds the uterine glands, contains blood
vessels (spiral arteries, veins)
INTRODUCTION
After menopause, progressively
◦ Atrophy
◦ Flattening of the epithelium
◦ ↓ Glands
◦ Fibrosis of interglandular tissue
PATHOGENESIS AND NATURAL
HISTORY
•An estrogen-driven pathway - Type I
•Another pathway seemingly unrelated to hormones - Type II
 PATHOGENESIS AND NATURAL
HISTORY
1) Type I carcinomas (70-80%),
◦ Estrogen dependent pathway
◦ arise in background of hyperplastic endometrium, (slow growing and takes 10
– 12 years from time it begins to develop a cancer)
◦ Associated with hyperlipidemia, obesity, and signs of hyperestrogenism,
◦ have better prognosis
 PATHOGENESIS AND NATURAL
HISTORY
2) Type II carcinomas (10-20%)
• estrogen-unrelated pathway
• arise in the background of atrophic endometrium.
• occurs at an older age, - menopause (5-10 yrs later than type I)
• deep myometrial invasion
• high degree of metastasis
• poor prognosis
PATHOGENESIS AND NATURAL
HISTORY
Common routes of metastasis
•Direct/local ; local extension towards the cervix, endometrium and beyond the
uterus including bowel and bladder
•Lymphatic – to pelvic, paraaortic, and rarely inguinal lymph nodes
•Hematologic; lungs liver, bone and rarely brain
•Peritoneal/ transtubal – intraperitoneal implants
 EPIDEMIOLOGY
• Often diagnosed in early stages:
• Affects principally perimenauposal and post menauposal subjects; peak at 65* yrs
• 25% diagnosed before the menopause
 ANALYTIC EPIDEMIOLOGY

RISK FACTORS
Age > 40yrs Breast cancer
Higher level of education or income Ovarian cancer
White race Obesity
Nulliparity Late age at natural menopause ( > 52yrs)
History of infertility Early age at menarche ( < 12yrs)
Menstrual irregularities
ANALYTIC EPIDEMIOLOGY
PROTECTIVE FACTORS
Age: young age for type I Breast feeding by ovulation suppression
Reduced oestrogen stimulation Diet with high fruits & vegetables
Fertility
late menarche
Early menopause
CIGARETTE/SMOKING: Physical exercise

Combined Oral contracep : risk drop by ~50%

 DIAGNOSIS
•75% of women with endometrial cancer are postmenopausal
Symptoms
•Abnormal uterine bleeding:
◦ postmenopausal bleeding. (90 % of cases)
◦ Heavy frequent menstrual periods or intermenstrual bleeding during
perimenopause
DIAGNOSIS
Other symptoms
◦ Lower abdominal pain or pelvic cramping
◦ Post menopausal discharge
◦ Mass efffect of enlarged uterus
◦ Pelvic pressure,
◦ Increased urinary frequency,
◦ Difficulty emptying bladder,
◦ Constipation
 DIAGNOSIS
•Physical examination
•General exam
• Calculation of the body mass index,
• Look for elements of metastasis (enlarged liver, ascitis etc)
•Pelvic examination findings may be entirely normal
•Speculum is done to confirm the origin of bleeding
•uterus and adnexa should be palpated for uterine size and position, as well as
for any suspicious masses.
•Check for inguinal lymph nodes
 DIAGNOSIS
Paraclinical examination
1) Pap smear
2) Vaginal ultrasonography (+ Doppler)
•performed 1-2 days after menstruation stops when endometrium
considered to be thinnest
•Cut off of 4 mm for endometrial thickness in menopausal – need a biopsy
 DIAGNOSIS
Paraclinical examination
3) Hydroultrasonography
•useful when ultrasonography suggests a focal lesion, or when abnormal
bleeding persists despite normal initial workup.
4) Hysteroscopy -Evaluates the uterine cavity
5) MRI
6) Computed Tomography – for locating distant metastasis better
DIAGNOSIS
For definitive diagnosis it is necessary to do a biopsy
•Endometrial biopsy (Pipelle, Novak curette,)
•Hysteroscopically directed biopsy
•Dilatation and curettage
 DIAGNOSIS
Histologic types
•Type I
• endometrioid adenocarcinoma
•Type II
• serous carcinoma
• Clear cell carcinoma
• mucinous carcinoma
• serous carcinoma
• mixed types of carcinoma
• undifferentiated carcinoma
DIAGNOSIS
EXTENSION Work – Up
•Chest Xray: Lung metastasis especially if bone pain
•Abdominopelvic ultrasound: Liver metastasis
•Cystoscopy
•Rectosigmoidoscopy : GIT bleeding
•Abdominopelvic CT
•Intra Venous Urography – check kidney function
 DIAGNOSIS
Tumor markers
•For Monitoring of evolution
•CA 125:
•CA 15-3
•CA 19-9: mucinous tumors
 CLASSIFICATION (AJCC and FIGO 2010)
Primary tumor (T)
TNM FIGO stages Surgical-pathologic findings
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis* Carcinoma in situ (preinvasive carcinoma)
T1 I Tumor confined to corpus uteri
T1a IA Tumor limited to endometrium or invades less than one half of the myometrium
T1b IB Tumor invades one half or more of the myometrium
T2 II Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus**
T3a IIIA Tumor involves serosa and/or adnexa (direct extension or metastasis)
T3b IIIB Vaginal involvement (direct extension or metastasis) or parametrial involvement
IIIC Metastases to pelvic and/or para-aortic lymph nodes
IV Tumor invades bladder mucosa and/or bowel mucosa, and/or distant metastases
T4 IVA Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4)
 CLASSIFICATION (AJCC and FIGO 2010)
Regional lymph nodes (N)
TNM FIGO stages Surgical-pathologic findings
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 IIIC1 Regional lymph node metastasis to pelvic lymph nodes
N2 IIIC2 Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic
lymph nodes
Distant metastasis (M)
TNM FIGO stages Surgical-pathologic findings
M0 No distant metastasis
M1 IVB Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, or
lung, liver, or bone metastases; it excludes metastasis to para-aortic lymph nodes, vagina,
pelvic serosa, or adnexa)
DIFFERENTAL DIAGNOSIS
a) Premenopause
•Complications of early pregnancy, (threatened or incomplete abortion
•Uterine fibroids,
•Endometrial hyperplasia and polyps,
•Cervical polyps,
•Dysfunctional Bleeding
•Metastatic cancers from the bowel, bladder, and breast (rare)
DIFFERENTIAL DIAGNOSIS
b) Post menopause
◦ Atrophic vaginitis,
◦ Cancer of the cervix
◦ Sarcoma of the corpus uteri
◦ Endometrial hyperplasia and polyps,
MANAGEMENT
Goals
•Remove tumour
•Stop progression of tumoral activity
•Prevent complications and recurrence
•Ameliorate quality of life
MANAGEMENT
Methods
•Surgery
•Hormone therapy
•Chemotherapy
•Radiation therapy
METHODS
Surgery
•Total Abdominal Hysterectomy + Bilateral salpingoophorectomy (BSO)
•Laparoscopically assisted vaginal HRT + BSO

•Radical HRT + lymphadenectomy

•Radical HRT + lymphadenectomy ， removal of as much malignant tissue
as possible + omentectomy
METHODS
Hormone therapy
PROGESTOGENS
•Most endometrial cancers are hormonedependent.
•Medroxyprogesterone acetate: 400-600mg dly
ANTI-ESTROGENS = Tamoxifen (NOLVADEX®)
• Combined with progestogens to improve response.
METHODS
Chemotherapy
Has a limited place in advanced recurrence ．
Multiple agent therapy most common
METHODS
•Radiation therapy
• Adjuvant therapy:
• Local = Curietherapy
• External
 MANAGEMENT
Primary Prevention
- Fight against: Hypertension, Diabetes & obesity (exercise)
- Screening of high risk postmenopausal women
- Well manage dysovulations and PCOS
- Close follow-up of women on Tamoxifen
Secondary prevention
- Manage all endometrial hyperplasias and polyps
 FOLLOW UP
Schedule
- Every 3months for 1year
- Every 6months for 2years
- Every year from the 3rd year
Complete History + Physical Examination
Investigations:
- Chest X-Ray:
- CT-Scan : Symptomatic
- CA 125
- Pap smears
PROGNOSIS
•Overall 5 year survival of 70 ％ approximately ． Survival by Stage:
•Fortunately over 80 ％ of cases are diagnosed at Stage % 5yr survival
stage 1 ． IA 91
IB 88
IC 81
IIA 77
IIB 67
IIIA 60
IIIB 41
IIIC 32
IVA 20
IVB 5
PROGNOSIS
-Advanced age
-Comorbidities
-FIGO stage
-Histologic type:
-Degree of myometrial invasion
-Lymph node attainment
CONCLUSION
•Endometrial cancer; mainly cancer of women of the 6th and 7th decades of life
•Increasing incidence worldwide; associated with a high socio-economic status and
Advanced Age.
•Major risk factor ; hyperestrogenism (endogenous and exogenous)
• Post menopausal bleeding is endometrial cancer until proven otherwise
•The initial assessment consists of proper clinical evaluation, TVS and endometrial biopsy.
•Avoidance of hyperestrogenic states; positive towards prevention
•Mainstay of treatment is Surgery
•Adjuvant therapies (Hormono, chemo & radiotherapy):
REFERENCES
Dr Wen Li lecture notes on endometrial cancer
Compendum of selected publications. 2006.
Novak’s Gynecology: 12th Ed
Current diagnosis & treatment 2007.
Creasman WT. Revised FIGO staging for carcinoma of the vulva, cervix and endometrium. Inter J Gynecol and Obstet.
2009;105:103-4.
Mark E Sherman M.D. Theories of Endometrial carcinogenesis: A Multidisciplinary Approach. Mod Pathol
2000;13(3):295–308
Christina M cruz the use of imaging in endometrial cancer. Harvard medical school. September 2010
Saha TK et al. the validity of transvaginal Ultrasound in measurement of endometrial thickness. A comparison of
ultrasound measurement with direct anatomical measurement BJOG 2004, dec111; 1419-24
Medscape
EDWARD M. BUCHANAN, MD, LARA CARSON WEINSTEIN, MD, and CHRISTINA HILLSON, MD, American Family Physician
Thank You