Endometrial hyperplasia and endometrial cancer

Prof. dr Esraa AL-Maini

2019-2020
5 TH CLASS

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Objectives:

1- Recognize the different types of ca endometrium ,define the stages

of endometrial cancer name the mode of spread

2-interpret the risk factors of endometrial hyperplasia and

endometrial ca , and factors decrease the incidence

3- Execute the clinical features of endo ca ,interpret the clinical

finding at examination and summarize the result of investigation

4- implement the classification to clinical scenario to determine the

stage , critique the management of each stage

5-classify types of endometrial hyperplasia

6-summerize the clinical manifestation of women with endometrial

hyperplesia and endometrial ca

7-execute the indication for evaluation of endometrium

8-modify the management according to types and fertility wishes and

age

9- critique different types of clinical scenario.

In premenopausal women :
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Endometrial thickness in normal endometrial vary according to day of
cycle ;≤ 4 mm on day 4 of the menstrual cycle ≤ 8 mm by day 8.

persistent endometrial thickness, independent of cycle day,

measuring =>12 mm should be further evaluated especially for
women those with risk factors for endometrial carcinoma

Etiology:
A. Endogenous estrogen. The most common cause of endogenous
unopposed estrogen is chronic anovulation. Chronic anovulation is
associated with the polycystic ovary syndrome(PCOS) and the
perimenopausal period. Excessive estradiol from an ovarian tumor
(eg, granulosa cell tumor) may also cause endometrial hyperplasia,
obese women have high levels of endogenous estrogen resulting from
conversion of androstenedione to estrone and of androgens to
estradiol.

B. Exogenous estrogen.

Classification endometrial hyperplasia

The World Health Organization classification of endometrial hyperplasia
is based upon two factors:

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1. Simple or complex glandular/stromal architectural pattern

2. The presence or absence of nuclear atypia

Endometrial carcinoma is more than 10-fold more likely in atypical

hyperplasia (simple or complex).

Cancer occurs after a diagnosis of simple, complex, simple atypical, and

complex atypical hyperplasia in 1, 3, 8, and 29% of cases, respectively.

Risk factors
1-Increasing age 2-Unopposed estrogen therapy

3-Late menopause (after age 55) 4-Nulliparity

5-Polycystic ovary syndrome (Chronic anovulation)

6-Obesity 7-Diabetes

8-Hereditary nonpolyposis colorectal cancer 9-Tamoxifen

10-Early menarche 11-Estrogen secreting tumor

12-Family history of endometrial, ovarian, breast, or colon cancer

Clinical manifestation;
Endometrial hyperplasia should be suspected;

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 1- Women with heavy, prolonged, frequent (ie, less than 21
days).

2- Irregular uterine bleeding.

Abnormal uterine bleeding in perimenopausal or postmenopausal

women is the most common clinical symptom of endometrial
neoplasia, although such bleeding is usually (80%) due to a benign
condition.

Diagnostic and surveillance methods for endometrial

hyperplesia
1-Transvaginal sonography; may have a role in diagnosing
endometrial hyperplasia in pre- and postmenopausal women
2-Endometrial biopsy :diagnosis of endometrial hyperplasia
requires histological examination of the endometrial tissue.
1-Office biopsy(out patients)

2-D/C biopsy.

3-Hysteroscopic guided biopsy

A- Indication for evaluation of the endometrium

1-Abnormal -uterine bleeding with risk factors (eg, chronic anovulation,
obesity, tamoxifen)
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2-Failure to respond to medical treatment for abnormal uterine
bleeding

3-Unopposed estrogen replacement therapy

4- Asymptomatic women with benign appearing endometrial cells

,presence of endometrial cells on Pap smear if they are at increased risk
of endometrial cancer

5-Women with hereditary nonpolyposis colorectal cancer

B. Indications for additional diagnostic evaluation

1-Endometrial hyperplasia with atypia is diagnosed by office biopsy,
further evaluation is needed to exclude a coexistent endometrial
adenocarcinoma, which is present in 25%. Dilation and curettage (D&C)
can be performed to rule out endometrial cancer.

2. Non diagnostic office biopsy. Endometrial hyperplasia/cancer needs

to be excluded in women with a non diagnostic office biopsy.

Dilatation and curettage or hysteroscopy with directed biopsy is

required.

3. Persistent bleeding. Endometrial hyperplasia/cancer needs to be

excluded if abnormal uterine bleeding persists after a benign
endometrial biopsy or treatment of endometrial pathology.

4. Postmenopausal women.

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Treatment:
Endometrial hyperplasia without atypia is treated in order to control
abnormal uterine bleeding and to prevent progression to cancer,
although this risk is very low below 5%over 20 years.

Atypical endometrial hyperplasia is treated for the same reasons,

except the risk of a subsequent diagnosis of endometrial cancer is much
higher (25 - 50%).

Management of hyperplasia without atypia

1- Observation alone The risk of endometrial hyperplasia
without atypia progressing to endometrial cancer is less than
5% over 20 years .
The majority of cases of endometrial hyperplasia without atypia
will regress spontaneously during follow-up.
So observation alone with follow-up endometrial biopsies to
ensure disease regression can be considered, especially when
identifiable risk factors such as obesity and the use of hormone
replacement therapy (HRT) can be reversed.
2- Treatment with progestogens has a higher disease
regression rate compared with observation alone.

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Progestogen treatment is indicated :
1-In women who fail to regress following observation alone
2- In symptomatic women with abnormal uterine bleeding.
Types of progesterone;
1- Local progesterone (levonorgestrel-releasing intrauterine
system [LNG-IUS]) should be the first-line medical treatment
because compared with oral progestogens:

1- It has a higher disease regression rate

2- More favourable bleeding profile
3- It is associated with fewer adverse effects.
2-Continuous oral progesterone should be used
(medroxyprogesterone 10–20 mg/day or norethisterone 10–15
mg/day) for women who decline the LNG-IUS.
Cyclical progestogens should not be used because they are less
effective in inducing regression of endometrial hyperplasia.

The duration of treatment and follow-up of hyperplasia

without atypia
- Treatment with oral progestogens or the LNG-IUS should be
for a minimum of 6 months in order to induce histological

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regression ,women should be encouraged to retain the LNG-IUS
for 5 YEARS this reduces the risk of relapse
1- If adverse effects are tolerable
2- fertility is not desired
3-If it alleviates abnormal uterine bleeding symptoms.
FOLLOW UP ;
-Endometrial surveillance with outpatient endometrial biopsy is
recommended after a diagnosis of hyperplasia without atypia
should be arranged at a minimum of 6-monthly intervals.
-At least two consecutive 6-monthly negative biopsies should
be obtained .
-Women should be advised to seek a further advice if abnormal
vaginal bleeding recurs after completion of treatment because
this may indicate disease relapse 6-monthly and endometrial
biopsies are recommended.
In women at higher risk of relapse;
-As body mass index (BMI) of 35 or greater
-Those treated with oral progestogens
Once two consecutive negative endometrial biopsies have
been obtained then long-term follow-up should be considered
with annual endometrial biopsies.

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3-Surgical management for women with endometrial
hyperplasia without atypia
Hysterectomy should not be considered as a first-line
treatment for hyperplasia without atypia because progestogen
therapy induces histological and symptomatic remission in the
majority of women and avoids the morbidity associated with
major surgery.
Hysterectomy is indicated in women not wanting to preserve
their fertility when
1-Progression to atypical hyperplasia occurs during follow-up,
2- There is no histological regression of hyperplasia despite 12
months of treatment
3- There is relapse of endometrial hyperplasia after completing
progestogen treatment
4- There is persistence of bleeding symptoms
5-The woman declines to undergo endometrial surveillance or
comply with medical treatment
Types of surgery

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1- Postmenopausal women requiring surgical management for
endometrial hyperplasia without atypia should be offered a
bilateral salpingo-oophorectomy together with the total
hysterectomy.
2-For premenopausal women, the decision to remove the
ovaries should be individualised; however, bilateral
salpingectomy should be considered as this may reduce the risk
of a future ovarian malignancy.

3- A laparoscopic approach is preferable to an abdominal

approach as it is associated with a shorter hospital stay, less
postoperative pain and quicker recovery.
4- Endometrial ablation is not recommended for the treatment
of endometrial hyperplasia because complete and persistent
endometrial destruction cannot be ensured and intrauterine
adhesion formation may preclude future endometrial
histological surveillance.

Management of atypical hyperplasia

A- Women with atypical hyperplasia should undergo a

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Total Hysterectomy because of
- The risk of underlying malignancy
- Progression to cancer.
A laparoscopic approach to total hysterectomy is preferable to
an abdominal approach as it is associated with a shorter
hospital stay, less postoperative pain and quicker recovery.
- Postmenopausal should be offered bilateral salpingo-
oophorectomy together with the total hysterectomy.
-premenopausal women, the decision to remove the ovaries
should be individualised; however, bilateral salpingectomy
should be considered as this may reduce the risk of a future
ovarian malignancy.
Endometrial ablation is not recommended because complete
and persistent endometrial destruction cannot be ensured and
intrauterine adhesion formation may preclude endometrial
histological surveillance.

B-Women with atypical hyperplasia who wish to preserve

their fertility or who are not suitable for surgery

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Women wishing to retain their fertility should be counselled
about the risks of underlying malignancy and subsequent
progression to endometrial cancer.
Pretreatment investigations should aim to rule out invasive
endometrial cancer or co-existing ovarian cancer BY TVUS and
endometrial biopsy
First-line treatment with the LNG-IUS should be recommended,
with oral progestogens as a second-best alternative
Once fertility is no longer required, hysterectomy should be
offered because high risk of disease relapse.
followed up
TVUS and endometrial biopsy : at 3 months interval until two
consecutive negative biopsies are obtained. Until minimum of
two consecutive negative endometrial biopsies and
asymptomatic women long-term follow-up with endometrial
biopsy every 6–12 months is recommended until a
hysterectomy is performed.
In women wishing to conceive
Disease regression should be achieved on at least one
endometrial sample before women attempt to conceive.
Assisted reproduction may be considered as the live birth rate
is higher and it may prevent relapse.

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HRT and endometrial hyperplasia
1- Systemic estrogen-only HRT should not be used in women
with a uterus.
2- All women taking HRT should be encouraged to report any
unscheduled vaginal bleeding promptly.
3- advised to change to continuous progestogen intake using
the LNG-IUS or a continuous combined HRT preparation.

Reverences :Gyn by ten teachers 20 edition

RCOG- Guid line

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