Endometrial carcinoma

Objectives
Students will be able to describe:
Epidemiology of endometrial carcinoma
Risk factors and premalignant lesion i.e. endometrial
hyperplasia
Pathological types
Modes of spread
Clinical and surgical staging and grading
Clinical presentation
Investigations
Management modalities
Prognostic factors and survival
Introduction
Accounts for 3% of cancer in
females.
Fourth most common cancer in
women
USA- the most common female
genital tract malignancy.
India-third common female genital
tract malignancy
Epidemiology
Median age: 61 years
75-80% postmenopausal.
Geographical/racial variation:
white North Americans-highest
incidence.
Incidence high in affluent
industrialized countries.
Risk factors
Hormone dependent: estrogen
Risk factors : related to prolonged,
unopposed estrogen stimulation
of the endometrium
1. Obesity: peripheral conversion of
androgens to estrone in fat
tissue, 3 times high incidence in
women overweight by 21-50
pounds
Risk factors
2. Nulliparity: 2-3 times the risk
3. Infertility with irregular
anovulatory cycles
4. Late menopause: after 52 years
5. Functioning ovarian tumors:
granulosa cell tumor
6. Polycystic ovary syndrome
Risk factors
7. Estrogen replacement therapy in
postmenopausal women without
progestins: 4-8 times increased
risk
8. Use of anti-estrogen drug:
Tamoxifen
9. Diabetes mellitus,obesity,
hypertension: corpus cancer
syndrome
Pathology
Abnormal endometrial proliferation
Endometrial hyperplasia: premalignant
Risk of progression to carcinoma
depends on type of hyperplasia-
presence and severity of cytological
atypia.
Progestin therapy effective in reversing
EH without atypia, but less effective in
case of atypia.
 Classification of
endometrial hyperplasias
Type of hyperplasia Progression to cancer
(%)
Simple (cystic without 1
atypia)
Complex (adenomatous 3
without atypia)
Atypical
Simple (cystic with 8
atypia)
Complex
29
( adenomatous with
atypia)
Pathologic types
Endometrial adenocarcinoma: the
most common, from endometrial
glandular cells.
Endometrial stromal sarcomas:
less common-from stroma.
Mixed mullerian tumor: both
glandular and stromal elements,
rare.
Classification
1. Adenocarcinoma (endometrioid).
2. Adenocarcinoma with benign
squamous change
(adenoacanthoma).
3. Adenosquamous (mixed)
carcinoma.
4. Papillary serous adenocarcinoma.
5. Clear cell carcinoma.
6. Squamous cell carcinoma.
Pathology (contd..)
Localised raised, rough,
sessile or pedunculated lesion
often arise in the fundal region.
Myometrial invasion may be
obvious.
Mode of spread:

Direct- infiltration of myometrium,

serosa,parametrium, peritoneal
cavity, cervix, tubes, ovaries
Lymphatic- pelvic, para-aortic
lymph nodes,tubes, ovaries,
vagina
Hematogenous- late lungs, liver,
brain, bone.
Lymphatic spread
Staging
Clinical staging (FIGO, 2. exploration of the
1971) for patients not abdominal and pelvic
suitable for surgery. cavity with biopsy or
Surgical staging excision of any
(FIGO), 1988)- surgical extrauterine lesions
procedure should suggestive of
include metastasis,
1. sampling of peritoneal 3. hysterectomy,
fluid for cytologic 4. bilateral salpingo-
evaluation, oophorectomy,
5. removal of any
suspicious pelvic and
para-aortic lymph nodes
Grading (FIGO, 1989)
Differentiation of carcinoma expressed
as its grade, determined by
architectural growth pattern and nuclear
features.
G1: <5% nonsquamous or nonmorular
growth pattern
G2: 6-50% nonsquamous or nonmorular
growth pattern
G3: >50% nonsquamous or nonmorular
growth pattern
Grading
1988 FIGO surgical staging
for endometrial carcinoma
Stage Ia G123 Tumor limited to
endometrium
Ib G123 invasion to less than
one-half of the
myometrium
Ic G123 Invasion to more
than one-half of the
myometrium
Surgical staging (contd..)
Stage II a G123 Endocervical glandular
involvement only
II b G123 Cervical stromal
invasion
 Stage III a G123 Tumor invades serosa
and/or adnexa and/or
positive peritoneal
cytology
III b G123 Vaginal metastases
III c G123 Metastases to pelvic
and/or para-aortic lymph
nodes
Surgical staging (contd..)
Stage IV a G123 Tumor invasion
of bladder and/or
bowel mucosa
IV b Distant metastases
including intra-
abdominal and/or
inguinal lymph nodes
1971 FIGO clinical
staging for endometrial
carcinoma Stage I cases should be
subgrouped with regard
Stage 0- Carcinoma to the histologic grade of
in situ the adenocarcinoma as
follows:
Stage I- The Grade 1- highly
carcinoma is differentiated
confined to the adenomatous carcinoma.
corpus. Grade 2- moderately
Ia- The length of the differentiated
adenomatous carcinoma
uterine cavity is 8 with partly solid areas.
cm or less. Grade 3- predominantly
Ib- The length of the solid or entirely
uterine cavity is undifferentiated
carcinoma.
more than 8 cm.
Clinical staging (contd..)
Stage II The carcinoma has involved
the corpus and the cervix but has not
extended outside the uterus.
Stage III The carcinoma has extended
outside the uterus but not outside the
true pelvis.
Clinical staging (contd..)
Stage IV- The carcinoma has extended
outside the true pelvis or has obviously
involved the mucosa of the bladder or
rectum. A bullous edema as such does
not permit a case to be allocated to
stage IV.
IV a- spread of the growth to adjacent
organs.
IV b- spread to distant organs.
Screening
No effective screening method.
1. Endometrial sampling- various
methods: endometrial aspiration,
brush, lavage, aspiration
curettage, biopsy
Screening (contd)
2. Pap smear- pick up rate about
50%
3. Transvaginal ultrasound-
endometrial thickness >5mm
in postmenopausal woman
needs further evaluation.
Clinical features
Postmenopausal bleeding: the
most common presenting
symptom. (10-20% risk of having a
genital cancer)
Irregular and excessive bleeding:
in case of premenopausal women.
Abnormal, offensive, watery p/v
discharge.
Clinical features (contd)
Hematometra, pyometra
Pelvic discomfort and pain
<5% -asymptomatic.
Abnormal perimenopausal and
postmenopausal bleeding should
always be suspected and
investigated no matter how
minimal or nonpersistent.
Physical examination:
cachexia, pallor, obesity,
hypertension, peripheral lymph
nodes, abdominal mass, ascites
P/s : cervix healthy unless
involved by growth, bleeding or
purulent offensive discharge
through os
Physical examination
(contd):
Bimanual examination: uterus
atrophic, normal size or
enlarged, mobility restricted in
late stages.
Diagnostic investigations
Endometrial Biopsy for
histopathology: may be obtained
by various procedures
1. Endometrial biopsy with
suction/aspiration(OPD procedure
without general anesthesia)
2. Diagnostic Dilatation and Curettage
3. Fractional curettage/ examination
under anesthesia:
Fractional curettage
i. Endocervical curettage followed
by
ii. assessment of length of uterine
cavity using a uterine sound
iii. Dilatation of the cervical os
iv. Curettage of endometrial cavity
v. Specimens should be sent
separately.
Investigations (contd)
2. Hysteroscopy: extent of lesion, biopsy
under direct vision. But chance of
spreading more
3. Imaging: Ultrasonography, CT, MRI
4. Other investigations to assess the
patient before treatment: Hb%, blood
group, urinalysis, RFT, LFT, Blood
Sugar, X-ray chest, ECG, cystoscopy
etc.
Differential diagnosis of
postmenopausal bleeding
1. Endometrial atrophy
2. Estrogen replacement
therapy
3. Endometrial polyps
4. Endometrial hyperplasia
5. Cancer of the cervix
Prognostic factors
Age: Younger age better prognosis
Stage
Histologic type: nonendometrioid types,
clear cell carcinoma, serous papillary
type poor prognosis
Histologic grade: grade 3 , high
recurrence rate. Myometrial invasion
Lymph-vascular space invasion
Prognostic factors
(contd)
Isthmus-cervix extension
Adnexal involvement
Peritoneal cytology
Lymph node metastasis
Tumor size
Hormone receptor status: estrogen and
progesterone receptor +ve tumor-
better prognosis
DNA ploidy: aneuploid worse prognosis
Treatment
Treatment modalities:

Surgery
radiotherapy

combined

chemotherapy
Treatment of Stage I

Total abdominal hysterectomy with bilateral

salpingo-oophorectomy: peritoneal washing to
be taken, liver, omentum, adnexa, lymph
nodes should be thoroughly evaluated
Depth of myometrial invasion should be
assessed after removal of uterus. Frozen
sections of specimens including lymph nodes .
Post operative Radiotherapy: not needed if
the tumor is grade 1 and no myometrial
invasion. In all other cases of stage I tumors
postoperative vault irradiation should be given
Treatment (contd..) Stage
II

Involvement of cervix
Radical (Wertheims) hysterectomy

removal of:
1. Uterus with cervix,
2. Fallopian tubes,
3. upper third vagina,
4. parametrial tissue,
5. uterosacral & uterovesical ligaments,
6. parametrial, obturator, internal & external iliac
lymph nodes.
Postoperative radiotherapy
Stage III

Radiotherapy

Laparotomy with removal of as

much tumor as possible (Debulking
surgery)
Treatment (contd..)
Stage IV
Individualized management, with

primary aim being control of

symptoms and local control of
tumor growth

Radiation therapy, cytotoxic drugs

and hormonal therapy.
Treatment (contd..)
Adjuvant progestogen therapy: in
persistent or recurrent
cases.Medroxyprogesterone
acetate (Depot Provera),
hydroxyprogesterone hexanoate
Chemotherapy: adriamycin,
cisplatin, doxorubicin,
cyclophosphamide. Doubtful
benefit.
Five year survival

Stage 5-year survival

(%)
I 72.3
II 56.4
III 31.5
IV 10.5
Important Questions
What is the premalignant lesion of endometrial
carcinoma and its classification ?
Describe the risk factors for endometrial
carcinoma.
Describe the clinical presentation of
endometrial cancer.
How would you confirm the diagnosis of
endometrial cancer?
Describe the clinical and surgical staging of
endometrial cancer.
What are the factors determining the prognosis of
endometrial cancer?