Endometrial pathologies

1. Endometrial
Pathologies
Dr. Indunil Piyadigama

3. Normal
Endometrium
• During the normal menstrual cycle, the endometrium is
proliferative in the follicular phase and is secretory in the
luteal phase.
• Normal proliferative endometrium exhibits no crowding of
glands within the stroma (gland-to-stroma ratio <2:1).
• Normal secretory endometrium may have a gland-to-
stroma ratio of >2:1 .
• Although glands in the secretory phase exhibit crowding,
they are organized, and cells comprising the glands are
spaced and not mitotically active.

4. Endometrial
hyperplasia
• Characterized by irregular proliferation of the
endometrial glands with an increased gland to
stromal ratio
• When Gland to stromal ratio is >2:1
• Lesions that mimic endometrial hyperplasia
include
• Disordered proliferation
• Secretory endometrium
• Benign polyps

5. Epidemiology
• Rare in less than 30 years
• Peak at 50-54 years (common within 1st five years of menopause)
• Precursor of type 1 endometrial cancer
• 3 times as common as the endometrial cancer

6. Risk factors
• Increased endogenous oestrogen
• Anovulation
• Obesity
• Diabetes
• PCOS
• Granulosa cell tumours
• Exogenous oestrogen
• HRT - Cyclical use – Endometrial hyperplasia in 0.7%
• Tamoxifen
• Risk of hyperplasia 2-3 times higher than general population
• Currently restricted for 5 years use only
• Pretreatment screening, prophylactic hysterectomy or endometrial sampling at a low threshold are suggested
interventions

7. • Immunosuppression
• Infection

8. Clinical presentation
AUB – 15% are diagnosed endometrial hyperplasia
Intermenstrual bleeding
Post-menopausal bleeding
Small number can be asymptomatic

9. Diagnosis
TVS Pipelle biopsy D&C
Hysteroscopy and
biopsy
MRI
Immunohistochemical
markers
• PTEN, BCL-2

10. TVS
• ET <7mm unlikely to have endometrial hyperplasia
• Postmenopausal without HRT cut off is set at 4mm
• Postmenopausal with HRT Cut off is taken at 7mm

11. Pipelle biopsy
• Despite negative biopsy 2% of women still can have endometrial
hyperplasia

12. D & C
• Up to 10% of endometrial pathologies missed

13. Hysteroscopy and biopsy
• Better at detecting rather than excluding endometrial pathology. Has
a higher accuracy for CA. 98% sensitive for hyperplasia.

14. Schematic representation of progression of endometrial cancer
Normal endometrial
glands
• Hyperoestrogenism
Simple/ complex
hyperplasia
• MIN
• Mutation K-ras
• Mutation PTEN
Endometrioid
adenocarcinoma G1-
2
• Loss of p16
• HER-2/neu
amplification
• Mutation p53
Endometrioid
adenocarcinoma G3

15. Classification
• WHO 1994
• Simple hyperplasia without atypia
• Simple hyperplasia with atypia
• Complex hyperplasia without atypia
• Complex hyperplasia with atypia
• Carcinoma
• Endometrial intraepithelial neoplasia (EIN) system
• Hyperplasia
• EIN
• Carcinoma
• European
• Hyperplasia
• Endometrial neoplasia
• WHO (modified)
• Hyperplasia without atypia
• Hyperplasia with atypia
• Borderline
• Carcinoma

16. Atypical hyperplasia
• The gland-to-stroma ratio is increased further
• There is a disorganization of glands with luminal outpouching, cellular
mitoses, and nuclear atypia.
• The chromatin may be either evenly dispersed or clumped, and/or
prominent nucleoli may be present

17. Risk of cancer
• Without atypia
• 5% risk of carcinoma over 20 years
• Majority (80%) regress without treatment
• Atypical hyperplasia
• Concurrent carcinomas can occur – 43%
• Progression to CA is 30% in 20 years

18. Endometrial
Cancer
• World-wide second only to cervical cancer from
gynaecological cancers
• Commonest in UK – 50% of new gynaecological cancer cases
• Incidence 17/100 000 women years
• Incidence has been increasing over time
• < 40 years only 5%
• Increases between 40 and 55 years. 20% of endometrial
cancer are seen in premenopausal age
• Thereafter reach a plateau
• Mostly in 60-79 years
• Overall, 5-year survival 80%

19. Endometrial Cancer types
Type 1 Type 2
Incidence 80%
Age 50-60
Perimenopausal
60-70
Postmenopausal
Aetiology Unopposed oestrogen None
Histology Adenocarcinoma - endometrioid
(Arise from glandular epithelium on a background
of atypical hyperplasia)
Adeno - Serous, clear cell
Squamous
undifferentiated, carcinosarcomas
endometrial stromal sarcomas
Grade and spread Minimally invasive
Divided from grade 1-3
Aggressive. Transperitoneal spread is seen.
Other features Stain positive for Oestrogen and progesterone
receptors frequently
Mutations in PTEN tumour suppressor, K-ras
oncogene, mismatch repair genes
P 53 mutation

20. Pathology
• 95% of all endometrial cancers are
adenocarcinomas
• Graded according to cell differentiation
• G1 – Solid areas (non-squamous or non-morular)
5%
• G2 – Solid areas 6-50%
• G3 – Solid areas > 50%
• Nuclear atypia inappropriate for the
architectural grade raises it to the next
tumour grade.
• Nuclear grading takes precedence is serous
and clear cell adenocarcinomas.

21. Histopathology
should include
Histological subtype
Grade
Depth of myometrial invasion
Lymphovascular space invasion
Lymph node involvement
Status of peritoneal washings
Adjacent non-neoplastic endometrium

22. Subtypes of
endometrial
cancer –
WHO
classification

23. Presentation
• 90% will present with postmenopausal bleeding
• 10% of women with postmenopausal bleeding will have
endometrial cancer
• Menstruation continuing after 55 years
• Persistent post-menopausal vaginal discharge due to
pyometra
• Premenopausal worsening of menstrual pattern
• Abnormal endometrial cells in cervical cytology (50% of
cancers can have cells in cytology)

24. Endometrial hyperplasia?
a. Endometrial sampling is highly specific and sensitive
b. Hysteroscopy with D &C may yield higher detection rate of focal
pathology
c. Hyperplasia calssification done based on cytological
characteristics of the lesions
d. Endometrial cancer is the most common gyn cancer in
developed world.

25. Endometrial hyperplasia?
a. Associate with relatively deficiency of progesterone
b. PCOS is a risk factor
c. Lynch syndrome greatly increased the risk of hyperplasia
d. Abnormal uterine bleeding is not an initial symptom among
many.

26. • A 48-year-old woman presents with a four-month history of heavy menstrual bleeding and
prolonged menstrual cycles (45-50 days). Her past medical history is significant for uncontrolled
hypertension and bronchial asthma, and her obstetric history includes three cesarean section
deliveries. She reports a history of multiple sexual partners, and her BMI is 35 kg/m2.
Examination is notable for excess facial and body hair. Transvaginal sonography shows an
endometrial thickness of 25 mm. Given the likely diagnosis, which patient factor most increases
her risk for this condition?
• A. Uncontrolled hypertension
• B. Multiparity
• C. History of multiple cesarean sections
• D. BMI of 35 kg/m2

27. • A 35-year-old overweight woman presents with chief complaints were
polymenorrhea and abnormal uterine bleeding. A direct biopsy of the
endometrium was done, and the specimen was sent to a pathological lab
for further examination, which revealed well-differentiated normal-shaped
cells. What is the most likely diagnosis?
• A. Endometrial adenocarcinoma
• B. Endometrial hyperplasia without atypia
• C. Asherman syndrome
• D. Endometriosis

28. Thank you
Special thanks to Dr. Sathya Sendanayaka