1. Under supervision of :
Dr/Nahed Hussein
Dr/Hanan Abd Elmenam
Prepared by:
Esraa Mohamed Khalil (6010).
Esraa Mohamed Abd el Aaty(6011).
Esraa Mohamed Mahmoud(6012).
2. Definiton:
Malignant change of the endometrial lining of the uterine
cavity
Incidence
Endometrial cancers are the most common gynecologic
cancers
*Over 35000 women are diagnosed each year
*The incidence is on a slow rise secondary to the obesity
epidemic.
*The most common subtype, endometrioid
adenocarcinoma,
Epidemiology
It's the most frequent cancer occurring in the female
genital tract.
It appears most frequently between ages of 55 and 65, and
uncommon below 40. There are two pictures of this
disease, perimenopausal women with estrogen excess and
in older women with endometrial atrophy.
3. Risk factors:
The cause endometrial cancer isn't known exactly. But there are
some factors that might increase or reduce the risk of developing it
Many of the risk factors for endometrial cancer relate to the
body’s exposure to the female sex hormone, oestrogen. Or to the
balance between types of the two female sex hormones, oestrogen
and progesterone.
Oestrogen without progesterone to balance it increases the Risk of
cancer.
cancer is much more common in women after the menopause as
the body stops making progesterone after the menopause, but still
produces a small amount of oestrogen.
1-Age
It occurs most commonly in women between the ages of 60
and 79.
Most women diagnosed with endometrial cancer have had
their menopause
Only 5% of cases are diagnosed in women under 40years old. But
women who have a particular gene fault called HNPCC are more
likely than the general population to develop it at a younger age.
2- Obesity
Obesity increases the risk of incidence of endometrial
cancers. This because obese women have higher levels of
oestrogen As
4. a) Adipose tissue convert certain hormones into
oestrogen and this lead to endometrium builds up.
And more lining (endometrial) cells are produced,
there is a greater chance of one of them becoming
cancerous.
b) Sometimes obesity cause insulin resistance that
lead to i ncrease level of insulin that can stimulate
cancerous growth in the lining of the endometrium.
3-Diabetes and high blood pressure
Diabetes and high blood pressure are both linked to
being overweight and so may be connected with womb
cancer for that reason.
4- Infertility and Nulliparity
Having 3 or more children your could be lowered the
risk by up to two thirds.
Oestrogen levels are low and progesterone levels are
high in pregnancy.
Unopposed oestrogen increases the risk of womb cancer.
5-Menstrual history
Some factors linked with menstruation can increase risk of
womb cancer as they cause higher levels of oestrogen.
Examples are
Pre and post menopausal bleeding
Infertility due to failure of the ovaries
5. Early menarche
Late menopause
anovulatory cycles
Amenorrhea
Menorhagia
6-Endometrial hyperplasia
Endometrial hyperplasia is a benign condition where the
lining of the womb becomes thicker.
Symptoms of endometrial hyperplasia are
Menorrhagia.
Metrorrhagia.
post menopausal bleedin
7-Polycystic ovary syndrome(PCOS)
Women with PCOS have a hormone imbalance which
may cause very irregular periods. They are also more
likely to be insulin resistant, overweight, and have
diabetes. Most women (more than 90%) who
have PCOS do not develop womb cancer.
8-Family history and other cancers
Past history of cancer of the colon, rectum or
breast increased risk of getting womb cancer.
Similarly, once having womb cancer, there is increased
risk of developing certain other cancers.
6. Having a family history womb cancer double the
risk of its incidance
9-DRUGS
a) Tamoxifen and raloxifene
An increased risk of womb cancer is a known side
effect of taking tamoxifen, which is a hormonal
therapy for breast cancer. has a similar effect on
the womb to oestrogen. It occure after taking
tamoxifen for more than 2 years .
Raloxifene, another hormonal treatment for breast
cancer, has also been shown to increase womb
cancer risk in one study. But another study showed
a reduction in womb cancer risk in women who took
raloxifene.
b) HORMONE REPLACEMENT THERAPY (HRT)
Hormone replacement therapy is used by many women to
control the symptoms of menopause. There are different
types of HRT. Oestrogen only HRT increases the risk of
womb cancer and is normally only prescribed to women
who have a hysterectomy.
Some studies show a small reduction in risk of womb
cancer in women taking continuous combined HRT .
normal weight women taking continuous combined HRT
for 10 years or longer had an increased risk of womb
cancer.
7. c) CONTRACEPTIVE PILLS
Most types of birth control pills used today normally
decrease the risk of womb cancer. These contain either a
combination
of
oestrogen
and
progesterone
(combination pills), or progesterone only (mini pills).
10-CHEMICALS AS (TALCUM POWDER)
Regular use of talcum powder in the genital area may
increase the risk of womb cancer.
11-Diet and alcohol
Diet only seems to play a small role in in womb cancer.
Eating a high fat diet may causr a high risk of
developing womb cancer either directly or by obesity
making.
12-PHYSICAL ACTIVITY
Physically active women have a reduced risk of womb
cancer who are more.
13-Ethnicity
White women have a greater chance of developing womb
cancer than black women But if black women do get
womb cancer, these cancers are more likely to be faster
growing tumours
8. Classification
1-Carcinoma
Most endometrial cancers are carcinomas (usually
adenocarcinomas), meaning that they originate from the
single layer of epithelial cells that line the endometrium
and from the endometrial glands.
endometrial carcinomas are classified into two pathogenic:
Type I:
These cancers occur most commonly in pre- and perimenopausal women, often with a history of unopposed
estrogen exposure and/or endometrial hyperplasia.
They are often minimally invasive into the underlying
uterine wall, are of the low-grade endometrioid type, and
carry a good prognosis
Type II:
These cancers occur in older, post-menopausal women,
are more common in African-Americans, are not associated
with increased exposure to estrogen, and carry a poorer
prognosis. They include
the high-grade endometrioid cancer
the uterine papillary serous carcinoma
the uterine clear cell carcinoma
FIGO grading of Endometrial Carcinoma
G1: Highly differentiated (composed of glands and 5%
of lesion is of solid growth pattern)
G2: Moderately differentiated ( 6%-50% of lesion
composed of solid sheets of cells).
G3: Undifferentiated ( > 50% of lesion composed of
solid sheets of cells.
9. 2-Sarcoma
In contrast to endometrial carcinomas the uncommon
endometrial stromal sarcomas are cancers that originate in
the non-glandular connective tissue of the endometrium
3- Uterine carcinosarcoma, ( Malignant mixed müllerian
tumor): is a rare uterine cancer that contains cancerous
cells of both glandular and sarcomatous appearance.
STAGING Of endometrial carcinoma
Endometrial carcinoma is surgically staged using the
FIGO cancer staging system
IA: Tumor confined to the uterus, no or < ½
myometrial invasion
IB: Tumor confined to the uterus, > ½ myometrial
invasion
II :Tumor involves the uterus and the cervical stroma
IIIA: Tumor invades serosa or adnexa
IIIB :Vaginal and/or parametrial involvement
IIIC1: Pelvic lymph node involvement
IIIC2: Para-aortic lymph node involvement, with or
without pelvic node involvement
IVA: Tumor invasion bladder mucosa and/or bowel
mucosa
IVB: Distant metastases including abdominal
metastases and/or inguinal lymph node.
10. Clinical picture:
SYMPTOMS
1-COMMON SYMPTOMS
The most common symptom of Endometrial cancer is:
Abnormal vaginal bleeding from the– especially after
menopause
About 90% of womb cancer cases are discovered as
irregular vaginal bleeding which may be.
Post menopausal bleeding, which is a key symptom of
womb cancer in most cases.
Metrorrhagia: in premenopausal women in women older
than 40: extremely long, heavy, or frequent episodes of
bleeding (may indicate premalignant changes).
Vaginal discharge –( from pink and watery to dark
and foul smelling)
Only a small number of women with dysfunctional uterine
bleeding will actually have womb cancer.
2-LESS COMMON SYMPTOMS
Less common symptoms of womb cancer can include
a) Lower abdomenal Pain or discomfort
b) Dysparonia .
3-SYMPTOMS OF ADVANCED ENDOMETRIAL CANCER
11. Advanced womb cancer can cause more symptoms,
especially if the cancer has spread to other parts of the
body.
These are much less common and can include:
Loss of appetite and weight
Tiredness or weakness
Feeling or being sick
Constipation
Polyurea
Back pain or leg pain.
Signs
a) General examination
To asses general condition for anemia, caused
loss of blood.
To detect distant metastasis.
b) Abdominal examination
Palpate liver for metastasis
Supra pubic region for large pyometra
c) Local examination (not characteristic)
Bimanual examination: the uterus may be
-normal sized
-Slightly smaller in size(post menopausel atrophy)
by chronic
12. Investigation of Endometrial cancer:
1.Sampling endometrial tissue:
To find out whether endometrial
endometrial cancer is present.
hyperplasia
or
2.Endometrial biopsy:
Is very accurate in postmenopausal women.
3.Hysteroscopy
This is usually done with the patient awake, using a local
anesthesia . it allows the direct visualization of the uterine cavity
and can be used to detect the presence of lesions or tumours. It
also permits to obtain cell samples with minimal damage to the
endometrial lining (unlike blind D&C)
4.Dilation and curettage (D&C)
If the endometrial biopsy sample doesn't provide enough
tissue, or if the biopsy suggests cancer but the results are
uncertain, a D&C must be done.Then looked at under the
microscope to see whether cancer is present.
6.Transvaginal ultrasound or sonography
to evaluate the endometrial thickness in women with
postmenopausal bleeding is increasingly being used to
evaluate for endometrial cancer..
7.Cystoscopy and proctoscopy These procedures now are
rarely used for endometrial cancer.
13. 8.Computed tomography (CT)
CT scans are not used to diagnose endometrial cancer.
However, they may be helpful to see whether the cancer
has spread to other organs and to see if the cancer has
come back after treatment.
10.Magnetic resonance imaging (MRI)
MRI scans may be a good way to tell how far the
endometrial cancer has grown into the body of the uterus.
MRI scans may also help find enlarged lymph nodes.
11.Positron emission tomography (PET):
In this test radioactive glucose is given to look for cancer
cells. But their role is still being studied.
12.CHEST X-RAY:
This test can show whether the cancer has spread to the
lungs. It may also be used to look for serious lung or heart
problems, especially before surgery.
13.Blood tests:
A. Complete blood count.
B. CA 125 blood test.
CA 125 is a substance released into the bloodstream by
many endometrial and ovarian cancers. In someone with
endometrial cancer, a very high blood CA 125 levelsuggests
that the cancer has probably spread beyond the uterus
14. Pathology
The histopathology of endometrial
cancers is highly diverse. The
most common finding is:
a well-differentiated
endometrioid adenocarcinoma,
which is composed of numerous,
small, crowded glands with
varying degrees of nuclear atypia,
Endometrial adenocarcinoma
mitotic activity, and stratification.
This often appears on a background of endometrial
hyperplasia.
Frank adenocarcinoma may be distinguished from atypical
hyperplasia by: the finding of clear stromal invasion, or
"back-to-back" glands which represent non destructive
replacement of the endometrial stroma by the cancer.
With progression of the disease, the myometrium is
infiltrated.
However, other subtypes of endometrial cancer exist and
carry a less favorable diagnosis such as the uterine
papillary serous carcinoma and the clear cell carcinoma
15. Treatment (according to stage):
Stage 1: (the commonest):
1_If the patient is unfit for surgery: only radiotherapy is
used(internal,external)the results is inferior to surgery.
2_If the patient is fit for surgery:combined surgery and
radiotherapy.
a .1st step is panhysterectomy
(total abdominal hysterectomy*TAH*, with bilateral
salpingo-oophorectomy *BSO*) and removal of a cuff
from upper vagina.
b.Then surgical staging :
-If G1 or G2,no myometrial invasion ,no isthmic
invasion with-ve peritoneal cytology:No further
treatment is required.
-If G1 or G2 and myometrial invasion by <50% :
Only post operative internal radiation into the vaginal
vault with radium to decrease local recurrence.
-If G3 or myometrial invation by >50% (L.N spread) :
Post operative external radiation to the whole pelvis and
internal radiation to the vaginal vault.
16. Stage 2 :
-Radiotherapy or wertheim’s operation.
-Recently it is treated as stage 1(panhysterectomy and post
operative irradiation) as these female are very risky for
wertheim’s operation (old,obese,hypertensive,diabetic).
Stage 3:
-Surgery (T.A.H. and B.S.O.) then followed by post
operative radiotherapy and intraperitoneal phosphorus 32
(for +ve peritoneal cytology).
-If clinically detected : treatment should be preceded by
pre-operative radiotherapy.
Stage 4 and recurrent cases:
1.Palliative radiotherapy:
.Brachytherapy and external radiation.
SIDE EFFECTS OF RADIATION THERAPY
-Short-term side effects: tiredness, upset stomach, or loose
bowels. Serious fatigue,diarrhea,nausea and vomiting.Skin
changes are also common,this ranging from mild
temporary redness to permanent discoloration. The skin
may release fluid, which can lead to infection.
Radiation can cause cystitis, proctitis, vaginitis, anemia
and leukopenia.
17. -Long-term side effects: vaginal dryness. In some cases
scar tissue can form in the vagina causing vaginal stenosis
which can make vaginal intercourse painful,
lymphedema,osteoporosis.
Pelvic radiation therapy can damage the ovaries, resulting
in premature menopause.
2.Palliative chemotherapy :
Combination chemotherapy sometimes works better than
one drug alone in treating cancer.
Drugs used in treating endometrial cancer may include:
Paclitaxel (Taxol®)
Carboplatin
Doxorubicin (Adriamycin®)
Cisplatin
The most common combinations include carboplatin with
paclitaxel and cisplatin with doxorubicin.
For carcinosarcoma, the chemo drug ifosfamide, either
alone or in combination with either carboplatin, cisplatin
or paclitaxel, is often used.
Side effects of chemotherapy
Side effects of chemotherapy depend on the specific drugs,
the amount taken, and the duration. Common side effects
include:
Nausea and vomiting.
18. Loss of appetite.
Mouth and vaginal sores.
Hair loss.
.Anemia and leukopenia.
3. Hormonal treatment:
A. .PROGESTINS
The main hormone treatment for endometrial cancer uses
progesterone-like drugs called progestins. The 2 most
commonly used progestins are medroxyprogesterone
acetate and megestrol acetate.These drugs work by
slowing the growth of endometrial cancer cells. Side effects
can include increased blood sugar levels in patients with
diabetes. Hot flashes, night sweats, and weight gain also
occur.
B. .TAMOXIFEN
Tamoxifen, an anti-estrogen drug often used to treat breast
cancer, may also be used to treat advanced or recurrent
endometrial cancer. The goal of tamoxifen therapy is to
prevent any estrogens circulating in the woman's body from
stimulating growth of the cancer cells. It can cause hot
flashes and vaginal dryness.There is increased risk of
serious blood clots in the leg. (80 % of endometrial
adenocarcinoma are estrogen dependant).
19. C. .Gonadotropin-releasing hormone agonists:
Gonadotropin-releasing hormone (GNRH) agonists are
another way to lower estrogen levels in women with
functioning ovaries.Side effects can include any of the
symptoms of menopause, such as hot flashes and vaginal
dryness. If they are taken for years, these drugs can
leading to osteoporosis.
D..AROMATASE INHIBITORS :
can stop estrogen from being formed in fat tissue and lower
estrogen levels. Examples of aromatase inhibitors include
letrozole (Femara), anastrozole (Arimidex). These drugs
are most often used to treat breast cancer, but may be
helpful in the treatment of endometrial cancer. Side effects
can include joint and muscle pain as well as hot flashes. If
they are taken for years, these drugs can cause
osteoporosis. These drugs are still being studied for use in
treating endometrial cancer.
4. Pain reliever.
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