Endometrial cancer is the most common gynecologic malignancy in the U.S. and has rising incidence rates, with key risk factors including obesity and unopposed estrogen therapy. The document outlines classification, clinical features, diagnosis, treatment options, and pathogenesis of endometrial hyperplasia and cancer, emphasizing the importance of histologic evaluation and tailored treatment plans. Preventive measures such as routine screening for high-risk women and education are also highlighted.

1. Endometrial Cancer
Girma Hirpasa ( MD, Assistant professor Obstetrics and Gynecology)

2. Outline
• Epidemiology and risk factors
• Endometrial hyperplasia
• Classification
• Clinical features and diagnosis
• Treatment
• Endometrial cancer
• Pathogenesis
• Prevention
• Diagnosis
• Pathology
• Treatment

3. Epidemiology
• In the US, endometrial cancer is the most common gynecologic
malignancy
• fourth most common cancer, ranking behind breast, lung, and bowel
cancers
• sixth leading cause of death from malignancy in women
• incidence of endometrial cancer continues to rise

4. Risk Factors for Endometrial Cancer
Characteristic Relative Risk
• Nulliparity 2-3
 Early age of menarche
• Late menopause 2.4
• Obesity*
– 21-50 lb overweight 3
– >50 lb overweight 10
• Diabetes mellitus, HTN 2.8
• Unopposed estrogen therapy* 4-8
• Tamoxifen therapy 2-3
• Atypical endometrial hyperplasia* 8-29
• HNPCC syndrome* 20

5. What are the risks for Long-term estrogen
exposure and Chronic Anovulation?
Polycystic ovary syndrome
Functioning ovarian tumors
Menopausal estrogen therapy without progestin
Insulin Resistance

6. Protective factors
• OCP
• PM Combined HRT
• Smoking
• Exercise
• High Parity

7. Endometrial Hyperplasia
• endometrial hyperplasia is the only known direct precursor of
invasive disease.
• It is defined as endometrial thickening with the proliferation of
irregularly sized and shaped glands and an increased gland-to-stroma
ratio
• In the absence of such thickening, lesions are best designated as
disorderly proliferative endometrium or focal glandular crowding

8. Classification of Endometrial Hyperplasia
WHO Classification of Endometrial Hyperplasia(2014)
Types Progressing to Types
Cancer (%)
Simple hyperplasia 1
Complex hyperplasia 3
Simple atypical hyperplasia 8
Complex atypical hyperplasia 29

9. Classification of Endometrial Hyperplasia…
Endometrial intraepithelial neoplasia (EIN) is a term introduced to
more accurately distinguish the two very different clinical categories of
hyperplasia (recognized by the ACOG and SOG,2017a)
• These are:
(1) normal polyclonal endometrial diffusely responding to an abnormal
hormonal environment(without atypia) and
(2) intrinsically proliferative monoclonal lesions that arise focally and confer an
elevated risk of adenocarcinoma(with atypia)

10. Clinical Features
• Postmenopausal bleeding(2/3rd of AUB)
• Premenopausal women with AUB
• PMP- women with a pyometra

11. Diagnosis
• histologic diagnosis
• Pipelle office endometrial biopsy (EMB) or outpatient D & C
• hysteroscopy is more sensitive to focal endometrial lesions
• The ACOG(2016) recommends an Endometrial sample for women;
older than 45 years with AUB.
younger than 45 with chronic excess estrogen exposure, failed medical
management, and persistent AUB.
 postmenopausal bleeding with endometrial thickness >4mm(TVS)

12. Transvaginal sonography
‘predict endometrial hyperplasia’

13. Treatment
 mainly depends on
• patient's age,
• comorbid risks for surgery,
• desire for fertility, and
• specific histologic features such as cytologic atypia.
• Hysterectomy is the most definitive treatment
• Hormonal therapy is another option

14. Treatment…
1.Nonatypical Endometrial Hyperplasia
• Premenopausal Women-may spontaneous regress without therapy
-progestins
• Postmenopausal Women-progestin
• The overall clinical and pathologic regression rates to progestin
therapy range from 70 to 80%

15. Treatment…
2.Atypical Endometrial Hyperplasia
• Hysterectomy is the preferred treatment
-progression to cancer over time approximates 29%

16. ENDOMETRIAL CANCER
Pathogenesis
characterized by a dualistic model
1.Type I endometrioid adenocarcinomas
• estrogen-dependent, low grade, and derived from atypical endometrial
hyperplasia
2.Type II cancers are serous, carcinosarcoma, or clear cell histology
• have no precursor lesion; and portend a more aggressive clinical course

17. ENDOMETRIAL CANCER…cont’d
Type I and II Endometrial Carcinoma Distinguishing Features
Feature Type I Type II
oChronic estrogen present absent
oMenopause status pre-/peri post-
oHyperplasia present absent
oRace white black
oGrade low high
oInvasion Minimal deep
oBehavior stable aggressive
oSubtypes endometroid serous, clear cell

18. Prevention
• Education
• Counseling
• routine screening of hyperplasia or endometrial cancer??
• Recommended screening(EMB) is for the woman with Lynch
syndrome
every 1 to 2 years beginning at age 30 to 35 years(ACOG,2019)

19. Diagnosis
Signs and Symptoms
• Irregular vaginal bleeding-In premenopausal women
• Postmenopausal bleeding
• Abnormal vaginal discharge-in older women
• pelvic pain or pressure, bloating, early satiety, and increasing
abdominal girth—advanced disease

20. • Papanicolaou Test-benign endometrial cells(>45years)
-atypical glandular cells
• Endometrial Sampling-Office Pipelle biopsy or D and C
-MVA*
-hysteroscopy

21. • Laboratory Testing
• serum CA125 level-monitoring
• Imaging Studies-Before diagnosis-TVS
-After diagnosis CT-scan/MRI-High grade lesions

22. Pathology
The spectrum of aggressiveness within the histopathologic types of
endometrial cancer is broad
Classification of Endometrial Carcinoma
Endometrioid adenocarcinoma-80%
o Variant with squamous differentiation
o Villoglandular variant
o Secretory variant
o Ciliated cell variant
Mucinous carcinoma-1-2%
Serous carcinoma—5-10%
Clear cell carcinoma
 Mixed cell carcinoma—10%
 Neuroendocrine tumor
 Undifferentiated carcinoma
 Squamous cell carcinoma
 Carcinosarcoma
 Others

23. Histologic grade
-Histologic grading is primarily determined by the tumor's
architectural growth pattern
Grade Definition
1 5% of a nonsquamous or nonmorular solid growth pattern
2 6-50% of a nonsquamous or nonmorular solid growth pattern
3 >50% of a nonsquamous or nonmorular solid growth pattern

24. Patterns of Spread
• Type I endometrioid tumors and their variants most commonly
spread in order of frequency, by:
• (I) direct extension, (2) lymphatic metastasis,(3) Hematogenous
dissemination, (4) intraperitoneal exfoliation.
• Type II serous and clear cell carcinoma and carcinosarcoma have a
particular propensity for extrauterine disease, in a pattern that closely
resembles epithelial ovarian cancer

25. Patterns of Spread…
• Invasion of endometrial stroma and exophytic expansion
• Lymphatic channel invasion haphazard pattern
• Hematogenous dissemination-- most commonly results in metastases
to the lung to the liver, brain, bone, and other sites
• Retrograde transtubal transport
• Port-site metastasis-laparoscopic staging

26. Treatment
• Surgical treatment
• Chemotraphy
• Radiotherapy

27. FIGO STAGING,2019

28. References
• Williams Gynecology 4th edition, 2020.
• Berek & Novak’s Gynecology 16th edition,2020.
• Current obstetrics and gynecology diagnosis and treatment, 11th
edition.

29. Thank you