Malignant diseases of uterus

Endometrial cancer
Incidence
Endometrial cancer is the most common gynecological malignancy affecting UK women with
an incidence of 95 per 100,000 women. The mean age of diagnosis is 62 years, although
cancers can be diagnosed in women throughout their reproductive life. Approximately 25% of
endometrial cancers occur before the menopause.
Classification Of Endometrial cancer
1. Type 1 tumours are endometrioid adenocarcinomas that are oestrogen driven and arise
from a background of endometrial hyperplasia.
2. Type 2 tumours include high-grade serous and clear cell histological subtypes and arise
from an atrophic endometrium.

Etiology
The risk factors for type 1 endometrial cancer are well established. Most of these reflect an
increased lifetime exposure to oestrogen. Oestrogen causes endometrial cells to proliferate
when it is unopposed by progesterone. Therefore, hyperoestrogenic states increase
endometrial cancer risk, while cyclical or continuous progestin-containing hormone
treatments reduce risk.
Factors that increase endometrial cancer risk
1. Nulliparity.
2. Late menopause above 52.
3. Unopposed estrogen therapy.
4. Obesity: Obese women are at risk of endometrial cancer because they are more likely to
have anovulatory menstrual cycles and less likely to get pregnant. Furthermore, the
aromatization of androgens to oestrogen by adipose tissue provides a continuous
postmenopausal supply of oestrogen.
5. Diabetes: insulin and insulin-like growth factor stimulate endometrial proliferation,
which is why endometrial cancer is more common in diabetic women.
 6. Tamoxifen therapy: a selective oestrogen receptor modulator (SERM) used to prevent
recurrent breast cancer, which is antioestrogenic in the breast but stimulatory in the
endometrium. New generation SERMs, such as raloxifene, have a lesser effect on the
Selective estrogen receptor modulators

endometrium.
7. Family history: The most common association is with Lynch syndrome, an autosomal
dominant condition. The lifetime risk of endometrial cancer in women with Lynch
syndrome is 40–60%. Other tumour associations include colorectal, ovarian and
urothelial tumours. Women with Lynch syndrome are offered prophylactic
hysterectomy following completion of childbearing.
Factor that protect against endometrial cancer
1. Hysterectomy.
2. Combined oral contraceptive pills.
3. Progesterone based contraception including injectables.
4. Intrauterine device including cu-IUD and LNG-IUS.
5. Pregnancy.
6. Smoking.
Clinical features Of Endometrial cancer
1. Postmenopausal bleeding (PMB): approximately 5–10% of women with PMB have an
underlying gynecological malignancy and this ‘red flag’ symptom should always be
investigated.
2. Abnormal bleeding is the most common presenting complaint in premenopausal women
too, who variously complain of heavy, irregular or intermenstrual bleeding (IMB).
3. Women at more advanced stages of disease present with abdominal pain, urinary
dysfunction, bowel disturbances or respiratory symptoms.
4. Sometimes endometrial cancer is picked up incidentally on a cervical smear, which
shows ‘abnormal glandular cytology’.
5. Signs of endometrial cancer include bleeding from the cervical os on speculum
examination and a bulky uterus on bimanual pelvic examination. In most women with
endometrial cancer, however, pelvic examination is completely normal.
Diagnosis and investigation of PMB
The mainstays of diagnosis are TVUSS, hysteroscopy and endometrial biopsy. TVUSS allows a
quick and accurate assessment of endometrial thickness. If the endometrium measures less
than 4 mm, cancer is very unlikely and further investigation is not needed. Any measurement
greater than this requires further evaluation by hysteroscopy and/or biopsy.
Hysteroscopy is performed in the outpatient setting under local anaesthetic where possible. A
general anaesthetic is required in patients with cervical stenosis or where hysteroscopy is
poorly tolerated.
The histology report describes the type (endometrioid or other histological subtype) and grade
of tumour. Complex hyperplasia with atypia is a premalignant condition that frequently
coexists with low-grade endometrioid tumours of the endometrium. The risk of progression to
endometrial cancer is 25– 50%.
Staging
The extent of disease (stage) is determined by magnetic resonance imaging (MRI) scan and
FIGO staging uses this information. Patients with high-grade tumours undergo a computed
tomography (CT) scan of the chest, abdomen and pelvis to exclude distant metastases.

International Federation of Gynecology and Obstetrics (FIGO) staging of carcinoma of the

uterus

I Confined to uterine body

IA Less than 50% invasion
IB More than 50% invasion
II Tumour invading cervix
III Local or regional spread of tumour
IIIA Invades serosa of uterus
IIIB Invade vagina and/or parametrium
IIIC Metastases to pelvic and/or para-aortic LN
IV Tumour invade bladder, bowel and distant metastasis
Management
Surgery
Surgery is the mainstay of treatment for endometrial cancer. The extent of surgery depends
on several factors including grade and stage of disease, and the patient’s comorbidities.
Standard surgery is total hysterectomy and removal of both fallopian tubes and ovaries
(bilateral salpingo-oophorectomy). This can be performed abdominally or laparoscopically
(total, vaginally assisted or robotically).
If the MRI suggests cervical involvement, a modified radical hysterectomy is performed, which
also removes a cuff of vagina, paracervical and parametrial tissue to ensure adequate excision
margins. If the tumour is high grade (grade 3) or of type 2 histology, many centers perform
pelvic and para-aortic node dissection because nodal disease (to either pelvis or para-aortic
lymph node chains) is seen in one-third of patients.

Adjuvant treatment
Postoperative radiotherapy reduces local recurrence rate but does not improve survival.
Different units treat following surgery or only treat if the cancer recurs. Strategies include local
radiotherapy to the vaginal vault over a short period of time (brachytherapy) for local disease,
or brachytherapy combined with external beam radiotherapy for locally advanced disease
(stage III).
Chemotherapy is given for advanced or metastatic disease, although there is currently little
evidence to support its use.
Hormone treatment
Some women are not fit for surgery and others wish to avoid it for fertility-sparing reasons.
Treatment with high-dose oral or intrauterine progestins is successful for some women with
complex atypical hyperplasia and low-grade stage IA endometrial tumours, but relapse rates
are high.
Prognosis
The overall 5-year survival rate for endometrial cancer is 80%, although this varies depending
on tumour type, stage and grade of tumour.
Adverse prognostic features include advanced age, grade 3 tumours, type 2 histology, deep
myometrial invasion, lymphovascular space invasion, nodal involvement and distant
metastasis.
stage 5-years survival (%)
I 88
II 75
III 55
IV 16

Sarcoma of uterus
These are rare tumours accounting for approximately 5% of all uterine cancers. They classified
into pure sarcomas, mixed epithelial sarcomas and heterologous sarcomas. The most common
types are leiomyosarcomas and carcinosarcomas.
Pure sarcomas
This group includes:
❖ Endometrial stromal sarcomas. Endometrial stromal sarcomas occur in perimenopausal
women presenting with irregular bleeding and a soft, enlarged uterus. The majority are
low grade and surgery is the main treatment.
❖ Leiomyosarcomas are rare tumours of the myometrium. Rarely (0.75%), they are
associated with malignant transformation of benign fibroids and present with a rapidly
growing pelvic mass and pain. Preoperative diagnosis is difficult, but may be aided by
MRI. The uterus is enlarged and soft on palpation. Surgery is the main treatment and
adjuvant treatment considered if the mitotic count is high (above 10 mitoses per high-
powered field). Metastatic spread is usually vascular to distant sites, such as lung and
brain.
Mixed epithelial sarcomas (carcinosarcomas)
This group of tumours, formerly known as malignant mixed Müllerian tumours, contain both
carcinomatous and sarcomatous elements. The carcinomatous component is usually glandular
and the sarcomatous component is homologous (endometrial, stromal and/or smooth muscle)
or heterologous (tissues not normally found in the uterus, including bone, cartilage and
skeletal muscle).
The majority present after the menopause and sometimes there is a history of previous pelvic
irradiation. There is usually a history of PMB and a fleshy mass is often seen protruding from
the cervix along with an enlarged soft uterus. Treatment is surgery followed by postoperative
radiotherapy. The 5-year survival is 73% if confined to the uterus, but only 25% if the tumour
has spread outside the uterus.
Heterologous sarcomas
This rare group of tumours consists of sarcomatous tissue not usually found in the uterus, such
as striated muscle, bone or cartilage. The most common is rhabdomyosarcoma, which may
present in children as a grape-like mass protruding from the cervix with a watery discharge.
Histology reveals primitive rhabdomyoblasts. Recurrence rates are high with distant
metastases.

Dr. Rasha Shakir AL-Samaraee