ENDOMETRIAL CARCINOMA

1. Dr. Neha Jain
Dept. Obs & Gyn
Jawaharlal Nehru Medical College
& Hospital
A.M.U., Aligarh

2. Learning objectives
The learner will be able to understand:
The nature of endometrial cancer
The various preventable & non preventable risk
factors of endometrial ca.
The pitfalls in screening of this carcinoma
The evaluation & management of a case of
endometrial carcinoma.

3. INTRODUCTION
In U.S. it is the most common malignancy of
the female genital tract.
 4th most common cancer after breast, lung &
colorectal cancer.
 8th most common cause of death from malignancy.
Incidence of endometrial cancer is very low in
India.
 Highest in Delhi – 4.3/ lac
 Bangalore – 4.2/ lac
 Mumbai – 2.8/ lac

4. types
TYPE- I :- Estrogen Dependent (Unopposed estrogen) (75-85%)

Perimenopausal age
 Hyperplastic endometrium  Carcinoma
 Better differentiated
 Favourable prognosis
Type- II :- Estrogen Independent (15-25%)





African American & Asian women
Post menopausal women
Atrophic endometrium Carcinoma
Less differentiated
Poorer diagnosis

9. 21-50 lb over wt.- 3 times
>50 lb over wt.- 10 times
Most common cause of
endogenous production of
estrogen (Williams gyne)
Coexisting medical
condition /
sequele- HTN, DM & Gall
bladder disease increases
risk
(Williams gyne)

11. Corpus cancer syndrome
Corpus
cancer
obesity

13. Risk also increases with :
> Duration of therapy
> Cumulative dose

14. WITHOUT ATYPIA (1%)
WITH ATYPIA (8%)
WITHOUT ATYPIA (3%)
WITH ATYPIA (29%)

17. -II
<5% of endometrial cancer
Hereditary non polyposis colorectal cancer
syndrome (HNPCC).
Autosomal Dominant disorder
Germline mutation in mismatch repair gene,
MLH1, MSH2 & MSH6.
Colorectal, endometrial, ovarian, gastric,
ureter &
skin cancer.
40-60% life time risk of endometrial and
colorectal
cancer.
Cancer tends to occur in premenopausal
age.
Life time risk of ovarian cancer-10-12%.

18. Preventing factors
Oral contraceptive pills1 yr. of use confers 30-50% reduced risk
Risk reduction is upto 10-20 yrs.
Progestin component has chemo protective role
Progesterone IUCDs confers long term protection.
Earlier age of menopause
Smoking
Factors decreasing estrogen.

20. Screening tests

Pap smear
 Progesterone challenge test
 TVS
 Endometrial biopsy
 VABRA or Pipelle

22. Screening=???...
Disease is not so prevalentPap test:
Inadequate
Insensitive
 Screening test should be:
 Acceptable
Progesterone challenge test:
 Reproducible
Inconclusive
 Valid (sensitivity)
Trans vaginal sonography:
 Cost effective
Too expensive
Invasive

Endometrial biopsy:
Too expensive
Invasive

24. The current tests can only detect
half of all cases of Ca.
endometrium

26. EARLY DIAGNOSIS & TREATMENT
 If a lady comes with:
 Premenopausal AUB
 Post menopausal BPV
 Abnormal perimenopausal BPV
 25% of the endometrial cancer occurs premenopausally.
 5% under the age of 40 yrs.
 Early diagnosis & prompt treatment has high cure rate.

27. 10% (HNPCC or predisposition for endometrial
cancer
alone)
Autosomal dominant
What to do in these patients ???
There are 2 alternativesAnnual
pelvic examination, TVS & EB from the
age of 30-35yrs.
OR
Prophylactic TAH & BSO after completion of child
bearing (Preferred Alternative)

28. Classification of
endometrial cancer
(Histological)
Endometroid adenocarcinoma
 With squamous differentiation
 Villoglandular/ papillary
 Secretory
Mucinous carcinoma
Papillary serous carcinoma
Clear cell carcinoma
Squamous carcinoma
Undifferentiated carcinoma
Mixed carcinoma

29. Differentiation is expressed in grades (which in
determined by architectural growth pattern & nuclear
features):
G1- < 5% of the tumor shows solid growth pattern
G2- 6-50% shows solid growth pattern
G3- >50% shows solid growth pattern
If nuclear atypia is present c is inappropriate for the
architectural grade – raises grade by 1 grade.
In endometroid ca. with squamous differentiation,
serous, clear cell and squamous ca. nuclear grading
takes precedence.

30. Endometroid adenocarcinoma



~80% of endometroid
carcinoma
Composed of glands that
resemble normal
endometrial gland
D/d- Atypical hyperplasiaDifferentiated by
presence of invasion.

31. Endometroid adenocarcinoma

32. Variants of endometroid
ca.
Squamous differentiation (15-25%)
Villoglandular/ papillary (2%)
Secretory (1%)

33. Mucinous carcinoma
5% of endometrial
carcinoma
On half of the tumor is
composed is composed
of cells with
intracytoplasmic mucin.
Prognosis is good
D/d- Endocervical
adenocarcinoma

34. Serous carcinoma
3-4% of the endometrial
carcinoma
Elderly
Hypoestrogenic women
Aggressive
Often associated with
Lympho-vascular & deep
myometrial invasion
Prognosis-poor
Accounts for 50% of the
deaths from endometrial cancer

35. Clear cell carcinoma
<5% of the endometrial
carcinoma
Elderly
Mixed histological
pattern
Cells have Hobnail
configuration
Prognosis- very poor
Survival rate- 33-64%

36. Squamous carcinoma
Rare
Often associated with
cervical stenosis,
chronic inflammation
& pyometra.
Prognosis- poor
Survival rate-36% in
stage-I

37. Simultaneous tumors of
endometrium & ovary
Most frequent simultaneously occurring
genital malignancies
Incidence- 1.4-3.8%
Both are well differentiated
Prognosis -Excellent
Mostly postmenopausal
C/f : AUB (ovarian ca diagnosed
incidentally)
29% of endometroid adeno ca. of ovary
have associated endometrial cancer.

38. Clinical features

Average age of presentation- 60 yrs.
Mostly 6th & 7th decades of life.
5% presents premenopausally (Novaks 15
th

ed.)
Presenting symptoms:
Vaginal bleeding
Vaginal discharge (may be purulent)
Pelvic discomfort/ pain (due to uterine enlargement
due to mass or hematometra or pyometra or
extrauterine d/s spread)

< 5% - Asymptomatic

39. Causes of post menopausal BPV ???
Post menopausal
BPV
Genital
Non-genital
Uterine
Extra-uterine
Endo. Atrophy(60-80%)
Estrogen replacement (15-25%)
Endo. Hyperplasia (5-10%)
Endo. polyp (2-12%)
Endometrial Ca (10%)
Ca. cervix, vagina & vulva
Atrophic vaginitis
Traumatic bleeding
Urinary
Gastro intestinal
Hematological

40. Points never to be forgotten
Post menopausal BPV is seen in 3% of the post
menopausal patients.
Amount & type of bleeding is not important
20% of the cases with post menopausal BPV
have significant pathology
The primary aim is to exclude Atypical
Hyperplasia & Endometrial Carcinoma.
It is easier to diagnose than to exclude

41. History &Physical examination
History: Obesity, Diabetes, Hypertension, bladder &
bowel symptoms
Gen. Examination:
Weight
LN enlargement (Inguinal, abdominal)
Breast examination
P/A exam: +ve in advanced disease
Ascites
Hepatic or omental metastasis
Pelvic exam: Vaginal introitus, sub urethral area, vagina,
cervix
P/V exam., P/R exam. (uterus, adenexa,
parametrium, cul-de-sac)

42. investigations
Routine investigations
Transvaginal sonography*
Office based endometrial biopsy (VABRA or
Pipelle)*
Endocervical curettage (in suspected cervical
pathology)
Only used if there is:
Hysteroscopy
Cervical stenosis
Dilatation & Curettage
Recurrence of bleeding
after –ve OBEB
Inadequate sampling in
specimen

44. Pre treatment evaluation
Examination:
Routine investigations:
ECG
Chest X-ray
CA-125- ↑sed in advanced metastatic Ca.
USG & MRI- Degree of invasion
Cystoscopy, Colonoscopy, IVP, Barium
enema- acc. to symptoms

45. Surgical Staging
Hysterectomy
B/L Salpingo-oopherectomy
Biopsy of all metastatic deposits
Peritoneal fluid cytology
Cytology in clockwise fashion
Pelvic & Para-aortic LN dissection only in high
risk-
Tumor size >2cm.
Grade-III tumor
Non endometroid tumor

46. Figo 2009 staging
Stage I- Tumor confined to corpus uteri
IA- No or <50% of myometrial invasion
IB- >50% of myometrial invasion
Stage II- Tumor invades cervical stroma, but does
not extend beyond the uterus
Stage III- Local &/or regional spread of tumor
IIIA- Serosa of uterus &/or adenexa
IIIB- Vaginal &/or parametrial involvement
IIIC- Pelvic (IIIC1) &/ or Para-aortic LN (IIIC2)
Stage IV- Bladder &/or Bowel mucosa &/or distant
mets.
IVA- Bladder &/or Bowel mucosa
IVB- Distant metastasis

47. ROUTES OF METASTASIS
Pattern of spread




Contiguous
extension:
Hematogenous:
Lymphatic:
Peritoneal:
Predictors





Grade 3 & LVSI
Deep myometrial invasion
Cervical stromal invasion &
positive lymph nodes
Stage-IV d/s
Stage-II or III d/s with >2
risk factors:
 Cervical invasion
 Peritoneal cytology +ve
 +ve LN
 Non-endometroid histology

48. Prognostic variables
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
12)
13)
14)
LYMPH NODE
HORMONE RECEPTOR
PERITONEAL CYTOLOGY
HISTOLOGICAL GRADE
AGE
Age
ISTHMUS & CERVIX
METASTASIS &
LYMPH-VASCULAR SPACE
DNA PLOIDY
MYOMETRIAL INVASION
STATUS
Independent prognostic
EXTENSION INDEX
GENETIC/MOLECULAR
PROLIFERATIVE
TUMOR SIZE
INVASION
Histologic type
INTRAPERITONEAL
Dependent prognostic variable
Stronglyimp. Prognostic factor
variables
HISTOLOGICALprognosis
asso. with : TYPE
Strong predictor of
Most
TUMOR prognostic
Independentother asso.
Tumor <5grade better
mm from the
Histologic grade
If Younger age-is poor with:
asso. with MARKERS
Inc. tumorMETASTASIS
inDeterminesINVOVEMENT
Lymphatic the risk of
Independent dissemination
Proportion ofrisk factor
ADNEXAL Non-diploid
variableEndometroid subtype
serosal myometrial
prognostic surface- worse
Non stage recurrence
prognosis ca.
Deep
Tumor size
Lymphatic
early
15% inincreases with:chance
tumor early stagein
lymph node metastasis
Type I- Mutationinc.better
ERCorrelated with: lymph
prognosis Inc. riskis rate of
or PR
variablesinc. risk asso.
(10%)- +ve tumorOlder pts- More
invasion
Cx involvement recurrence
6 High predictor of : with:
times thereis of
Myometrial invasion
Strong >2cm.~of80-90% 5
Stage
Non/sup. Invasion-18%
prognosisRecurrence
node metastasis
of:PTEN risk ofextension
recurrence
Cervical
developingof nodal
High grade genes
Lack of spread
Lymphatic
& ß –catenin
Lympho-vascular space invasion yr chancesdifferentiationin
PRSignificantly asso. with
stronger 1
Distanttumor size
For everynode inc.
Lymph predictor
spread
Larger Distant in p53,
recurrent ca. yr. metastasis
Depth II- Mutation level
metastasisrecurrence of
dissemination
of absolute
Type themyometrial
Higher 7% recurrence of
survival rate in rate
Isthmus-cervix extension
age tumor recurrence
Local
5Diseaseinc.survival rate:
Deep free recurrence
yr.–
d/s
invasioninvasionthe survival
Lymphatic
p16, e-cadherin genes
Deep invasion- 60%
receptors better
Poor survival
recurrence metastasis
Distant 54%
Peritoneal cytology
Inc. risk of recurrence
+veprognosis
-ve- 90%
Adnexal involvement
Lymph node metastasis
Intra peritoneal tumor
Hormone receptor status
DNA ploidy/ proliferative index
Genetic/ molecular tumor marker

50. Principles of treatment
Uterus should be removed in all the
patients
 Pelvic LN metastasis is ~36% in Stage-II,
so protocol should include removal of them
 Chances of d/s spread outside the pelvis
(Para-aortic nodes, Adnexal structures &
upper abd.) is high, there should be
evaluation & treatment of extrapelvic
disease.


51. treatment
Exploratory laparotomy
Biopsy of any suspicious lesion
TAH-BSO
Peritoneal cytology
Resect any enlarged LN
Selective Pelvic & Para-aortic
lymphadenopathy

52. STAGE-IA
Tumor confined to corpus uterus, IA- No or <50% of myometrial
invasion
GRADE-1,2
No/minimal myometrial invasion
OBSERVE
OBSERVE
100% 5 yr disease free
survival rate
GRADE-2,Superficial myometrial invasion
GRADE-3,No myometrial invasion
VAGINAL
IRRADIATION

53. STAGE-IB
Tumor confined to corpus uteri, IB- >50% of myometrial invasion
GRADE-3, Any myometrial invasion
Deep myometrial invasion
PELVIC
RADIOTHERAPY
&
VAGINAL BOOST
Stage-I survival rate 5yr
87%

55. STAGE-II
Tumor invades cervical stroma, but does not extend beyond the
uterus
Cervix spread
Radiotherapy
PELVIC
RADIOTHERAPY
&
VAGINAL BOOST
Survival rate 5yr
76%
4500-5040 cGy.
5-6 wks
Vaginal boost
6000-7000 cGy

56. Positive peritoneal cytology
OBSERVE
OR
PROGESTINS

57. STAGE-III
Local &/or regional spread of tumor
IIIA- Serosa of uterus &/or adenexa
IIIB- Vaginal &/or parametrial involvement
IIIC- Pelvic (IIIC1) &/ or Para-aortic LN (IIIC2)
Eradication of all macroscopic disease
PELVIC
RADIOTHERAPY
&
VAGINAL BOOST
Paraaortic lymph node +ve- extended field/whole abdomen radiation
Survival rate 5yr
59%

58. GRADE-3, Any myometrial invasion
Deep myometrial invasion
Cervix, serosal, vaginal spread
Positive pelvic lymph nodes
-VE Para-Aortic
LN
PELVIC
RADIOTHERAPY
&
VAGINAL BOOST
+VE Para-Aortic
LN
EXTENDED FIELD
RADIOTHERAPY
4000-5000 cGy

59. STAGE-IV
Bladder &/or Bowel mucosa &/or distant metastasis
IVA- Bladder &/or Bowel mucosa
IVB- Distant metastasis
Eradication of all macroscopic disease
Partial Colectomy
Partial cystectomy
Post op
CHEMOTHERAPY
(Treatment of choice)
Survival rate 5yr
18%
+
WHOLE ABDOMEN
RADIATION
3000 cGy
with kidney
shielding
+
1500 cGy to
para aortic
LN
+
2000cGy to
pelvis

60. Algorithm for management
Patient with diagnosed endometrial cancer
Primary radiation
Pre op evaluation &
clinical staging
Surgical staging
Post op radiation
Evaluation of
prognostic factors
Close follow up
Selected therapy
(progesterone /
chemotherapy)

61. Follow up

History & Physical examination (Most effective method):
1st 2 yrs.- Every 3-4 mths
Then- Every 6 mths

Chest X-Ray:
Every year

CA-125: For patients :
Who have elevated CA-125 @ the time of diagnosis
Have extrauterine disease

63. Recurrent disease
~25% of the treated early endometrial cancer
recurs.
st
>50% recurs in 1 2
years
~75% recurs in 1st 3
years

64. Points to remember
Recurrence is less when the surgery is
combined with post op radiation therapy
Patient treated with surgery + radiation
generally do not have local or pelvic
recurrence but have extrapelvic mets.
M/C site for mets.- Lung, Abdomen, Lymph
nodes (Aortic, Supraclavicular, Inguinal),
Liver, Brain & Bone

65. Rates of recurrence
Rates of recurrence
Myometrial invasion
<50%
>50%
Lymph nodes
-ve
+ve
Cervical stromal invasion
Stage
IV disease
II/III disease & >2 risk
factors
I/II/III disease & < risk
factors
4%
28%
2%
31%
31%
63%
21%
1%

66. Factors affecting prognosis
Isolated vaginal recurrence
Initially well differentiated tumor
Recurrence after 3 years
Younger age of recurrence
Good
prognosis

67. Clinical features

68. Treatment
Isolated vaginal recurrence
External radiation
+
Brachytherapy
Pelvic recurrence
radiotherapy
+
Radical surgical resection
+
Intra op radiotherapy
Metastatic carcinoma
Combination
chemotherapy
Progestin therapy in case
of Progesterone receptor
+ve tumor

69. Incidental diagnosis
3 OPTIONS:
Factors which would guide:
observe
Risk of nodal/extrauterine
d/s
Reoperate for
surgical staging
Pelvic
radiotherapy
Tumor grade
Depth of invasion
Evidence of lymphadenopathy
on CT abd. or pelvis
Patient willingness

70. Lets see
the
mind power

71. Question 1
Factors which decreases the risk of endometrial
cancer?
a) Estrogen replacement therapy
b) Tamoxifen
c) Smoking
d) Poly cystic ovarian syndrome
e) Diabetes

72. Question 2
A lady is diagnosed of endometrial cancer
which is extending to the cervical stroma and
her pelvic lymph node biopsy came to be
+ve. In which stage you would like to keep
her?
a) Stage IA
b) Stage II
c) Stage IIIA
d) Stage IIIC

73. Question 3
A 50 yr old lady has been diagnosed of
having papillary serous carcinoma
endometrium and another lady is
diagnosed
of
having
mucinous
carcinoma. Both are in stage II. Which
lady is going to survive more after
therapy?

74. Question 4
In your OPD-8 if a post menopausal lady since
11yrs. gave history of spotting last night. After
history & examination you came to know that
there are no risk factors of endometrial
cancer & the cervix is also healthy but
atrophic. Now what you will do?
a) Ask her to get a TVS done
b) Ask her to come back if BPV recurs
c) Reassure her and give her estrogen cream for LA

75. Question 5
If a lady is diagnosed to have ca endometrium
which has spread to the endocervical glands.
Under which stage you would like to keep
her?
a) Stage IA
b) Stage IB
c) Stage II
d) Stage IIIA