Endometrial CA

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

Any vaginal bleeding that occurs after 12-months period of amenorrhea that has occur due to menopause.

In Malaysia, average menopausal age are

51.7 years old

AETIOLOGY

UTERUS

Endometrial carcinoma

Endometrial hyperplasia

Uterine polyps

Senile atrophic

endometritis

Ovary

Oestrogensecreting ovarian

tumour –Granulosa Theca cell

tumor

Cervix

Cervical carcinoma

Cervical polyp

Vagina

Atrophic vaginitis

Non-gynaecology

cause

GIT-Haemorroid, sigmoid

diverticulum

GNT- UTI

Others

ITP

Iatrogenic

Hormone Replacement

Therapy

ENDOMETRIAL CARCINOMA

Endometrial polyp Cervical polyp

ATROPHIC VAGINITIS

After menopause Hormone replacement

therapy

Loss of vaginal

moisture

Loss of

labial and

vuvlvar

fullness

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:

Hypertension

Nulliparous

Gender

Age

Diabetes

RISK FACTOR

Obesity Early Menarche

Late Menopause >52 years

Polycystic Ovarian Syndrome

Functioning Ovarian Tumour

Chronic Anovulatory Genetic

Family History

Hormone Replacement Therapy

Tamoxifen

ESTROGEN

OBESITY

ENDOGENOUS ESTROGEN

Endogenous estrogen

Early Menarche

Late Menopause >52 years

Polycystic Ovarian Syndrome

Chronic Anovulatory

Functioning Ovarian Tumour

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

Prolonged unopposed estrogen

exposure

Endometrial proliferation and thickening

Endometrial hyperplasia


NON-MODIFIABLE RISK FACTOR

Non modifiable risk

factor

Genetic

Lynch Syndrome

BRACA 1 & 2

Cowden syndrome

Family historyEndometrial carcinoma

DNA mismatch repair gene

mutation

PTEN mutation - Rare autosomal dominant

familial syndrome – high risk for breast,

thyroid and endometrial carcinoma

High risk for breast, ovarian

and endometrial carcinoma

EXOGENOUS ESTROGEN

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

His

tory

ta

kin

g

age

LMP

Bleeding

Vaginal discharge

Constitutional symptoms

Obstetric hx

Gynaecology hx

Drug hx15

History Taking

16

• 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)?

• 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

History Taking

18

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


• 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

• mutations in the PTEN tumor suppressor

gene have been identified in both

endometrioid carcinoma and endometrial

hyperplasia

Pathology of

Endometrioid adenocarcinoma (Type I)

22

• generally occur a decade later than type I

carcinoma

• usually arise in the setting of endometrial atrophy

in contrast to type I

Pathology of

Serous papillary carcinoma (Type II)

23

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

Types of endometrial Ca

• 60% is pure adenocarcinoma

• Based on glandular differentiation

Grade 1 Grade 2 Grade 3

Histology

25

• Adeno-squamoid. Divided into 2:

Grade 1 Adeno-acanthoma. Squamous cell well-

differentiated

Grade 2 adeno-squamous. Poorly differentiated

squamous cell

Histology

26

• Clear cell carcinoma. Grade 3. Poor prognosis! Common

in elderly.

Histology

27

• 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

Clinical Features

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

STAGINGStage 1 Stage 2 Stage 3 Stage 4

Confine to uterine body

1a: < 50% invasion

1b: > 50% invasion

Tumour invading cervical stroma

2a: Endocervicalglandular involvement only

2b: Cervical stromainvasion

Local and/or regional spread tumour

3a: Invades serosa of uterus

3b: Invades vagina and/or parametrium

3c: Metastases to pelvic and/or para aortic nodes

Tumour invades blader ± bowel ±distant metastases

FIGO Staging of Carcinoma of the Uterus

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

TypesType of spread Explanation

Local Invasion to the myometrium –commonest spreadSpread may involve vaginal vault

Lymphatic May involve all pelvic nodes, including internal iliacs, parametrium, ovaries, and vaginaMore likely to occur if the tumour is anaplastic and uterine wall is deeply invaded

Tubal Malignant cells pass along the tubeAccount for isolated ovarian metastases

Venous Account for occasional appearance of a low vaginal metastasis

INVESTIGATIONS

INVESTIGATION

Test

Transvaginalultrasound scanning

Dilatation and curettage

Hysteroscopy

Magnetic resonance

imaging (MRI)

Endometrial biopsy Pipelle

samplingPipelle

INVESTIGATION

Test



Hysteroscopy

Magnetic resonance

imaging (MRI)


samplingPipelle

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

INVESTIGATION

Test


Dilatation and

curettage

Hysteroscopy

Magnetic resonance

imaging (MRI)


samplingPipelle

• 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

INVESTIGATION

Test



Hysteroscopy

Magnetic resonance

imaging (MRI)


samplingPipelle

• Performed in the outpatient setting or inpatient under general anaesthetic

• Allow :Direct visualization of the whole endometriumDirected biopsy to be performed

• Indications: any abnormal bleeding from the uterus can be investigated

postmenopausal bleeding

irregular menstruation, intermenstrual bleeding, and postcoital bleeding

persistent menorrhagiapersistent discharge suspected uterine malformations suspected Asherman’s syndrom

INVESTIGATION

Test



Hysteroscopy

Magnetic resonance

imaging (MRI)

Endometrial biopsy

Pipelle

• 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 Jarvis anterior vaginal wall retractor Vulsellum

Uterine sound Cervical dilator

Sponge holding forceps Curette

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 vaginalwall 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 Hegar’s dilators. Begin with the smallest dilator

and end with the largest dilator that ensures adequate dilatation

(usually 10–12 mm)

Evacuate the contents of the uterus with a large curette. Scrape the

uterus until gritty sensation felt.

Send material for histopathological examination

Pipelle’s 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 thecervix. Pipelle is then inserted into and gently passed through thecervical canal and into uterine cavity

When the sheath is in position, holding the sheath in position withone hand, with the other hand rapidly pull the piston firmly towardthe proximal end of the sheath as far as it will go.

After pulling the piston, the sheath should be continously rotated360◦ by rolling or twirling between the fingers while moving thesheath laterally, back and forth between the fundus and internal osat 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

INVESTIGATION

Test



Hysteroscopy

Magnetic resonance

imaging (MRI)

Endometrial biopsy

Pipelle

• 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

Patient’s comorbidities

Standard surgery:Total hysterectomy, bilateral sapingectomy

Performed abdominally OR laparoscopically

Pre-operative Evaluation1) 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 abscessPrevious

laparotomy

Adhesions with bowel

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(%)

I 88

II 75

III 55

IV 16

Documents

Endometrial CA