Endometrial Hyperplasias and polyps

Dr. wendwesen
 Endometrial Hyperplasias

Definition

“Endometrial hyperplasia is a histological

diagnosis characterized by proliferation of
endometrial glands resulting in a greater
gland-to-stroma ratio than observed in normal
endometrium“.
 Endometrial hyperplasia
• The proliferating glands in endometrial hyperplasia vary in
size and shape and may show cytological atypia.
• Endometrial hyperplasia may progress to or coexist with
endometrial cancer.
• Endometrial hyperplasia results from chronic estrogen
stimulation unopposed by the counterbalancing effects of
progesterone.
 Classification of endometrial hyperplasia

• The World Health Organization classification of endometrial

hyperplasia is based upon two factors:
– The glandular/stromal architectural pattern, which is
either simple or complex
– The presence or absence of nuclear atypia
• The presence of nuclear atypia is the most worrisome finding.
 Endometrial Hyperplasias

• WHO classification subdivides endometrial hyperplasia into

four categories:

 Typical hyperplasias (without cytological atypia)

1. Simple hyperplasia
2. Complex hyperplasia (architectural alterations)

 Atypical hyperplasia (with cytological atypias)

3. Simple atypical hyperplasia
4. Complex atypical (adenomatous) hyperplasia (with
architectural and cytological atypias)
 Simple versus complex
• In simple hyperplasia, the glands are cystically dilated.
• Complex hyperplasia consists of endometrial glands that are
back-to-back and the intervening stroma is minimal.
– The gland-to-stroma ratio is higher in complex compared
to simple hyperplasia.
 Atypia
• Simple atypical hyperplasia is characterized by atypical cells
lining glands that are separated by significant amounts of
normal stroma.
• Complex atypical hyperplasia consists of back-to-back
crowding of glands lined by atypical cells.
 WHO classification
• The WHO classification system is useful, because it correlates
well with the risk of developing malignancy.
• Women with simple hyperplasia without atypia are least likely
to develop endometrial carcinoma, whereas women with
complex hyperplasia with atypia are most likely to develop
carcinoma.
 Endometrial Hyperplasias

 Hyperplasia and risk of developing cancer.

 The time course from a diagnosis of endometrial hyperplasia to cancer is not
well established.
 The average time to diagnosis of cancer was six years in women with all
types of endometrial hyperplasia.

Type of hyperplasia Cancer Risk

____________________________________________
- Simple hyperplasia 1%
- Complex hyperplasia without atypia 3%
- Simple atypical hyperplasia 8%
- Complex atypical hyperplasia 30 %

____________________________________________
 RISK FACTORS
• The risk factors for endometrial hyperplasia are the same as
those for endometrial cancer.
• Exposure of the endometrium to continuous estrogen
unopposed by progesterone can lead to endometrial
hyperplasia.
• The estrogen source can be endogenous or exogenous.
 Endogenous estrogen
• The most common source of endogenous unopposed
estrogen is chronic anovulation.
– Chronic anovulation is a feature of both the PCOS and the
menopausal transition.
• Secretion of excessive estradiol from an ovarian tumor (eg,
granulosa cell tumor) may also result in endometrial
hyperplasia.
• Obese women have high levels of endogenous estrogen due
to the conversion of androstenedione to estrone and the
aromatization of androgens to estradiol, both of which occur
in peripheral adipose tissue.
 Exogenous estrogen

• Exogenous estrogen use unopposed by a progestin as

hormone replacement therapy (HRT) during menopause
increases the risk of endometrial hyperplasia.
• Estrogen therapy for postmenopausal women with a uterus
should include a progestin to minimize the risk of endometrial
hyperplasia.
 Source of estrogen
• Diagnostic evaluation for the source of estrogen in pre- or
peri-menopausal women with endometrial hyperplasia is
unnecessary.
• Clinical concern is greatest when endometrial hyperplasia is
diagnosed in a postmenopausal woman in the absence of
postmenopausal hormone therapy or obesity.
• Postmenopausal development of endometrial hyperplasia in
the absence hormone therapy or obesity requires further
evaluation to exclude the presence of ovarian estrogen
producing tumors.
 Clinical manifestations

• The incidence of endometrial hyperplasia without and

with atypia peaks in the early 50s and early 60s,
respectively .
• The diagnosis of endometrial hyperplasia should be
suspected in women with heavy, prolonged, frequent , or
irregular uterine bleeding.
• Irregular uterine bleeding in women in the menopausal
transition, or any bleeding in postmenopausal women, is
the most common clinical symptom of endometrial
neoplasia and it requires further evaluation.
 DIAGNOSTIC EVALUATION
• Endometrial hyperplasia is a pathologic diagnosis and,
therefore, cannot be made without an endometrial tissue
sample.
• An endometrial biopsy should be performed in all women
with abnormal uterine bleeding in whom endometrial
hyperplasia or carcinoma is a possibility.
 Indications for endometrial biopsy
• Over age 40 years with AUB.
• Under age 40 years with AUB and risk factors (eg, chronic anovulation,
obesity, tamoxifen use , family history of
endoemtrial/ovarian/breast/colon cancer).
• Failure to respond to medical treatment of AUB.
• Women with uterus in situ receiving unopposed estrogen replacement
therapy.
• Presence of atypical glandular cells on cervical cytology
• Presence of endometrial cells on cervical cytology in a woman ≥40 years
of age
• Women with HNPCC ( Lynch 2 syndrome).
 Endometrial Hyperplasias

 Diagnosis

- Highly built-up endometium in sonography.

- Fractional curettage of endocervix and uterine cavity.
- Diagnosis depends exclusively on the histological pattern.
 Endometrial Hyperplasias
 Hysteroscopy
 Hysteroscopy delivers information on the uterine cavity, the endometrium and the location
of tumors (polyps, carcinoma).
 Hysteroscopy carries a theoretical risk of spreading endometrial cancer cells into the
peritoneal cavity if endometrial cancer is present.
 A final diagnosis is only possible through fractional curettage and histology.

Simple, glandular-cystic Focal hyperplasia of the

hyperplasia endometrium
 TREATMENT
• The purpose of treating simple or complex
endometrial hyperplasia without atypia is:
– to control AUB,
– to prevent progression to cancer, although this risk is
very low.
• The purpose of treating Atypical endometrial
hyperplasia is:
– to prevent progression to cancer due to the significant
risk of endometrial cancer.
– Treatment recommendations typically include surgery.
 Treatment options
• Different treatment options depending upon the presence or
absence of atypia and the menopausal status of the patient.
• Treatment options:
– Medical : progestin, Gonadotropin-releasing hormone (GnRH) analogs.
– Surgical: Hysteroscopic resection of endometrial hyperplasia,
Hysterectomy.
 Progestins
• Progestins are an effective treatment of endometrial
hyperplasia .
• Progestins reverse endometrial hyperplasia and results in
stromal decidualization and subsequent thinning of the
endometrium.
• Progestin exposure also activates hydroxylase enzymes to
convert estradiol to its less active metabolite estrone.
• The response rate to progestins is highest in women without
atypia and with therapy of at least 12 to 14 days per month.
 Premenopausal women

• Endometrial hyperplasia with no atypia:

– A course of treatment with progestins (MPA 10 mg daily for 12 to 14
days each month for three to six months) with follow-up sampling to
document regression.
– Insertion of a levonorgestrel containing IUD is also effective
– Ovulation induction will result in formation of a corpus luteum and
exposure to progestins and may be another option for younger
women with endometrial hyperplasia without atypia who desire
pregnancy.
– Oral contraceptives can also be used especially if progestins alone are
poorly tolerated.
 Premenopausal women

• Endometrial hyperplasia with atypia:

– If the patient desires to maintain fertility, treatment with
progestins is initiated.
– A repeat endometrial biopsy should be performed in three
months and hysterectomy is recommended for treatment
failures.
– Hysterectomy is the treatment of choice for women who are not
planning future pregnancy or who are unwilling or unable to
comply with medical therapy and follow-up endometrial
sampling.
 Postmenopausal women
• Endometrial hyperplasia with atypia is preferably treated with
hysterectomy in Postmenopausal women.
Endometrial polyps
 Endometrial polyps
• Endometrial polyps are localized hyperplastic overgrowths of
endometrial glands and stroma around a vascular core that
form a sessile or pedunculated projection from the surface of
the endometrium.
• Single or multiple polyps can occur that range from a few
millimeters to several centimeters in size.
 Risk factors
• Endometrial polyps are rare among women younger than 20
years of age.
• The incidence of endometrial polyps rises steadily with
increasing age, peaks in the fifth decade of life, and gradually
declines after menopause.
• Risk factor for the development of endometrial polyps;
• Tamoxifen use, women with Lynch syndrome
 Clinical features
• Endometrial polyps are responsible for approximately one-
fourth of cases of abnormal genital bleeding in both
premenopausal and postmenopausal women.
• Many polyps are asymptomatic .
• Metrorrhagia (ie, irregular bleeding) including spotting is the
most frequent symptom in women with endometrial polyps,
occurring in about one-half of symptomatic cases.
• Less frequent symptoms include menorrhagia, prolapse
through the cervical os, and breakthrough bleeding during
hormonal therapy, infertility, miscarriage.
 DIAGNOSIS
• Endometrial polyps are diagnosed by microscopic examination
of a specimen obtained after curettage, endometrial biopsy,
or hysterectomy.
• Excision permits both diagnosis and cure of these lesions.
• Neither ultrasonography nor hysteroscopy can reliably
distinguish between benign and malignant polyps.
 Clinical course of endometrial polyps

• Regression— Polyps larger than 1 cm are less likely to

regress.
• Recurrence— In rare cases, endometrial polyps continue
to recur multiple times after removal.
• Malignancy — The great majority of endometrial polyps
are benign, but malignancy occurs in some women.
– Endometrial polyps are likely to be malignant if:
• It occurs in postmenopausal compared with premenopausal
women.
• It is associated with bleeding as compared to those without
bleeding.
 Treatment
• Polypectomy results in improvement of symptoms.
• Methods of polypectomy:
– hysteroscopically guided removal with grasping forceps,
– Curettage.
 Asymptomatic polyps
• In asymptomatic women, removal of polyps of any size is
recommended in those with risk factors for endometrial
hyperplasia or carcinoma.
• In asymptomatic women without risk factors, removal of
polyp is recomended when:
– the polyps are multiple ,
– a single polyp exceeding 2 cm in premenopausal women.
– a single polyp exceeding 1 cm in postmenopausal women.
• In the absence of risk factors for endometrial cancer,
asymptomatic polyps of ≤2 cm in premenopausal women are
likely to regress so it can be managed expectantly.