Endometrial cancer By:- Dr Kiran Pandey/ Dr Pavika Lal

1. ENDOMERIAL CANCER: DETECT IT EARLY
SPEAKER
Dr Kiran Pandey
Professor and Head
Department of Obstetrics and Gynaecology
GSVM MEDICAL COLLEGE KANPUR
ICOG Governing Council Member(2020-2021)
Secretary UPSC AGOI(2017-2019)
President KOGS(2016-2018)

2. EPIDEMIOLOGY
 4th most common cancer in women worldwide and 8th leading
cause of death from malignancy in women.
 Most common gynaecological malignancy worldwide
 More prevalent in high income countries(5%) with increasing
prevalence in Low income Countries(4%) with increased
specific mortality in latter.
 25% of endometrial carcinomas are diagnosed in pre
menopausal women and 5% in women upto 40yrs (specially
with significant risk factors)
 Endometrial atrophy is the most common cause of PMB (60-
80%) and only 10% of pts with PMB harbour Ca
Endometrium.
 2-3% lifetime risk with 5 year survival rate of 81% if detected
early
 90% patients have abnormal uterine bleeding as the only
presenting symptom and <5% are asymptomatic.
Why Ca Endometrium spares?
Due to early presentation and diagnosis attributing to
high rate of survival

3. TYPES OF CA ENDOMETRIUM
 Associated with
Hyperestrogenism
 Associated with
Hyperplasia
 Patients usually Peri-
Menopausal
 Usually Endometrioid
and mucinious Subtypes
 Favourable Prognosis
 Not related to
hyperestrogenism
 Usually arises in
background of atrophic
Endometrium
 Postmenopausal Patients
 Usually serous or clear
cell subtypes
 Aggressive, Poor
Prognosis
TYPE 1 TYPE 2

4. PREDISPOSING FACTORS
 Age (50-70 years) risk- 1-4%
 Early menarche (<12yrs)
 Late menopause after 55 years relative risk is 2
 Nulliparity- relative risk 2
 Unopposed and unsupervised HRT- RR 2-10
 Chronic anovulatory cycles
 Strong familial predisposition such as-:
Positive family history of breast, ovarian, and to lesser
extent colon cancer.(HNPCC syndrome)- 21-77%
during lifetime
Cowden syndrome (PTEN mutation): 13- 19% during
lifetime

5. • Use of Tamoxifen: RR 2
• Obesity, Diabetes, Hypothyroidism, Hypertension
(corpus cancer syndrome)
• Infertility, Polycystic ovarian syndrome (RR 3)
• Estrogen producing ovarian tumours like sertoli cell
tumors
Most important risk factor is long term exposure to
endogenous or exogenous estrogen unopposed by
progesterone
Protective Factors are-:
• Physical Activity
• OCP use for more than 5yrs confers a protection of
50% against Ca Endometrium.

6. PREVENTIVE STRATEGY FOR ENDOMETRIAL
CANCER IN NEAR FUTURE?
 A pragmatic risk prediction model to stratify
female population into low, medium and high
risk category depending on 4 variables
 Genetic risk score
 Reproductive risk score
 Insulin risk score
 Obesity risk score.
 The flow chart concerned with the risk
prediction model is depicted as follows.

7. RISK SCORE
G+I+R+0
LOW RISK
(-6 TO 2)
MEDIUM
RISK
(3 TO 7)
HIGH
RISK
(>8)
DIET AND
EXERCISE
DIET AND
EXERCISE
DIET AND
EXERCISE
REASSESS
IN 5YRS
MIRENA OR
METFORMIN
+ASPIRIN
MIRENA and
METFORMIN+ASPIRIN
+/-
BARIATRIC SURGERY
Reference Sarah J Kitson etal Identifying High Risk Women Endometrial
Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk
Prediction Model. Cancer Prevention Research;December 2016

8.  Endometrial hyperplasia represents exaggerated
proliferation of endometrium characterized by excessive
growth of glands/ stromal ratio with or without
cytological atypia
Simple hyperplasia without
atypia
1%
Complex hyperplasia without
atypia
3%
Simple hyperplasia with atypia 8%
Complex hyperplasia with atypia 28%
30-40% of endometrial cancers are found in a background of
atypical hyperplasia. Overall these tend to be low grade tumors
ENDOMETRIAL HYPERPLASIA

9.  Evaluation of women suspected of endometrial cancer
involves detailed history taking:
 Menstrual cycle with respect to frequency, regularity,
duration, volume, age of menarche and menopause
occured
 History of previous cervical cytology
 Detailed personal history with respect to medical
disorders
 History of medication like HRT, tamoxifen
 Detailed family history with respect to age of cancer
diagnosis as well as family degree of relationship for
breast, endometrial, ovarian and colorectal cancer
A comprehensive and systematic history taking is
important for identification of risk factors of endometrial
cancer and further the chance of harbouring the
endometrial cancer in patient presenting with AUB in
premenopausal age group and PMB in postmenopausal
age group.

10. ENDOMETRIAL INTRAEPITHELIAL
CARCINOMA(EIN)
 Endometrial Intraepithelial Neoplasia(EIN) is recently coined
by International Endometrial Collaborative Group.
 EIN is a clonal proliferation of architecturally and
cytologically altered premalignant endometrial glands, which
are prone to malignant transformation to endometrioid (type
I) endometrial adenocarcinoma
 Histomorphologic, genetic, clinical, and biological data were
used to develop quantitative pathologic criteria for three
disease categories:
 Benign endometrial hyperplasia,
 Endometrial intraepithelial neoplasia (EIN; premalignant),
 endometrial adenocarcinoma endometrioid type, well
differentiated

11. DIAGNOSTIC CRITERIA FOR ENDOMETRIAL
INTRAEPITHELIAL NEOPLASIA
Nomenclature Topography Functional
Category
Treatment
Benign
endometrial
hyperplasia
Diffuse Prolonged
estrogen effect
Hormonal
therapy,
symptomatic
Endometrial
intraepithelial
neoplasia
Focal progressing
to diffuse Precancerous
Hormonal therapy
or surgery
Endometrial
adenocarcinoma,
endometrioid
type, well-
differentiated
Focal progressing
to diffuse
Malignant
Surgery, stage-
based

12. POPULATION TO BE INVESTIGATED IN ORDER
TO DIAGNOSE ENDOMETRIAL CANCER EARLY
 Post menopausal women with history of post menopausal
bleeding regardless of volume, duration and frequency.
 Post menopausal women with ET on TVS > 4mm
regardless of presence or absence of PMB
 Women >45 years of age presenting with AUB
 Women of <45 years of age with failure of medication
therapy for AUB.
 premenopausal women presenting with anovulatory
amenorrhoea of >6months with ET>7mm
 Women with cervical cytology presenting atypical
glandular cells of all sub categories.
 Women with Lynch II syndrome or Cowden syndrome
needs screening.

13. EXAMINATION
 A detailed gynaecological examination to rule out
local lesions of vulva, vagina and cervix is
important
 A bimanual examination is done to know position ,
mobility, size of the uterus as well as presence or
absence of any adnexal masses
 General examination of breast and thyroid
 Lymphadenopathy(supraclavicular , inguinal)
should always be ruled out

14. CHARACTERISTIC FEATURES OF
ENDOMETRIAL CARCINOMA
 Approximately 80% of Endometrial Cancers have
following characteristics:-
• Endometroid adenocarcinoma
• Well Defined
• Lesion confined to uterus at time of diagnosis
o Most Important Prognostic factor:-
• FIGO staging
• Grade
• Depth of Myometrial Invasion

15. INVESTIGATIONS
According to recent ESGO/ ESMO: Following are the
methods to detect endometrial cancer early:
 Pelvic examination
 Trans-Vaginal Sonography(TVUS)
 Histological assessment (Type and Grade)of
Endometrial Aspirate/Biopsy
ESGO-European Society of Gynaecologic Oncology
ESMO-European Society of Medical Oncology
Following investigations are only advisable in cases where
diagnosis is inconclusive.
 Saline Infusion Sonography(SIS)
 Hysteroscopy guided biopsy

16. TRANS-VAGINAL ULTRASONOGRAPHY(TVUS)
 TVUS is a safe, non invasive,reliable and cost-effective way
to evaluate the endometrium, both to visualize focal lesions
and assess endometrial thickness(ET).
 Technique involves scanning the uterus in a sagittal view
and measuring the double-layer ET in the anteroposterior
dimension from one basalis layer to the other.
 Endometrial Biopsy is a substandard test for diagnosing
benign endometrial abnormalities (such as polyps and
submucosa leiomyomas), TVUS may be a better starting
point for women at lower risk for endometrial cancer.

17.  TVUS should be performed before attempting an EB as
this may affect the appearance of endometrium
 If EB already taken, an USG should be delayed by 2
weeks.
 Other Pathologies detected upon TVUS are-:
 Suspected Uterine Polyp
 Uterine Fibroid
 Ovarian Malignancy
FIBROIDENDOMETRIAL
POLYP

18.  (ACOG-2018) concluded that when the endometrium
measures ≤4 mm with TVUS, the likelihood that bleeding is
secondary to endometrial carcinoma is less than 1%(negative
predictive value 99%)
 A thickened endometrium on TVUS (>4 mm in a
postmenopausal woman with PMB) warrants additional
evaluation with endometrial sampling.
Endometrial biopsy is
not recommended

19. Sonographic features are non specific and endometrial
thickening can also be due to benign proliferation due to
endometrial hyperplasia or polyps.
Ultrasound features that are suggestive of endometrial
carcinoma rather than hyperplasia include:
• Heterogenous and irregular endometrial thickening
• Polypoid mass lesion
• Intrauterine fluid collection
• Frank myometrial invasion
In additional TVS helps in subjective evaluation of
myometrial as well as cervical stromal invasion
A thin endometrial echo doesn’t exclude
reliably Type 2 Endometrial Cancer
therefore repeated and ongoing episodes of
PMB always require histologic evaluation.

20. TVUS
evaluation of
PMB, with
endometrial
thickness 4.7
cm.

21. Transvaginal ultrasound for preoperative assessment of
myometrial invasion in patients with endometrial cancer
There are two approaches of assesment of myometrial invasion
1. Gordon ratio- distance between endometrium–
myometrium interface and maximum tumor depth to the
total myometrial thickness) with cutoff of 0.5

22. 2. Karlsson Ratio (endometrial
tumor
thickness/anteroposterior
uterine diameter ratio), in
women with endometrial
cancer with cut off >0.5
From the above 2 ratios, the sensitivity and specificity to
detect myometrial invasion varies from 63-93% and 72-
92% respectively
Mascilini F., Testa A. C., Van Holsbeke C.. Evaluating
myometrial and cervical invasion in women with
endometrial cancer: comparing subjective assessment
with objective measurement techniques. Ultrasound in
Obstetrics and Gynecology. 2013

23.  After aggressive research and meta-analysis the following conclusions
were reached-:
 TVS screening in asymptomatic patients for the early detection of
endometrial carcinoma is not cost-efficient.
 Moreover it leads to unnecessary interventions for harmless findings.
 However, even though the validity of TVS for screening has
currently not been proven, the method should still be an integral part
of gynaecological examinations.
Alcázar J. L., Orozco R., Martinez-Astorquiza Corral T., etal. Transvaginal
ultrasound for preoperative assessment of myometrial invasion in patients
with endometrial cancer: a systematic review and meta-analysis. Ultrasound
in Obstetrics and Gynecology. 2015;46(4):405–413.

24. Role of colour doppler in evaluation of
postmenopausal endometrium
Color Doppler helps to detect increased vascularity and
therefore helpful in assessment of following cases:-
Thin endometrium with intrauterine fluid collection in
postmenopausal females
To differentiate between cancerous and hyperplastic
thickened endometrium
 ET b/w 5 to 10mm with no h/o PMB and Endometrial
biopsy is inconclusive – Color Doppler may help to avoid
unnecessary biopsies.
When ET > 10mm – 90% chance that patient
has Endometrial cancer
When ET is between 5-10 mm there is only 10%
chance that patient has Endometrial cancer
Color Doppler helps to evaluate in patients
with Endometrial thickness between 5-10mm

25. SALINE INFUSION SONOGRAPHY
 SIS is expensive and uncomfortable, it is used mainly as a
second step in the evaluation of PMB.
 Useful when -:
 Diagnosis remains unclear after endometrial biopsy
 TVUS is suggestive of a focal lesion with persistence of
bleeding to confirm the presence of intracavitary pathology
 Patient has a relative contraindication for hysteroscopy
with EB.
.
SIS is contraindicated in cases in which cancer
cells were detected with either EMB or TVUS, as
the procedure has been associated with a small
but real risk of malignant cell dissemination

26. SALINE
INFUSION
SONOGRAPHY

27. ENDOMETRIAL TISSUE SAMPLING
 Endometrial sampling is important to differentiate between
various types of endometrial hyperplasia so as to confer the
risk stratification for development of endometrial cancer.
 Endometrial tissue can be obtained by
1. Endometrial aspiration/biopsy
2. Fractional Curettage
3. Hysteroscopy guided endometrial biopsy

28. EB should be performed after TVUS when there are
following findings can be gathered in a post
menoapausal female-:
 Endometrial Thickness > 4mm
 Endometrial Thickness > 3mm with fluid in
Endometrial Cavity
 Suspicion of Polyp or Mass regardless of Endometrial
Thickness
 ET not visualized
 Persistent PMB regardless of ET (no need for further
assessment if the Pipelle report has been negative in the
last 6 months)
In patients who are on tamoxifen therapy 8mm cut off
warrants endometrial biopsy
endometrium thicknes of >11 mm has been proposed as a
threshold for endometrial biopsy in premenopausal age group

29.  The Endometrial sampling using Pipelle aspirator has replaced the
conventional fractional curettage as well as D&C because, it is a
1. Safe
2. Accurate
3. Cost effective outpatient procedure
4. Avoids general anesthesia
5. High sensitivity and specificity for detection of endometrial
hyperplasia and endometrial carcinoma
Diagnostic accuracy of Endometrial Biopsy is around
87-100% but with use of Pipelle Aspirator it increases
to around 99% in both Pre and Post Menopausal
females.

30. LIMTATIONS OF FRACTIONAL
CURETTAGE
 Inadequate sampling
 10% of endometrial conditions remain undiagnosed
(polyp, myomas)
 Endometrial hyperplasia and focal endometrial
carcinomas are not diagnosed
 GA and dilatation of cervix is necessary requiring
Hospitalization
 A/w increased risk of complications (uterine perforation,
bleeding, infection)
Therefore Fractional Curettage not currently
recommended

31. A negative tissue biopsy result in women with PMB is not
considered to be an endpoint, and further evaluation
with hysteroscopy to evaluate for focal disease is
imperative especially if the bleeding persists.
CLINICAL
TAKEAWAY

32. HYSTEROSCOPY
Indications include:
 Unable to pass Pipelle sampler
 Suspected polyp
 Inadequate visualization of the endometrium
 Recurrent PMB (defined as 2 visits to OPD with 2 benign
Pipelle biopsy more than 6 months apart in the last 2
years)

33. ROLE OF HYSTEROSCOPY IN ENDOMETRIAL
CAVITY EVALUATION
Hysteroscopy is the gold standard for evaluation of
 Uterine cavity
 Diagnosing intrauterine pathology
 Operative interventions for other causes of AUB
Hysteroscopic view of Type 0
Fibroid

36. MORPHOLOGIC CLASSIFICATION OF
HYSTEROSCOPIC IMAGES
INVOLVEMENT GROSS APPEARANCE ORIGIN
Circumscribed
Diffuse
Polypoid(MOST
COMMON)
Nodular
Papillary
Ulcerated
Primary
Metastatic
ADAPTED FROM Sugimoto Et Al

37. HYSTEROSCOPY: TO DO OR NOT TO DO???
 There is some concern that hysteroscopy results in spillage of malignant
cells into the peritoneal cavity and upstage the disease but to avoid this
 Keep the operating time < 10 mins,
 Distension media should be preferrably CO2 as compared to liquid
media ( dextran 70, normal saline)
 Intrauterine pressure should be <70-100 mmHg
Georglos et al Role of hysteroscopy in endometrial cancer: research
gate article 2015
Hysteroscopy is an additional tool in diagnosis of
endometrial cancer but its initial role is still
controversial
Moreover malignant endometrial cells disseminated into
peritoneal cavity are rarely viable.
Diagnostic hysteroscopy has no adverse effects on prognosis
and 5 yrs survival in stage 1 patients.

38. Will screening for endometrial
cancer soon be routine?
Probably No
Most pts present early with abnormal perimenopausal
or postmenopausal bleeding when tumour is still confined
to the uterus.
Application of appropriate and accurate diagnostic test
results in early diagnosis, timely treatment and high cure
rate.

39.  In a female with average risk with no symptoms , at
present no screening test is advisable
 ACS recommends that all females should be educated
about risk factors and signs and symptoms of
endometrial cancer and strongly encourage to report
abnormal uterine bleeding, discharge or spotting to the
physician
 No screening is recommended in women on continuous
therapy of HRT

40.  Women on sequential therapy of HRT are advised for
annual TVS after completion of progestational phase
(D2) of cycle
 In females with presence of risk factors any amount of
abnormal uterine bleeding should be thoroughly
investigated and endomterial cancer should be ruled out
by histopathological diagnosis.
 In females who are at high risk (HNPCC syndrome)
genetic counselling is warranted and should be offered
yearly testing for endometrial evaluation after the age of
35 yrs.

41. TAKE HOME MESSAGE
 Endometrial Cancer usually carries good prognosis due
to its early presentation
 It is usually a disease of postmenopausal or
perimenopausal women presenting with PMB and AUB
respectively.
 Early diagnosis can be made by identification of risk
factors and Transvaginal USG
 Endometrial aspiration can diagnose almost 99% of
endometrial cancers effectively.
 At present no screening technique is advisable in average
risk women or women with risk factors except in Lynch
II/Cowden Syndrome.
 SIS and Hysteroscopy are useful in inconclusive cases.

42. THANK YOU