This document discusses pre-malignant lesions of the endometrium, including endometrial hyperplasia and endometrial adenocarcinoma. It defines endometrial hyperplasia as excessive proliferation of endometrial cells that is non-cancerous. Unopposed estrogen exposure increases the risk of developing hyperplasia. Hyperplasia can progress to cancer, with atypical forms having higher risk. Diagnosis involves imaging and biopsy. Treatment options depend on the type of hyperplasia but aim to reduce estrogen levels using progesterone.

1. Pre-malignant
lesions of
endometrium
Dr Ankur shah

2. Endometrial Hyperplasia
• Endometrial hyperplasia is a condition of
excessive proliferation of the cells of the
endometrium-Endometrial glands & surrounding
tissue (Stroma)
• Endometrial hyperplasia is a non-cancerous
condition
• May involve part or all of the endometrium

3. Endometrial Adenocarcinoma
Epidemiology
• Most frequently between the ages of 55
and 65
• Uncommon under 40 years of age

4. Pathogenesis
Hyperplasia usually develops in the presence of continuous
estrogen stimulation unopposed by progesterone.
(PCOS or Perimenopause)
• The female hormones—estrogen and progesterone—
control the changes in the uterine lining.
• Estrogen builds up the uterine lining.
• Progesterone maintains and controls this growth.
• Estrogen without enough progesterone may cause the
lining of the uterus to thicken.

5. Risksfor developingEndometrialHyperplasia
• Estrogen replacement therapy -Take estrogen without
progesterone to replace the estrogen their body is no longer
making and to relieve symptoms of menopause
• Polycystic ovary syndrome- women are anovulatory and have
unopposed estrogen effect.
• Estrogen producing tumours (e.g. granulosa cell tumour).
• Irregular Menstrul Periods-Skip menstrual periods or have no
periods at all –continuous unopposed estrogen activity.
• Perimenopause period
• Overweight
• Diabetes Mellitus

6. Types
• Simple hyperplasia - Increased number of glands but regular
glandular architecture
• Complex hyperplasia - Crowded irregular glands
• Simple hyperplasia with atypia - Simple hyperplasia with
presence of cytologic atypia (prominent nucleoli and nuclear
pleomorphism)
• Complex hyperplasia with atypia - Complex hyperplasia with
cytologic atypia

7. Simple Endometrial Hyperlasia
Simple or Cystic Hyperplasia
Proliferation of glands and stroma.
Glands vary in size, some are cystic.
The epithelial cells are active with stratification and mitoses

8. Complex Endometrial Hyperlasia
a very complex gland pattern
abnormally shaped glands, in- and out-pouching.
Glands are crowded with very little endometrial stroma,

9. Atypical Endometrial Hyperplasia
Increased gland density
Nuclear atypia - hyperchromatic, enlarged epithelial cells with an increased
nuclear to cytoplasmic ratio.
Resembles well differentiated carcinoma.

10. Atypical Endometrial Hyperplasia
On high power view the nuclear atypia can be seen:
Nuclei are of variable size, shape and chromatin distribution; prominent nucleoli.

11. Symptoms of Endometrial
Hyperplasia
• Vaginal discharge
• Abdominal pain
• Bleeding between menstrual periods
• Heavy or prolonged menstrual periods

12. Progression of Endometrial Hyperplasia
Type of
Hyperplasia
Total Cases
(n=170)
Years of
Follow up
(mean=13.4)
#
Progressed
to Cancer
%
Progressed
to Cancer
%
Persistent
Hyperplasia
% Spont.
Regression
Simple
93 15.2 1 1% 19% 80%
Complex
29 13.5 1 3% 17% 80%
Atypical,
simple
13 11.4 1 8% 23% 69%
Atypical,
complex
35 11.4 10 29% 14% 57%
Hyperplasia with nuclear atypia has 20-25 % progression to carcinoma
Hyperplasia without atypia has 3% progression to carcinoma

13. Investigations
•Vaginal ultrasound
•Endometrial biopsy
•Dilation and curettage (D&C)
•Hysteroscopy

14. Vaginal ultrasound

15. Focal Simple Hyperplasia

16. Atypical Hyperplasia

17. Endometrial Adenocarcinoma,
Morphology
• May closely resemble normal endometrium
• May be exophytic
• May be Infiltrative
• May be polypoid

18. Endometrial Carcinoma ,
Grading and staging
• Grading is from 1 to 3
• Staging is from 1 to 4
• Stage 1 : Confined to uterus corpus
• Stage 2 : Cervix involvement
• Stage 3 : beyond the uterus ,but within the true pelvis
• Stage 4 : Distant metastasis

19. Endometrial Adenocarcinoma
Clinical Outcome
• First signs are marked leucorrhea and irregular
bleeding ,in a postmenopausal woman
• This reflect erosion and ulceration of the
endometrial surface
• In end stages the uterus might be palpated ,and
in time it becomes fixed to surrounding
structures

20. Endometrial Adenocarcinoma
Survival ,5 year
• Stage 1: 95%
• Stage 2 : 30-50 %
• Stage 3 and 4 : less than 20%

21. Treatment
• In most cases, endometrial hyperplasia can be treated with
medication that is a form of the hormone progesterone.
• Taking progesterone will cause the lining to shed and prevent
it from building up again. It often will cause vaginal bleeding.

22. Treatment for endometrial
hyperplasia without Atypia
• In hyperplasia without atypia, cyclical progestin therapy is the
recommended choice in women not seeking contraception.
• 10 mg MPA for 10 to 14 days a month for 3 to 6 months.
• If they have a normal biopsy and are asymptomatic,
discontinue therapy.
If the hyperplasia is persistent, then continuous-dose
progestin therapy is instituted with 20 mg/day for 3 to 6
months
• In women desiring contraception, OCP can be used or an
injectable depot preparation of MPA can be administered in
the normal dose used for contraception - 150 mg every 12
weeks.

23. Commonly Used Progesterone- Only
Agents
Generic Name Common Trade Names Common Dosage
• Progesterone Crinone;Progestasert;
Prometrium 200 mg PO
• Medroxyprogesterone Provera 10-20 mg PO
Acetate Depo-Provera 150 mg IM
• Megestrol acetate Megace 40-320 mg
PO
• Levonorgestrel Mirena IUS 1 intrauterine every 5
years
More than 98% of women with hyperplasia treated with cyclic progestins experienced
regression of the disease in 3-6 months.

24. Treatment for Atypical endometrial
hyperplasia
• Ideal management is hysterectomy
• If hysterectomy is not a viable option for young
patient & patient is a very poor surgical
candidate),
• high-dose continuous progestin therapy can be
used. Typically, 20 mg of medroxyprogesterone
acetate daily.
• Another option is 40 to 160 mg megestrol
acetate daily for 6 months.
• biopsies every 6 months because of the high risk
of recurrence.

25. Protecting Against
Endometrial Hyperplasia
• Take estrogen with progesterone after menopause
• Women who don't have regular periods-Take oral
contraceptives contain estrogen along with a form of
progesterone.
• If you are overweight, losing weight may help