Endometrial abnormalities

Question 1

What should the initial management of hyperplasia without atypia be?

Answer 1

Reversible risk factors such as obesity and the use of hormone replacement therapy (HRT) should be
identified and addressed if possible.
Observation alone with follow-up endometrial biopsies to ensure disease regression can be considered,
especially when identifiable risk factors can be reversed. However, women should be informed that
treatment with progestogens has a higher disease regression rate compared with observation alone.
Progestogen treatment is indicated in women who fail to regress following observation alone and in
symptomatic women with abnormal uterine bleeding.

Question 2

What are the risks of hyperplasia without atypia?

Answer 2

The risk of endometrial hyperplasia without atypia progressing to endometrial cancer is less than 5% over 20 years and that the majority of cases of endometrial
hyperplasia without atypia will regress spontaneously during follow-up.

Question 3

What should the first-line medical treatment of hyperplasia without atypia be?

Answer 3

Both continuous oral and local intrauterine (levonorgestrel-releasing intrauterine system [LNG-IUS])
progestogens are effective in achieving regression of endometrial hyperplasia without atypia.
The LNG-IUS should be the first-line medical treatment because compared with oral progestogens it
has a higher disease regression rate with a more favourable bleeding profile and it is associated with
fewer adverse effects.
Continuous progestogens 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 without atypia compared with continuous oral progestogens orthe LNG-IUS.

Question 4

What should the duration of treatment and follow-up of hyperplasia without atypia be?

Answer 4

Treatment with oral progestogens or the LNG-IUS should be for a minimum of 6 /12.
If fertility is not desired, women should be encouraged to retain the LNG-IUS for up to 5 years as this reduces the risk ofrelapse.
Endometrial surveillance is recommended at a minimum of 6-monthly intervals, although review
schedules should be individualised and responsive to changes in a woman’s clinical condition.
At least two consecutive 6-monthly negative biopsies should be obtained prior to discharge.
Women should be advised to seek a further referral if abnormal vaginal bleeding recurs after
completion of treatment because this may indicate disease relapse.
In women at higher risk of relapse, such as women with a body mass index (BMI) of 35 or greater or
those treated with oral progestogens, 6-monthly endometrial biopsies are recommended. Once two
consecutive negative endometrial biopsies have been obtained then long-term follow-up should be
considered with annual endometrial biopsies.

Question 5

When is surgical management appropriate for women with endometrial hyperplasia without atypia?

Answer 5

Hysterectomy should not be considered as a first-line treatmentfor hyperplasia without atypia.
Hysterectomy is indicated in women not wanting to preserve their fertility when
(i) progression to atypical hyperplasia occurs during follow-up, or
(ii) there is no histological regression of hyperplasia
despite 12 months of treatment, or
(iii) there is relapse of endometrial hyperplasia after completing progestogen treatment, or
(iv) there is persistence of bleeding symptoms, or
(v) the woman declines to undergo endometrial surveillance or comply with medical treatment.

Question 6

For endometrial hyperplasia without atypia who needs surgery what approach?

Answer 6

Postmenopausal women requiring surgical management for endometrial hyperplasia without atypia should be offered a bilateral salpingo-oophorectomy together with the total hysterectomy.
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.
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.

Question 7

How should atypical hyperplasia be managed?

Answer 7

Women with atypical hyperplasia should undergo a total hysterectomy because of the risk of underlying malignancy or progression to cancer.

Question 8

For endometrial hyperplasia with atypia who needs surgery what approach?

Answer 8

Postmenopausal women with atypical hyperplasia should be offered bilateral salpingo-oophorectomy
together with the total hysterectomy.
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

Question 9

How should women with atypical hyperplasia who wish to preserve their fertility or who are not suitable for surgery be managed?

Answer 9

Women wishing to retain theirfertility 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.
Histology, imaging and tumour marker results should be reviewed in a multidisciplinary meeting and
a plan for management and ongoing endometrial surveillance formulated.
First-line treatment with the LNG-IUS should be recommended, with oral progestogens as a
second-best alternative (see section 7.2).
Once fertility is no longer required, hysterectomy should be offered in view of the high risk of disease
relapse.

Question 10

How should women with atypical hyperplasia not undergoing hysterectomy be followed up?

Answer 10

Routine endometrial surveillance should include endometrial biopsy. Review schedules should be
individualised and be responsive to changes in a woman’s clinical condition. Review intervals should
be every 3 months until two consecutive negative biopsies are obtained.
In asymptomatic women with a uterus and evidence of histological disease regression, based upon a
minimum of two consecutive negative endometrial biopsies, long-term follow-up with endometrial
biopsy every 6–12 months is recommended until a hysterectomy is performed.

Question 11

How should endometrial hyperplasia be managed in women wishing to conceive?

Answer 11

Disease regression should be achieved on at least one endometrial sample before women attempt to
conceive.
Women with endometrial hyperplasia who wish to conceive should be referred to a fertility specialist
to discuss the options for attempting conception, further assessment and appropriate treatment.
Assisted reproduction may be considered as the live birth rate is higher and it may prevent relapse
compared with women who attempt natural conception.
Prior to assisted reproduction, regression of endometrial hyperplasia should be achieved as this is
associated with higher implantation and clinical pregnancy rates.

Question 12

HRT and endometrial hyperplasia

Answer 12

Systemic estrogen-only HRT should not be used in women with a uterus.
All women taking HRT should be encouraged to report any unscheduled vaginal bleeding promptly.
Women with endometrial hyperplasia taking a sequential HRT preparation who wish to continue HRT
should be advised to change to continuous progestogen intake using the LNG-IUS or a continuous
combinedHRT preparation. Subsequent management should be as described in the preceding sections
of the guideline.
Women with endometrial hyperplasia taking a continuous combined preparation who wish to continue
HRT should have their need to continueHRT reviewed. Discuss the limitations ofthe available evidence
regarding the optimal progestogen regimen in this context. Consider using the LNG-IUS as a source of
progestogen replacement. Subsequent management should be as described in the preceding sections
of the guideline.

Question 13

How should endometrial hyperplasia be managed in women on adjuvant treatment for breast cancer?

Answer 13

Women taking tamoxifen should be informed about the increased risks of developing endometrial
hyperplasia and cancer. They should be encouraged to report any abnormal vaginal bleeding or
discharge promptly.
Women taking aromatase inhibitors (such as anastrozole, exemestane and letrozole) should be
informed that these medications are not known to increase the risk of endometrial hyperplasia and
cancer.

Question 14

Should women on tamoxifen be treated with prophylactic progestogen therapy?

Answer 14

There is evidence that the LNG-IUS prevents polyp formation and that it reduces the incidence of
endometrial hyperplasia in women on tamoxifen. The effect ofthe LNG-IUS on breast cancerrecurrence
risk remains uncertain so its routine use cannot be recommended.

Question 15

How should women who develop endometrial hyperplasia while on tamoxifen treatment for breast
cancer be managed?

Answer 15

There is evidence that the LNG-IUS prevents polyp formation and that it reduces the incidence of
endometrial hyperplasia in women on tamoxifen. The effect ofthe LNG-IUS on breast cancerrecurrence
risk remains uncertain so its routine use cannot be recommended.

Question 16

How should women who develop endometrial hyperplasia while on tamoxifen treatment for breast
cancer be managed?

Answer 16

The need fortamoxifen should be reassessed and management should be according to the histological
classification of endometrial hyperplasia and in conjunction with the woman’s oncologist.

Question 17

How should endometrial hyperplasia confined to an endometrial polyp be managed?

Answer 17

Complete removal of the uterine polyp(s) is recommended and an endometrial biopsy should be
obtained to sample the background endometrium.
Subsequent management should be according to the histological classification of endometrial
hyperplasia

Question 18

What is tamoxifen used for

Answer 18

Endocrine treatment of choice for selected patients with breast cancer
+
Preventative role in healthy women at increased risk of developing breast cancer.

Question 19

How does it work ?

Answer 19

Estrogen receptor modulator
Inhibits proliferation of breast cancer by competitive antagonism at the estrogen receptor
It is a partial agonist on other tissues including the vagina and uterus

Question 20

Tamoxifen SEs on the female genital tract:

Answer 20

• Stimulation of endometriosis, with worsening of symptoms in some patients. There has been one case report of an endometrioid carcinoma arising from an ovarian endometriotic focus.
• Stimulation of the growth of benign fibroids.
• An increased incidence of benign endometrial polyps, proliferation and hyperplasia.

• Population based data suggest an apparent small increase in the risk of uterine sarcoma with Tamoxifen use.

Question 21

What is the risk of endometrial cancer in woman taking tamoxifen ?

Answer 21

• The cumulative risk of endometrial cancer with Tamoxifen use is 1.6% at five years and 3.1% if used for 5-14 yrs.
• The risk of developing endometrial cancer in patients on Tamoxifen prophylaxis is only observed in post-menopausal women (RR = 4.01). (NOT premenopausal woman)
• Patients that have an endometrial lesion detected prior to commencing Tamoxifen have a statistically significant higher risk of developing atypical lesions at two years compared to patients that did not have a pre-existing endometrial lesion.
• The stage and grade of uterine endometrioid adenocarcinoma found in women on standard doses of Tamoxifen is comparable to those tumours found in women not taking Tamoxifen.

Question 22

What is the effect of the mirena on the endometrium?

Answer 22

A 2009 Cochrane review found that the LNG-IUS reduced the incidence of new endometrial polyps in women on tamoxifen for breast cancer over a 1-year period (Peto OR 0.14, 95% CI 0.03–0.61).
There was no clear evidence that the LNG-IUS prevented endometrial hyperplasia or cancer in these women.
An updated subgroup analysis has confirmed that endometrial hyperplasia is reduced as well as endometrial polyp formation

Question 23

Lymph drainage of the uterine corpus

Answer 23

The lymphatic system of the corpus uteri is formed by three main lymphatic trunks: utero‐ovarian (infundibulopelvic), parametrial, and presacral.

These drain into the
They collectively drain into the hypogastric (also known as internal iliac), external iliac, common iliac, presacral, and para‐aortic nodes.

Question 24

Where does endometrial ca metastasis to?

Answer 24

The vagina, ovaries, and lungs are the most common metastatic sites.

Question 25

What are the grades of endometrial cancer

Answer 25

GX: Grade cannot be assessed.

G1: Well differentiated.
less than 5% of a nonsquamous or nonmorular solid growth pattern.

G2: Moderately differentiated.
6%–50% of a nonsquamous or nonmorular solid growth pattern.

G3: Poorly or undifferentiated.
greater than 50% of a nonsquamous or nonmorular solid growth pattern.

Nuclear atypia (prominent nucleoli and pleomorphism) that Is inappropriate for the architectural grade raises the grade by 1

Question 26

What is type 1 vs type 2 endometrial cancer

Answer 26

Type 1
Endometrioid type grade 1 and 2
Endometrioid carcinoma: adenocarcinoma; adenocarcinoma‐variants (with squamous differentiation; secretory variant; villoglandular variant; and ciliated cell variant).

Type 2
Grade 3 endometrioid
Serous / clear cell, mucinous, undifferentiated, neuroendocrine tuors, mixed carcinoma

Question 27

What is the difference in presentation and epidemiology of type 1v s 2

Answer 27

Type 1
Young 
Obese 
Estrogen related 
Low grade 
Perinenopausal 
Excellent overall prognosis 
Oncogene / TSG mutation PTEN, MMR, KRAS, B Catenin  

Type 2
Older 
Thinner 
Black >white 
Hyperplasia not a precursor  
Not related to estrogen 
Aggressive 
Oncogene P53, Her-2-neu 
Potential genetic basis – lynch, familial trend  
Less hormone sensitive

Question 28

What is
Stage 1 endometrial cancer
1A
1B

Answer 28

1- confined to the uterus
A- no or less then 1/2 myometrial invasion

B - Invasion equal to or more than half of the myometrium

Question 29

What is

Stage 2 endometrial cancer

Answer 29

Tumor invades the cervical stroma, but not beyond

Question 30

What is 
Stage 3 endometrial cancer
3A
3B
3C 1,2

Answer 30

Stage 3Local and/or regional spread of the tumor
3A
Tumor invades the serosa of the corpus uteri and/or adnexaec
3B
Vaginal involvement and/or parametrial involvement
3C
Metastases to pelvic and/or para‐aortic lymph nodes
3C1
Positive pelvic nodes
3C2
Positive para‐aortic nodes with or without positive pelvic lymph nodes

Question 31

Stage 4 endometrial cancer
4A
4B

Answer 31

Invading bladder. bowel or distant mets

4A - bladder or bowel
4B distant mets including intra abdominal or inguinal nodes

Question 32

TNM classification of endometrial cancer

Answer 32

N - nodes
NX - unable to be assessed
N0 - no regional node mets
N1 - mets to pelvic nodes
N2 - met to para aoritc nodes 

MX - cant assess
M0 no distant mets
M1 mets - inguinal lymph nodes or intraperitoneal disease

Question 33

who gets surgical lymph dissection?

Answer 33

1b and above
High risk eg clear cell and serous histology
Grade 3
AT MINIMUM all pelvic nodes and any enlarged para aortic nodes

Question 34

Screening for lynch 2 syndrome?

How? and what final intervention

Answer 34

Screening from 35 with pipelle and TV USS annually

TAH BSO for risk of endometrial and ovarian cancer shuld be offered by 40

Question 35

4 histopathological features to determine high risk disease

Answer 35

tumor grade 3 (poorly differentiated)
LVSI
Non endometrioid histology
Cervical stromal involvement

Question 36

how to perform surgical staging

Answer 36

Steps
opening of the abdomen with a vertical midline incision
peritoneal washings taken immediately from the pelvis and abdomen
Followed by careful exploration of the intra‐abdominal contents.
The omentum, liver, peritoneal cul‐de‐sac, and adnexal surfaces should be examined and palpated for any possible metastases
Then careful palpation for suspicious or enlarged nodes in the aortic and pelvic areas.
However, laparoscopic procedures have increasingly been introduced as standard, especially for early stage disease, as these have been proven safe and reduce acute treatment‐related complications