• Endometrial hyperplasia is defined
as an increased proliferation of
endometrial glands, relative to
stroma resulting in increased gland
to stromal ratio than normal
• The proliferative glands vary in size
& shape and may shows cytological
atypia, which may progress or co-
exist with endometrial carcinoma.
Peri-menopausal women, if
estrogen level more than
Causes of endometrial hyperplasia :
Endometrial hyperplasia associated with prolonged
estrogen stimulation of the endometrium, which may be
2. Increased estrogen production from endogenous
source or exogenous estrogen.
4. Polycystic ovarian disease
5. Functional granulosa cell tumors of ovary
6. Estrogen replacement therapy
7. Cortical stromal hyperplasia
Molecular genetics :
Mutation in PTEN genes ( 20% of
According to architectural &
cytological factors endometrial
hyperplasia divided into four groups-
1. Simple hyperplasia
2. Complex hyperplasia
3. Atypical hyperplasia ( has more
change to developed malignancy )
Simple hyperplasia :
Glands are various size and irregular
shapes with cystic dilatation with mild
hyperplasia. Epithelial growth pattern
and cytology are similar to those of
proliferative endometrium.Mitosis are
1% chance of develop carcinoma.
Complex hyperplasia :
Increase in the number and size of the
glands, marked gland crowding and
branching occurs. Gland form finger
like projection but not invasion
towards stroma, epithelial cell
remains cytologically normal.
3% chance to develop carcinoma .
Atypical hyperplasia :
In simple atypical hyperplasia, there is
cytological atypia within the
glandular cells- such as loss of
polarity, vesicular nuclei, prominent
nucleoli, cells become rounded and
loss the normal perpendicular
orientation to the basement
8% may progress to carcinoma.
In complex atypical hyperplasia
consists of back-to-back crowding of
glands lined by atypical cells. Lipid
laden “ foam” cells may be noted in
the intervening stroma.
23% to 48% women have the chances
to develop carcinoma.
Endometrial carcinoma is the most
common invasive cancer of the
female genital tract.
It is about 7% of all invasive cancer in
• Common in women >40 years of
age ( peri & post menopausal
• Relatively unknown in young age.
• Peak incidence 55 to 65 years of
Risk factor of endometrial carcinoma :
5. Unopposed estrogen stimulation
6. Family history
7. Endometrial atrophy
A. According to the clinico-
pathological & molecular studies :
1. Type - I
2. Type - II
B. According to the
1. Endometroid adenocarcinoma
2. Adenocarcinoma with squamous
3. Adenosquamous carcinoma
4. Serous carcinoma
5. Clear cell carcinoma
Type - I endometrial carcinoma :
It is the most commonest type, about
80% of all cases. Usually occurs in 55-
65 years. The majority are well
differentiated and estrogen related,
present histologically as a
endometroid tumor associated with
atypical endometrial hyperplasia.
Prognosis is better and have
superficial myometrial invasion.
Molecular genetics of Type-I :
1. Mutation in PTEN tumor suppressor
gene – 80%
2. PIK3CA mutation – 39%
3. Mutation in KRAS & beta catenin
4. Mutation in KRAS gene
5. Mutation in p53 gene ( upto 50% in
poorly differentiated endometroid
Type – II tumor :
About 15% of endometrial carcinoma.
It is arise in the sitting of endometrial
atrophy. Not related to estrogen
stimulation or endometrial hyperplasia.
They are poorly differentiated, high
grade tumor with poor prognostic cell
type like - serous endometrial
carcinoma, clear cell tumor.
Usually occurs in older or post
menopausal women and not related
to obesity, HTN, DM.
Develop finger like papillary
Aggressive in behavior.
Molecular genetics of Type-II :
1. Mutation in p53 gene
Endometroid carcinoma :
85% of endometrial carcinoma.
Endometrial carcinoma either localized
polypoid tumor or diffuse tumor
involving the endometrial surface.
Endometrial adenocarcinoma formed
well differentiated to poorly
differentiated glandular structure mixed
with solid sheet of malignant cells. Poorly
differentiated type have barely
recognizable glands and greater degree
of nuclear atypia and mitotic activity.
Upto 20% of endometroid carcinoma
contain foci of squamous differentiation.
Generally arise in the sitting of small
atrophic uterus, often form large bulky
tumor or deep invasion in to the
The precursor of serous carcinoma is
endometrial intraepithelial carcinoma.
• Lesion may have papillary growth
pattern composed of cells with marked
cytological atypia, including high nuclear
to cytoplasmic ratio, atypical mitotic
figure,heterocromastia and prominent
• They can also have predominantly
glandular pattern, different from
adenocarcinoma by marked cytological
Malignant mixed mullarian tumor :
MMTs consist of endometrial
adenocarcinomas with malignant changes
in the stroma.The stroma tends to
differentiate into a verity of malignant
mesodermal components, including
muscle, cartilage and even osteoid.
MMTs occur in the post-menopausal
women and present with post menopausal
bleeding. This is a highly malignant tumor.
In gross appearance: MMTs are
fleshier than adenocarcinomas, may
be bulky and polypoid and sometimes
protrude through the cervical os.
On histology: the tumor consist of
adenocarcinoma mixed with
The step-grading system applied to
endometroid tumor –
G1 : Well differentiated adenocarcinoma,
less than 5% solid growth.( with easily
recognizable glandular pattern )
G2 : Moderately differentiated
adenocarcinoma with partly solid
growth <50% ( showing well formed
glands mixed with solids sheets of
malignant cells .
G3 : Poorly differentiated adenocarcinoma
with predominantly solid growth >50%
( solid sheets of cell with barely
recognizable gland with greater degree
of nuclear atypia and mitotic activity )
All non-endometroid carcinoma classified
as grade-3 irrespective of histological
Stage I :Carcinoma is confined to the corpus
Stage II :Carcinoma involves the corpus and
Stage III :Carcinoma extends outside the true
but not outside the true pelvis.
Stage IV :Carcinoma extends outside the
true pelvis or involves the mucosa of
the bladder or rectum.
Route of spread :
1. Direct spread
2. Lymphatic spread and
3. Heamatogenous spread
How to diagnosed :
1. Pelvic examination
3. Pap’s smear
4. Endometrial sampling
5. D & C
1. Anemia may result, caused by
chronic loss of blood.( This may occur if
the women has ignored symptoms of
prolonged or frequent abnormal menstrual
2. Perforation of the uterus may occur
during D & C or an endometrial biopsy.
Surgery and Radiation therapy are the
only methods of successful
Women with the early stage-I disease
treatment with surgical hysterectomy
either abdominal or vaginal.
Women with late stage-I disease and
stage-II disease are often offered
surgery in combination with Radiation
Stage-I & well differentiated
endometrial carcinoma – 75% to 80%
Stage-II & III : < 50% prognosis
1. All women should have regular
pelvic examination and pap’s smear
( beginning at the onset of sexual
activity or at the age of 20 if not
sexually active ) to help detect signs
of any abnormal development.
2. Women with estrogen replacement
therapy should report immediately to the
doctor if any of the following symptoms
I. Bleeding or spotting after intercourse
II. Bleeding that lasts longer than 7 days
III. Reappearance of blood or staining
after 6 months or more of no
bleeding at all.