ENDOMETRIAL CARCINOMA

TRIGGER:
55 years old, nulliparous lady
come to clinic for bleeding per
vaginal for 2 weeks. She was
menopause for 3 years
duration. She had diabetes and
hypertension and was on
treatment for 2 year.

DEFINITION
POSTMENOPAUSAL BLEEDING

In Malaysia, average
menopausal age are
51.7 years old

Any vaginal bleeding that occurs

after 12-months period of
amenorrhea that has occur due to
menopause.

AETIOLOGY
UTERUS

Ovary

Endometrial
carcinoma
Endometrial
hyperplasia
Uterine
polyps
Senile
atrophic
endometritis

Oestrogen
secreting
ovarian
tumour
Granulosa
Theca cell
tumor

Cervix

Vagina

Nongynaecology
cause
GITHaemorroi
d, sigmoid
diverticulu
m

Cervical
carcinoma

Atrophic
vaginitis
Cervical
polyp

Others

ITP

Iatrogenic

GNT- UTI

Hormone
Replacement
Therapy

ENDOMETRIAL CARCINOMA

Endometrial polyp

Cervical polyp

ATROPHIC
VAGINITIS

Loss of vaginal
moisture

Loss of
labial and
vuvlvar
fullness

After menopause

Hormone replacement
therapy

DEFINITION
ENDOMETRIAL CARCINOMA
Endometrial carcinoma is types of malignancy that arise from endometrium or
lining of uterus. Encyclopedia of Cancer, Volume 1

Cancer that forms in tissues of the uterus (the small, hollow, pear-shaped organ in a
woman's pelvis in which a fetus develops). National Cancer Institute

RISK FACTORS:
Gender
Age

Diabetes
Hypertension
Nulliparous

RISK FACTOR
ESTROGEN

Obesity

Early
Menarche

Chronic
Anovulatory

Functioning
Ovarian
Tumour

Hormone
Replacement
Therapy

Tamoxifen

Late
Menopause
>52 years

Polycystic
Ovarian
Syndrome

Genetic

Family
History

OBESITY

ENDOGENOUS
ESTROGEN

Prolonged unopposed estrogen

exposure

Early
Menarche

Endometrial proliferation and thickening

Endometrial hyperplasia

Late
Menopause
>52 years
Endogenous
estrogen

Polycystic
Ovarian
Syndrome
Chronic
Anovulatory
Functioning
Ovarian
Tumour

Endometrial carcinoma

absence of ovulation infrequent irregular

prolonged menstrual period estrogen continue to
cause growth and proliferation of endometrium
endometrium thick enough to break down and
slough as menstruation

NON-MODIFIABLE
RISK FACTOR
Lynch
Syndrome
Genetic
Non
modifiable risk
factor

BRACA 1 & 2
Cowden
syndrome

Family history

Endometrial
carcinoma

DNA mismatch repair gene

mutation
High risk for breast, ovarian
and endometrial carcinoma
PTEN mutation - Rare autosomal dominant
familial syndrome high risk for breast,
thyroid and endometrial carcinoma

EXOGENOUS
ESTROGEN
Hormone
replacement
therapy

Prolonged
exposure to
estrogen

Tamoxifen

Breast cancer
treatment estrogen
antagonist in breast
but estrogen agonist
in endometrium
endometrial
hyperplasia high
risk for endometrial
carcinoma

Exogenous
estrogen

age

History taking

LMP
Bleeding
Vaginal discharge
Constitutional symptoms

Obstetric hx
Gynaecology hx
Drug hx
15

History Taking
Last menstrual period?
Age?
Bleeding:
Amount & duration of bleeding?
Is it associated with intercourse?
Any associated symptom?
Any similar previous episodes?
Any vaginal discharge:
Any features suggestive of infection?
Any constitutional symptom (LOW, LOA)?

16

History Taking
Obstetric history:
Nulliparity associated with endometrial carcinoma or ovarian
carcinoma

Gynaecology history:
Result of pap smear test

Drug history:
Usage of HRT?
On Tamoxifen therapy?
17

Physical Examination
General appearance
Pallor
Cachexia
Lymphadenopathy
Establish BMI

Abdominal examination
Uterus with normal size
Enlargement of uterus in late cases

Vaginal examination with speculum

18

Endometrial carcinoma
30% of all gynaecological malignancies
Mean age diagnosis is 54
Seen in post menopausal age group, but
may still be seen in peri-menopausal women

19

Aetiology of endometrial carcinoma

Unknown exact cause
Clear association with high levels of

circulating oestrogen in body.

20

Pathology of endometrium carcinoma

Clinicopathologic studies and molecular
analyses support the classification of
endometrial carcinoma into type I and type II.
Type I: Endometrioid adenocarcinoma
(commonest, 90%)
Type II: Serous papillary carcinoma
21

Pathology of
Endometrioid adenocarcinoma (Type I)
mutations in the PTEN tumor suppressor
gene have been identified in both
endometrioid carcinoma and endometrial
hyperplasia

22

Pathology of
Serous papillary carcinoma (Type II)
generally occur a decade later than type I
carcinoma
usually arise in the setting of endometrial atrophy
in contrast to type I

23

Types of endometrial Ca
Type 1 (80%)

Type 2 (20%)

Estrogen dependent

Non-estrogen dependent

Younger age

Elderly

Good prognosis

Poorer prognosis

Usually develops from a pre-existing

endometrial hyperplasia &
intraepithelial neoplasia

Precursor lesions rarely identified

Histological subtypes tend to be lower

grade:
-endometrioid adenocarcinoma
(grade 1 & 2)

Histological subtypes tend to be high

grade:
- endometrioid adenocarcinoma
(grade 3)
- Serous carcinoma
- clear cell carcinoma
- SCC

24

Histology
60% is pure adenocarcinoma
Based on glandular differentiation

Grade 1

Grade 2

Grade 3
25

Histology
Adeno-squamoid. Divided into 2:
Grade 1 Adeno-acanthoma. Squamous cell welldifferentiated
Grade 2 adeno-squamous. Poorly differentiated
squamous cell

26

Histology
Clear cell carcinoma. Grade 3. Poor prognosis! Common
in elderly.

27

Clinical Features
abnormal vaginal bleeding.- post-menopausal or
irregular-90% cases
Postmenopausal woman >> postmenopausal bleed
(slight and intermittent at first, then become
continuous and heavy) and watery vaginal discharge
which later become offensive.
Premenopausal woman >> intermenstrual bleeding,
blood-stained vaginal discharge, heavy menstrual
bleeding, lower abdominal pain, & dyspareunia.

Clinical Features
Loss of appetite, Loss of weight
Compression symptoms
Pap smear result showed abnormal glandular
cytology
advance cancer, these symptoms may be seen:
Evidence of fistula (uterus to bladder / rectum)
Bony metastases
Altered liver functions
Respiratory symptoms

GRADES

Grade 1:
-well differentiated <
5% solid growth
-easily recognizable
glandular patterns.

Grade 2:
-moderately
differentiated (<50%
solid growth)
-well formed glands w/
solid sheets of
malignant cells

Grade 3:
-poorly differentiated
(>50%)
-solid sheets of
malignant cells
-barely recognizable
glands

STAGING
Stage 1

Stage 2

Confine to uterine
body

Tumour invading
cervical stroma

1a: < 50% invasion

2a: Endocervical
glandular
involvement only

1b: > 50% invasion

2b: Cervical stroma

invasion

Stage 3

Stage 4

Local and/or regional Tumour invades

spread tumour
blader bowel
distant metastases
3a: Invades serosa of
uterus
3b: Invades vagina
and/or parametrium
3c: Metastases to
pelvic and/or para
aortic nodes

FIGO Staging of Carcinoma of the Uterus

Low grade tumor (stage 1a or 1b) may be offered surgery

All high-grade tumors (stage 2 and above) should have
surgery

METASTASIS
Slow to spread endometrium lack of lymphatics
Most metastases occur in adjacent structure and peritoneum
Advance cases distant metastases occur, most commonly in
lung, occasionally in liver, vertebrae or other bones and in
supraclavicular lymph nodes

Types
Type of spread

Explanation

Local

Invasion to the myometrium

commonest spread
Spread may involve vaginal vault

Lymphatic

May involve all pelvic nodes, including

internal iliacs, parametrium, ovaries, and
vagina
More likely to occur if the tumour is
anaplastic and uterine wall is deeply
invaded

Tubal

Malignant cells pass along the tube

Account for isolated ovarian metastases

Venous

Account for occasional appearance of a

low vaginal metastasis

INVESTIGATIONS

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Endometrial
biopsy Pipelle
sampling
Magnetic
resonance
imaging (MRI)

Dilatation
and curettage

Pipelle

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Endometrial
biopsy Pipelle
sampling
Magnetic
resonance
imaging (MRI)

Dilatation
and curettage

Pipelle

a) Liver function test - evidence of metastasis

b) Renal profile - ureteric obstruction / evidence
of metastasis
c) CA-125 tumour marker (advanced

endometrial cancer)
d) Chest X-ray look for lung metastasize

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Endometrial
biopsy Pipelle
sampling
Magnetic
resonance
imaging (MRI)

Dilatation
and
curettage
Pipelle

 Accurate assessment of endometrial

thickness and of the ovaries
Thickness of endometrium :
< 4mm = cancer is very unlikely
> 4mm = require hysteroscopy and biopsy

Women on tamoxifen (breast cancer)

cannot be diagnosed by using TVUS due to
thickened, irregular and cystic
endometrium (distorted endometrial
architecture)
prefer hysteroscopy and endometrial biopsy

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Endometrial
biopsy Pipelle
sampling
Magnetic
resonance
imaging (MRI)

Dilatation
and curettage

Pipelle

 Performed in the outpatient setting or inpatient

under general anaesthetic
Allow :
Direct visualization of the whole endometrium
Directed biopsy to be performed

Indications: any abnormal bleeding from the

uterus can be investigated
postmenopausal bleeding

irregular menstruation, intermenstrual bleeding, and

postcoital bleeding
persistent menorrhagia
persistent discharge
suspected uterine malformations
suspected Ashermans syndrom

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Dilatation
and curettage
Endometrial
biopsy
Pipelle
Magnetic
resonance
imaging (MRI)

 Endometrial cancer can only be diagnosed by

histological examination of a biopsy
Done in women whose ultrasound scan
reveals endometrial thickness of greater than
4 mm
Performed using an endometrial sampler :
dilatation and curettage
Pipelle

Dilatation and Curettage

Can be done under general, spinal or local anesthesia
May be done with hysteroscopy
Risks include bleeding, perforation and infection and
anesthesia complications.
Perform a bimanual pelvic examination to assess the size and
position of the uterus.

D&C Instruments

Sim's speculum

Uterine sound

Sponge holding forceps

Jarvis anterior vaginal wall retractor

Cervical dilator

Curette

Vulsellum

Dilatation and Curettage

Procedure
Explain the procedure to patient; benefits &
complications
Consent form
Anaesthesia
Lithotomy position
Empty bladder & Sterile environment

Anterior vaginal wall is retracted with Jarvis anterior vaginal

wall retractor

Gently grasp the anterior lip of the cervix with a vulsellum or

single-toothed tenaculum
Gently pass a uterine sound through the cervix to assess the length
and direction of the uterus
Use graduated Hegars dilators. Begin with the smallest dilator
and end with the largest dilator that ensures adequate dilatation
(usually 1012 mm)
Evacuate the contents of the uterus with a large curette. Scrape the
uterus until gritty sensation felt.
Send material for histopathological examination

Pipelles Sampling Method

Prepare the vagina and cervix using antiseptic

Insert speculum into vagina and open to expose the uterine cervix.
Grasp the cervix with a very fine forceps or a tanaculum.
Now, withdraw the speculum approximately 2 cm and stabilize the
cervix. Pipelle is then inserted into and gently passed through the
cervical canal and into uterine cavity
When the sheath is in position, holding the sheath in position with
one hand, with the other hand rapidly pull the piston firmly toward
the proximal end of the sheath as far as it will go.
After pulling the piston, the sheath should be continously rotated
360 by rolling or twirling between the fingers while moving the
sheath laterally, back and forth between the fundus and internal os
at least 3 or 4 times to obtain sample.

FIGURE 1. Endometrial suction

catheter.
(A) The catheter tip is inserted into
the uterus fundus or until resistance
is felt.
(B) Once the catheter is in the
uterus cavity, the internal piston is
fully withdrawn.
(C) A 360-degree twisting motion is
used as the catheter is moved
between the uterus fundus and the
internal os.

Indications and Contraindications

Indications

Contraindications

Abnormal uterine bleeding

Pregnancy

Postmenopausal bleeding

Acute pelvic inflammatory disease

Cancer screening (e.g., hereditary

nonpolyposis colorectal cancer)

Clotting disorders (coagulopathy)

Evaluation of patient with one year of

amenorrhea

Acute cervical or vaginal infections

Evaluation of infertility

Cervical cancer
Morbid obesity

Advantages

Takes only a few minutes to perform

Less bleeding
Less pain
Least expensive
Not requiring hospitalisation, anaesthesia or cervical dilatation
Low risk of perforation
High degree of sensitivity and specificity for the detection of
endometrial

Disadvantages
Procedure being uncomfortable or even
painful, especially in nulliparous women
Miss focal lesions in the uterine cavity (polyp
and sub mucous fibroid)
Inadequate sampling may be obtained,
particularly in post menopausal women

Test
Transvaginal
ultrasound
scanning

INVESTIGATION

Hysteroscopy
Dilatation
and curettage
Endometrial
biopsy
Pipelle
Magnetic
resonance
imaging (MRI)

 Function :
Give information regarding extent of disease
(stage)
Decide on the type of surgical treatment offered
to patient

Management
Surgery
Adjuvant treatment

Surgery
Extent of surgery depends on factors:
Grade of disease
MRI stage
Patients comorbidities

Standard surgery:
Total hysterectomy, bilateral sapingectomy
Performed abdominally OR laparoscopically

Pre-operative Evaluation
1) Blood test
Full blood count
Postprandial sugar
Urea and electrolyte
Liver function test
Renal function test
2) Urine for protein,sugar and pus cells
3) ECG & Chest X-ray for cardiopulmonary assessement
4) Abdominal and pelvic ultrasonography for ascites,
metastatic liver, para-aortic nodes
5) MRI/ CT imaging (optional)- to assess extrauterine spread of
disease and degree of myometrium

Stage 1
-confined to uterine body
Total abdominal hsyterectomy, bilateral
salpingo-oopherectomy (TAHBSO)
Well differentiated/ Grade 1-2 tumour
Superficially invasive (Stage 1a)

Peritoneal saline washings for cytology

ADD Post-operative radiotherapy in:

Deeply invading tumour (Stage 1b)
Increase incidence of LN involvement

Stage 2
-invade cervical stroma
Radical hysterectomy
Pelvic lymphadenoctomy + Para-aortic
node sampling
Alternative: Local and external
radiotherapy

Radical hysterectomy showing cervical

invasion of endometrial cancer
Gynaecology by Ten Teachers

Stage 3
-Local and or regional spread of tumour
Radical hysterectomy
Pelvic lymphadenectomy
Para-aortic sampling
Omentectomy
Adjuvant Radiotherapy
Local radiotherapy to vaginal vault
high dose radiotherapy, HDR

External beam radiotherapy

Stage 4
-Distant metastases
Debulking surgery
Adjuvant radiotherapy
Chemotherapy
Drugs commonly used: doxorubicin, cyclophosphamide, cisplatin
Others: adriamycin, carboplatin, 5-fluorouracil

Hormonal therapy
Adjuvant progestogen therapy

Adjuvant treatment
Postoperative radiotherapy
Aim: to reduce local recurrence rate
Chemotherapy
Aim: to combat risk of distant spread of cancer

 Indications for primary radiotherapy:

Women unfit for surgery
Women with significant medical comorbidities
Surgically inoperable disease

Those with higher risk recurrence

Patients with advanced disease for palliation
therapy

 Containdications of radiotherapy:

Presence of
pelvic mass

Pelvic abscess

Adhesions with
bowel

Previous
laparotomy

Prior pelvic
radiation

Prognosis
Overall 5 year survival rate: 80% depends on:
Age
Staging
Grading
Tumour type
Risk factor
Myometrium invasion
LN involvement

Prognosis
Adverse prognostic features for survival include:
Advanced age >70 years
High BMI
Grade 3 tumours
Papillary serous or clear cell histology
Lymphovascular space involvement
Nodal metastases
Distant metastases

Prognosis
Stage

5 years survival rate(%)

88

II

75

III

55

IV

16