A lecture on endometrial hyperplasia and carcinoma, exploring the etiology, clinical features, types, investigations, management and treatment options and prognosis.
This was presented to undergraduate medical students at Livingstone Central Teaching Hospital, Livingstone, Zambia, department of Obstetrics and Gynecology by Nghitukuhamba T.E Kalipi (final year student) Cavendish University Zambia, School of Medicine.
4. 2. Endometrial hyperplasia
Endometrial hyperplasia is a condition in which the endometrium becomes
abnormally thick.
It is an estrogen dependent condition, and long-term unopposed estrogen,
particularly around the time of menopause often leads to various types of
endometrial hyperplasia.
Etiology
It develops in women of 40-50 years.
Unopposed estrogen appears to be the primary factor, among other numerous
factors.
Estrogen causes endometrial cells to proliferate when it is unopposed by
progesterone.
6. Endometrial hyperplasia continued..
Protective factors
Multiparity.
Normal weight.
Combined oral contraceptive use.
Progesterone therapy.
Menopause <49 years.
Hysterectomy.
Intrauterine device use (Cu-IUD and LNG-IUS).
Smoking.
7. Endometrial hyperplasia continued..
Diagnosis and investigation
FBC, DC, urea and creatinine, electrolytes, RBS, LTFS.
Urinalysis
ECG and X-ray
There is no classic symptom for premalignant lesions, but the constant
feature is abnormal perimenopausal uterine bleeding. Diagnosis is made by
uterine curettage and histology.
Accidental diagnosis is made during investigation of infertility, DUB, PCOS or
excised specimen of the uterus.
TVUSS.
Hysteroscopy.
8. Endometrial hyperplasia continued..
Histological subtypes of endometrial hyperplasia
Simple hyperplasia: Thickened endometrium, dilated glands with
outpouchings and invaginations. The stroma is more dense and cellular.
Complex hyperplasia: Thickened endometrium, crowded irregular glands
with reduced stroma.
Atypical hyperplasia: Endometrial glands have cytologic atypia with enlarged
and hyperchromatic nuclei.
Carcinoma-in-situ: Lesions with severe cytologic and glandular architectural
abnormalities.
9. Endometrial hyperplasia continued..
Management
1. Preventive treatment.
2. Definitive treatment.
1. Preventive treatment
To maintain ideal body weight.
Screening of at risk women with periodic endometrial sampling.
Reduce use of estrogen alone. COCPs reduce the risk.
2. Definitive treatment
Depends on: Age of the patient and the histological subtype.
Cyclic progestogen therapy (for 6-9 months).
Ovulation induction in cases of PCOS.
Hysterectomy with bilateral salpingo-oophorectomy.
10. 3. Endometrial carcinoma
These are tumours that originate from the lining of the uterus
(endometrium).
Incidence
It is the most common gynaecological malignancy in the UK (95/100000
women).
Life-time risk of developing cancer is 1/46.
Mean age of diagnosis is 62 years, although 25% of endometrial cancer occur
before menopause.
The incidence has risen due to high life expectancy and improvement in
diagnostic modalities.
11. Endometrial carcinoma continued..
Etiology and risk factors
Unopposed estrogen stimulation (PCOS, ovarian tumours) and estrogen
therapy.
Age >62 years.
Nulliparity.
Late menopause >52 years.
Obesity.
Diabetes.
Tamoxifen therapy (SERM).
Family history of colorectal, ovarian, urothelial and endometrial cancer
(Lynch II syndrome).
Endometrial hyperplasia (25% progress to cancer).
12. Endometrial carcinoma continued..
Protective factors
Hysterectomy.
Combined oral contraceptives.
Progestin-based contraceptives, including injectables.
Intrauterine devices, including Cu-IUD and LNG-IUS.
Pregnancy.
Smoking.
14. Endometrial carcinoma continued..
Mechanisms of spread
Direct spread (Myometrium, parametrium, cervix etc).
Lymphatic spread (pelvic, para-aortic, and rarely inguinal and femoral nodes).
Hematogenous spread (involving the lungs, liver, bones and brain).
Clinical features
Symptoms: Postmenopausal bleeding (75%), abnormal uterine bleeding in
premenopausal women, abdominal pain, urinary dysfunction, bowel and
respiratory symptoms, watery and offensive PV discharge (due to pyometra). Less
than 5% remain asymptomatic.
Signs: Varying degree of pallor, bleeding or discharge from cervical os on
speculum examination, and bulky uterus on bimanual pelvic examination. In
some women, pelvic examination is completely normal.
15. Endometrial carcinoma continued..
Diagnosis and investigation
FBC, DC, urea and creatinine, electrolytes, RBS, LTFS.
Urinalysis
ECG and X-ray
Mainstays of diagnosis:
Endometrial biopsy.
TVUSS.
Hysteroscopy.
Other modalities used
MRI
CT
PET scan
16. Endometrial carcinoma continued..
Staging of endometrial carcinoma (FIGO Staging, 2009).
Stage Description
I
IA
IB
Tumour confined to uterine body
Less than 50% myometrial invasion
More than 50% myometrial invasion
II Tumour invades cervical stroma, but does
not extend beyond the uterus
III
IIIA
IIIB
IIIC
Local or regional spread of tumour
Invades serosa of uterus
Invades vagina and/or parametrium
Metastases to pelvic and/or para-aortic
nodes
IV
IVA
IVB
Tumour invades bladder ± bowel ± distant
metastases
Tumour invades bladder and/or bowel
mucosa
Distant metastases, including
intraabdominal metastases and/or inguinal
lymph nodes
17. Endometrial carcinoma continued..
Management
1. Preventive treatment.
2. Curative treatment.
1. Preventive treatment
Maintain ideal body weight.
Restrict the use of estrogen after menopause in non-hysterectomized women.
Patient education on the significance of irregular PV bleeding in
perimenopausal and postmenopausal period.
Screening of high risk women.
18. Endometrial carcinoma continued..
2. Curative treatment
Surgery: Mainstay of treatment for endometrial carcinoma.
Stage I:
Total abdominal hysterectomy (extrafascial) with bilateral salpingo-
oophorectomy.
Vaginal hysterectomy (in patients with uterovaginal prolapse or extreme
obesity).
Laparoscopic hysterectomy with bilateral salpingo-oophorectomy and lymph
node sampling (common iliac, external iliac, internal iliac, obturator and
para-aortic).
Stage II:
Radical hysterectomy with bilateral salpingo-oophorectomy with pelvic and
para-aortic lymphadenectomy.
Combined radiation and surgery.
19. Endometrial carcinoma continued..
Radiotherapy: Used in women who are unfit for surgery, with significant medical
comorbidities, surgically inoperable disease.
The type of radiotherapy used depends on the staging on the disease.
Combination therapy (Radiotherapy and surgery) has a high degree of success.
Radiotherapy 4-6 weeks postoperatively reduces local recurrence, but does
not improve survival.
Brachytherapy for local disease (vaginal vault radiotherapy).
Brachytherapy combined with external beam radiotherapy for locally
advanced disease (stage III).
Chemotherapy: Used in advanced and recurrent cases or in metastatic lesions.
Combination chemotherapy is commonly used.
Drugs include Adriamycin, cisplatin, carboplatin, paclitaxel and
cyclophosphamide.
20. Endometrial carcinoma continued..
Hormone treatment: Used in women not fit for surgery, or those who prefer to
spare fertility.
Progestogens such as 17-hydroxyprogesterone caproate (1g/week, IM),
medroxyprogesterone acetate (1g/week, IM or 150 mg/day PO) or megesterol
acetate (160 mg/day PO). Taken for 3 consecutive months, if responsive,
therapy is continued for longer duration with reduced doses.
Follow-up of patients
Every 4 months for the first 2 years, then every 6 months for the next 2 years
and thereafter, yearly follow-up.
Follow-up includes evaluation of symptoms, clinical examination and chest X-
ray (annually).
21. Endometrial carcinoma continued..
Prognosis
Overall 5 year survival is 80%.
Poor prognostic features include advanced age, grade 3 tumours, type 2
histology, deep myometrial invasion, lymphoreticular space invasion, nodal
involvement and distant metastases.
Stage 5-year survival (%)
I 88
II 75
III 55
IV 16
22. References
Kenny, L.C., Myers, J.E. (2016). Gynaecology by Ten Teachers. 20th Ed, CRC Press,
NW.
Dutta, D.C. (2020). DC Dutta’s Textbook of GYNECOLOGY. 8th Ed, The Health
Sciences Publisher, New Delhi.
