Endometrial hyperplasia

Question 1

what is the definition of endometrial hyperplasia?

Answer 1

An abnormal proliferation of glands within the endometrium, with an increase in gland:stroma ratio

Question 2

What are the different types of hyperplasia?

Answer 2

1) Simple hyperplasia - is a proliferative lesion with minimal glandular complexity and crowding with abundant stroma between glands
2) Simple hyperplasia with atypia

3) complex hyperplasia - represents a proliferative lesion with severe glandular complexity and crowding as well as minimal stroma between glands.
4) Complex hyperplasia with atypia

Cytologic atypia refers to enlarged epithelial cells that are hyperchromatic with prominent nucleoli and an increased nuclear-to-cytoplasmic ratio. Cytologic atypia is the most important prognostic factor for progression to carcinoma.

Question 3

What is the risk of malignant transformation for different types of hyperplasia?

Answer 3

• Hyperplasia without atypia has <2% risk of malignant transformation and the mean duration of progression to cancer is 10 years.
• Hyperplasia with atypia has a 23% risk of malignant transformation, with a mean duration of progression to cancer is 4 years.
• 30-50% of cases with suspected atypical hyperplasia have concurrent cancer.

Question 4

What is the incidence of hyperplasia?

Answer 4

Incidence increases with age.
In postmenopausal women presenting with AUB the incidence of all types hyperplasia is 8-15%.

Question 5

Risk factors for hyperplasia?

Answer 5

• Increasing age - peri-/postmenopausal
• High BMI
• Diabetes
• Hypertension
• Increasing age
• Nulliparity
• PCOS / anovulatory cycles
• Exogenous estrogen (e.g. unopposed HRT)
• Tamoxifen
• Endogenous estrogen (e.g.ovarian granulosa cell tumour)
• Family history: breast or endometrial cancer

Question 6

What are the treatment options for hyperplasia without atypia?

Answer 6

First line:

Conservative
- weight loss, optimise diabetic control, close monitoring
AND
Medical (needs minimum 6 months treatment)
- oral progestogens (NET/provera)
- Mirena IUS
SURVELLANCE
- Minimum 6 monthly endometrial sampling
- Consider 3 monthly if persistence
- Once 2 normal samples > 6 months apart can discharge to GP, with advice to represent if abnormal bleeding
- If BMI >35, on oral progestogen or other risk factors for progression - should continue to have annual sampling

Observational studies have shown 90–95% regression in non-atypical hyperplasias using progestogen treatment.

Second Line:

Surgery - TAH-BSO
- Suitable for women who’s family is complete AND:

• Cannot tolerate progestogen treatment
• Declines surveillance
• Has persistence of hyperplasia after 12 months of progestogens
• Has progression to hyperplasia with atypia / cancer despite progestogen treatment
• Has recurrence of hyperplasia despite previous progestogen treatment

Question 7

What are the treatment options for atypical hyperplasia?

Answer 7

1st line
- TAH-BS0

If not fit for surgery
- Full Ix to exclude co-existing endometrial cancer and ovarian cancer (risk of coexisting ovarian ca is up to 4%) - H&C, USS/MRI pelvis, CA125
then…
- LNG-IUS
- high dose oral progestogen (e.g. megestrol 80mg po bd)
- 3 monthly sampling till 2 consecutive negative samples
- 6-12 monthly sampling thereafter, until hysterectomy performed

NB. Up to 25% live birth rate after conservative management for atypical hyperplasia

Question 8

What histopathological findings are found in endometrial hyperplasia WITH atypia?

Answer 8

Hyperplasia:

• Irregular proliferation of endometrial glands
• Increased gland to stroma ratio

Atypia:

• Nuclear atypia

Question 9

Definition of endometrial hyperplasia?

Answer 9

an irregular proliferation of the endometrial glands with an increase in the glands to stroma ratio

Question 10

Risk factors for endometrial hyperplasia?

Answer 10

Occurs when unopposed oestrogen stimulates endometrial cell growth by binding to oestrogen receptors in the nuclei of endometrial cells. Immunosuppression and infection may also be involved.
• BMI>35
• Anovulation associated with perimenopause or PCOS
• Oestrogen secreting tumours eg granulosa cell tumours
• Drug induced endometrial stimulation (e.g. tamoxifen or systemic oestrogen replacement therapy)
• Diabetic/HTN
• Nulliparous
• Late menopause (>52 years)

Question 11

Risk of hyperplasia without atypia becoming cancer?

Answer 11

<5% over 20 years

Question 12

Risk of hyperplasia with atypia becoming cancer

Answer 12

8% in 4 years
27.5% in 19 years

Question 13

Probability of cancer in PMB with ET<4mm?

Answer 13

<1%

Question 14

Use of USS for estimating hyperplasia risk in premenopausal women?

Answer 14

use of USS is to detect intrauterine abnormalities as hyperplasia may still have a normal ET.

A study looking at women with PCOS found that below 7mm the likelihood of hyperplasia was very low.

Question 15

Pipelle sensitivity and specificity?

Answer 15

…

Question 16

Treatment for endometrial hyperplasia without atypia

Answer 16

Either continuous oral (not cyclical) or mirena (mirena should be first line) as it has higher regression rates, more favourable bleeding profile and fewer side effects.

Question 17

Follow up for women with endometrial hyperplasia without atypia?

Answer 17

• Follow up: Treatment for 6 months then endometrial biopsy. Two consecutive 6-monthly negative biopsies are needed prior to discharge.
• Advise women to seek medical attention again if there is any further abnormal vaginal bleeding due to risk of relapse
• Women at higher risk of relapse (e.g. BMI>35 or treated with oral progestogen) should have annual follow up

Question 18

Indications for hysterectomy for patients with endometrial hyperplasia without atypia?

Answer 18

o Progression to atypical hyperplasia occurs during follow up
o No regression after 12 months treatment
o Relapse after progestogen treatment
o Persistance of bleeding symptoms
o The woman declines medical treatment or surveillance
o Offer BSO for postmenopausal women. Premenopausal- decision to remove the ovaries needs to be individualised by BS recommended.

Question 19

Treatment for hyperplasia with atypia? (not fertility sparing)

Answer 19

• total hysterectomy due to the risk of progression to cancer and postmenopausal women should be offered BSO.

Premenopausal women should have BS, decision for oophorectomy should be individualised.

Question 20

Treatment for hyperplasia with atypia for women wishing to preserve fertility?

Answer 20

Counsel re risks of malignancy, pretreatment investigations should aim to rule out cancer (endometrial and ovarian), histology/imaging and tumour markers should be reviewed at an MDM. First line treatment is with a mirena, second with oral progestogen (megestrol 160-320mg or provera 400-600mg daily) with surveillance 6 monthly until regression, then annually till definitive surgery. Hysterectomy recommended once fertility no longer desired due to high risk of disease relapse.

Disease regression should be achieved on 2 samples 6 month apart prior to removing progesterone and attempting to conceive. Refer to fertility (May be eligible for consult if not treatment - age <40, bmi <32). Consider bariatric and dietician referral.

Question 21

Which women with PMB should be investigated?

Answer 21

• Any postmenopausal woman not on HRT with PMB
• Women on continuous combined HRT who have bleeding 6/12 after treatment
• Women on cyclical HRT who have bleeding outside of the usual withdrawal bleed
• 10% of patients will have cancer

Question 22

Common causes of PMB?

Answer 22

• Oestrogen/hormone therapy
• Atrophic vaginitis
• Uterine or cervical polyps
• Endometrial hyperplasia
• Cancer of the cervix, uterus or vagina