Malignant diseases
of the uterus
Dr.Omar Aldabbas
Assisstant prof.
MUTA university
OBGYN specialist
Endometrial cancer
Endometrial cancer
Epidemiology:
1. Age:
1.
2.
Median age (or mean age? Which is more accurate?) is 61 y.
75-80% of women are postmenopausal, and 3-5% being less than 40
years old, it peaks in the years before the menopause and plateau
after that.
“Another peak of EC is in the 40s”
2. Country variations: Highest in north America.
3. Racial variations: MORE IN Whites.
Endometrial cancer
• Aetiology: Unknown.
• Unopposed estrogen. So it is more in women
with:
1. Nulliparity
2. Anovulation
(during their life) (because it comprises hyeprestrogenism and
3. PCOS
failure of ovulation)
4. Late Menopause
5. Functioning ovarian tumor. Estrogen producing.
Granulose and theca cell tumor.
6. Unopposed estrogen therapy
7. Obesity
Endometrial cancer
8. Personal or family history of breast or colon cancer, and
family history of endometrial cancer.
9. Tamoxifen therapy (Has estrogenic-type effect on the uterus in particular. Antiestrogen effect on other organs… Only on the uterus it is agonist).
• HRT
While Combined oral contraceptive pills and progesterone
decreases the incidence of endometrial cancer (Only because
they contain progesterone which antagonizes the action of estrogen. Even in the
combined pill, progesterone counteracts the action of estrogen.)
Endometrial cancer
Pathology
1. Endometrial adenocarcinoma: Is the commonest about 90%.
2. Endometrial adenocarcinoma with squamous metaplasia
(adenoacanthoma)
3. Adenosquamous carcinoma
4. Papillary serous and clear cell carcinoma are very rare.
90%
10%
Uterus
Adenocarcinoma
Squamous
Cervix
Squamous
Adenocarcinoma
Endometrial hyperplasia
1. Cystic hyperplasia:
The most common type, rarely seen in association with endometrial
cancer. risk of progression to cancer is 0.4-1.1%. Benign hyperplasia
because the chance of changing into malignant. Not precancerous
lesion.
2. Adenomatous hyperplasia:
Rate of progression to cancer or coexistence with cancer is 0-3.4%
Cystic and adeomatous are benign forms of endometrial hyperplasia
3. Atypical hyperplasia:
Carcinoma may coexist in 25-50% of cases. And progression to cancer
occurs in the rate of 22-33%.
Precancerous lesion. If she completed her family,
Considered as “stage 0” endometrial cancer”
•
•
Or given progesterone for 9 months, take biospy. If the abnormality disappeared, the problem ended and she
can get pregnant.
Endometroid ovarian cancer may co-exist
Endometrial hyperplasia
Presentation of hyperplasia:
• Post-menopausal women will present with abnormal bleeding.
• Before the menopause: irregular or heavy periods
• Perimenopausal bleeding.
Endometrial hyperplasia
Investigations:
1.
2.
3.
4.
D&C
Ovarian ultrasound to exclude Estrogen producing and endometroid tumor.
CA 125
Estradiol estimation.
Endometrial hyperplasia
• Management: depends on the severity of the
condition and her fertility aspirations.
• Cystic and adenomatous hyperplasia: No special
follow up and management depends on further
symptoms of abnormal bleeding.
– Benign forms of hyperplasia
• Atypical hyperplasia: Hysterectomy and bilateral
salpingo-oophorectomy. However, in young women
who want to keep the uterus, give Progesterone for 812 months and repeat D&C.
– It is considered to be “Stage 0 endometrial cancer”.
Endometrial cancer
• Diagnosis and investigations:
• Presenting symptoms:
– Abnormal bleeding. Postmenopausal bleeding in 75-80% of women,.
– A woman who is 60 and gets a single drop of blood, she will doubt it because 10 years
since last menses… So better survival rate because most of the cases are discovered at
early stage. Only one single drop of blood is enough to make the woman worry. If you
examined her.
– Next common cause: Senile vaginits. But even if you saw senile vagina, yo have to do
diagnostic biopsy.
– Pain in late stages.
• Clinical examination: Rarely helpful.
• Look for: enlarged lymph nodes in the groin or supraclavicular area,
metastasis in the posterior vaginal wall, uterus may be enlarged,
Endometrial cancer: Investigations
• Endometrial biopsy can be done as an outpatient
procedure with special cannula (failure rate 20%)
• Ultrasound: vaginal USS to detect tick endometrium in
post-menopausal women, ovarian pathology
• D&C under GA
• Hysteroscopy
Endometrial cancer: Spread of invasive disease:
• Direct: Myometrium,
• Lymphatic: Para-aortic Lymph nodes
– Spread to the cervix may occur by extension, but more commonly
through lymphatic.
• Blood: rarely
•
Mode of spreading depends on the type of tumor:
–
–
Any epithelial tumor spreads by lymphatics and is slower
Sarcoma: Spreads by blood (Very rapid and can kill quickly and will go quickly to the brain, liver, etc. )
Endometrial cancer
Prognostic factors:
1. Stage of the disease
2. Myometrial invasion
3. Degree of differentiation
4. Tumor size
5. Age
FIGO staging of Endometrial cancer
Stage
• IaG123
tumor limited to the endometrium.
• Ib G123
Invasion <0.5 cm myometrium
• Ic G123
Invasion >0.5 cm myometrium
• IIa G123
endocervical glandular involvement only
• IIbG123
Cervical stromal invasion
• IIIaG123:Tumor involves serosa or adnexa (ovaries or tubes) or + ve
peritoneal cytology.
• IIIbG123:Vaginal metastasis
• IIIc G123:Metastasis to pelvic and/or Para-aortic lymph node.
• Iva: tumor invades bladder and or bowel mucosa
• IVb: Distant metastasis including intra-abdominal or inguinal lymph nodes.
•
•
•
G123:referred to the grade of differentiation tumor (1 = well differentiated, 2=moderately, 3 poorly differentiated).
a, b, c: Depends on invasion of the tumor to the myometrium.
If stage II: it reached cervix and is treated as cervical cancer.
Endometrial cancer: Management
• Stage I : TAH+BSO which could be done either
vaginally or abdominally.
• Radiotherapy: vault radiation or external radiation to
the whole pelvis.
• Vaginal radiation to the vault to minimize vault
recurrence.
• Pelvic radiation advised in women with poor
prognostic factors such as invasion more than half
way through the myometrium, high grade and large
tumor
• Adjuvant progesterone therapy: can be used in
advanced and recurrent disease.
• III and IV: no place for surgery. Because you are not aiming at
treating the patient. Radiotherapy only. Some give
progesterone but is hopeless.
• Stage II: Only limited to uterus. Luckily , this is the most
common presentation. Total abdominal hysterectomy, and
bilateral salpingectomy, and maybe omenectomy. If
histopathology, showed it involved > 50% of wall or poorly
differentiated tumor of deposits in cervix or tubes, you need to
give them post-operative radiotherapy. Otherwise, no need for
radiotherapy.
•
•
•
Management: ???
Stage II. Treated as cervical cancer :
Radical Hysterectomy (Whertimes) and pelvic lymph nodes removal + Radiation
Endometrial cancer
Management
Stage III : If there is parametrial extension of the
disease or vaginal involvement, patient should have
CT scan of the pelvis and upper abdomen.
If the tumor is confined to the pelvis, radiation is the
choice. If there is spread to the adnexa, do pelvic
clearance + Omentectomy as for primary ovarian
tumor.
Endometrial cancer
• Stage IV. The lung are most common sites of metastasis
followed by peripheral lymph nodes. Radiation or cytotoxic
drugs and hormonal treatment may be required.
Endometrial cancer
•
•
•
•
•
Hormone replacement therapy:
It safe to use estrogen in women with stage I-II.
If the disease has been removed surgically or by radiation,
then Estrogen has no bad effect on the disease.
Stage II: Cervical tumor is considered as. The cornerstone
stone of treatment. Ia: only cone biospy or simple
hysterectomy.
1b or 2a: Radical or Wertheim hysterectomy. Ovaries,
tubes, parametrial tissue until you reach the ureters. Block
dissection of all of pelvic LNs c(Common iliac, internal
iliac, external iliac, obturator, and presacral LNs)
– Why remove ovaries: EC is estrogen dependent tumor.
– Also, they share the same lymphatics. So there is cross
spread of the two tumors. If endometrial cancer, it might
spread via the lymphatics to the ovaries. Vice versa, an
ovarian cancer can spread via lymphatic to endometrium.
Treatment of ovarian cancer and stage Ia??? Is the same
(hysterectomy, bilateral salpingo-oophorectomy, and maybe
omentectomy.
– Paraaortic drainage
•
2b and above: radiotherapy alone.
Wertheim (veer-time)
operation (Austrian
gynecologist):
a radical operation for
carcinoma of the uterus in
which as much as possible of
the vagina is excised and
there is wide lymph node
excision.
Endometrial cancer
5 years survival rate
Stage 1 =83%, (in some studies, the doctor saw up to 92%)
stage 2= 71%,
stage 3=39%,
stage 4=27%,
all stages= 60%, IN UK, 73%
• When does a patient need post-operative radiation:
– Poor differentiation
– More than 50% of myometrium or more than 0.5 cm
– Microscopic deposits in …
–
What is the aim of radiation? Because more chance of lymphatics involvement in such cases .
Endometrial cancer
• Recurrent disease:70% of all recurrences occurred in the first
2-3 years. Early recurrence carry poor prognosis.
• Can be in any site, but mainly is in the pelvis
Endometrial cancer
• Sites of recurrence: Pelvis, vagina, peritoneal cavity,
lungs, liver, bone, inguinal and supraclavicular lymph
nodes.
• Vault recurrence is more common after surgical
treatment which can be cured.
• Progesterone therapy has a response rate of 15-20%,
G1 will respond better than G2&3
• Cytotoxic drugs has small role following failure of
hormonal therapy.
• Radiation maybe the only therapy. Very poor
prognosis.
Uterine Sarcoma
Challenging
• Rare → Limited data 2% to 5% of all
uterine malignancies
– Prognosis, behavior  Not enough data
– EC: 2-3 cases/ year… US once in 10 years
because is very rare.
• Rapidly growing (doubling time is 4 weeks)
– Rapidly spreading: Kill quickly because is
through BC
• tend to be increasing
Risk Factors
• Prior pelvic radiation (10%-25% of cases)
– Women with cervical cancer, stage Ib or more, this lady might come 2030 years later with US. Generally, all stage of cervical cancer can be
treated by radiation (either surgery alone or surgery + radiation) Surgery
without radiation in stage 1b and IIa (because you can simply do cone
biopsy or simple hysterectomy)
• 3X increase in risk among black women
• An increase in the risk of uterine sarcomas appears to accompany
the use of long-term adjuvant tamoxifen in women with breast
cancer.
– Tamoxifen on uterus: poly, ??/ and cancer
• Should be considered in postmenopausal women with a pelvic
mass, abnormal bleeding, and pelvic pain, where the incidence of
sarcoma is 1 to 2 percent
– Menopause is a treatment for fibroids!
– If post-menopausal, it is very likely to be cancer. If there is a mass with postmenopausal, almost always sarcoma
• Cervical cancer and pregnancy:
- T1 + t2: as if she is not pregnant  Wertheim (pron.: veer-time)
operation “radical” Not total hysterectomy. After radiation, she
will abort.
- Late: wait until end of pregnancy and then Wertheim. After 2
weeks, radiation.
Types
• Mixed mullerian sarcomas - 50%
• Leiomyosarcoma (30%): De-novo, starts
alone. Sarcomatous chance in fibroids is
rare. Mostly, de-novo.
• Endometrial stromal sarcoma (15%)
• Adenosarcoma (5%):
Leiomyosarcoma
• Arise from smooth muscles of the uterus
usually de novo
• appear grossly as a large (>10 cm) yellow
or tan solitary mass with soft, fleshy cut
surfaces exhibiting hemorrhage and
necrosis
Leiomyosarcoma
Yellowish, necrosis, and hemorrhagic area. It reaches
10 cm
Leiomyosarcoma: Low or high grade
• Frequent mitotic figures
• significant nuclear atypia
• presence of coagulative necrosis of tumor
cells
Endometrial stromal tumors :
• A pure homologous neoplasm
– Because there is no other tissue
• Subtypes: low and high grade malignancies
– Based on the number of atypia
• Low grade : slow growing tumors with infrequent
metastasis or recurrence after therapy.
• high grade : enlarge and metastasize quickly
and are often fatal.
Mixed mullerian sarcomas
• Both carcinomatous and sarcomatous elements must be
present in this type of sarcoma.
– CT tumor and epithelial tissue trauma at the same time.
– Behavior of sarcoma wins again behavior of carcinoma (because
it is blood not lymphatics)
• metastasize early in the course of the disease via
hematogenous and lymphatic pathways
• grows as a polypoidal mass with a broad base
Mixed mullerian sarcomas
• Mixed mullerian homologous sarcomas
(carcinosarcoma) contain only tissue
elements that are indigenous to the uterus.
• In contrast, if exogenous tissue not
normally found in the uterus is present (eg,
bone, cartilage), the tumor should be
classified as a mixed heterologous
mullerian sarcoma (mixed mesodermal
sarcoma).
MMT Mixed mesodermal tumor (you
can find bone and calcifications)
Adenosarcoma
• both malignant stromal and benign
epithelial components
• a significantly increased occurrence of this
tumor
• present as polypoid masses in the uterus
• Sarcoma and adenocarcinoma
Clinical Diagnosis
• Vaginal bleeding is the most common
presenting symptom of a uterine sarcoma.
• On pelvic examination, the uterus is
enlarged and, in some patients, part of the
tumor may protrude from the uterine cavity
through the cervical os.
• Rapidly growing!
• Spreads mainly by blood
Evaluation
• Ultrasound examination, MRI, or CT scan
cannot reliably distinguish between a
sarcoma, leiomyoma or endometrial
cancer
• The real diagnosis of uterine sarcomas is
made from histologic examination of the
entire uterus
– Make histology and take the whole sample for
examination
Staging: surgical
based on FIGO staging for endometrial cancer
Stage
Description
I
Sarcoma is confined to the corpus
II
Sarcoma is confined to the corpus and cervix
III
Sarcoma has spread outside the uterus but is confined
to the true pelvis
IV
Sarcoma has spread outside the true pelvis
Treatment
Surgery:
is the only curative therapy for uterine sarcomas
Modalities:
• Surgery (total abdominal hysterectomy, bilateral salpingooophorectomy).
• Surgery plus adjuvant chemotherapy.
• Surgery plus adjuvant irradiation
• Aggressive surgical cytoreduction at the time of initial diagnosis
offers the best survival
• Surgery and chemotherapy is the best combination. Never leave any
part of the tumor: Cytoreduction: remove as much as you can of the
tumor.
Cytoreductive therapy: therapy with the intention of reducing the number of cells in a lesion, usually a
malignancy.
The five year survivals: What
adds to the survival rate?
• Surgery alone (46 %)
• Surgery and radiotherapy (62 %) [improved by
16% so it is something!)
• Surgery and chemotherapy (43 %)
• Radiation alone (8 %)
three-year local recurrence
rates
• No adjuvant treatment 62 %
– If you did not use anything
• Whole pelvis external beam radiation
therapy 31 %
– Radiation: recurrence is worse than primary
tumor
• Chemotherapy alone 71 percent
– Technically, it is not useful. It may be harmful.
Complications of Radiation Tx:
like what you took in the past!!!
Acute:
• Perforation
• Fever
• Diarrhea
• Bladder spasm
Chronic:
• Proctitis
• Cystitis (a/w UTI)
• Fistula (Fistulas
can be caused by
either surgery or
radiation)
• Enteritis
Adjuvant chemotherapy
• The role of chemotherapy in the treatment
of uterine sarcomas has been limited
– Or at least, try new chemotherapeutic agents
Hormone therapy
• Estrogen, progesterone, and other
hormone receptors are present in
leiomyosarcomas and endometrial stromal
sarcomas but do not predict hormone
responsiveness.
• In fact, only one of 28 patients with
residual or recurrent disease following
surgery had an objective response to
hormone therapy
Recurrent Disease
• Most relapses occur in the pelvis, followed
by lung and abdomen
• Currently, no standard therapy for patients
with recurrent disease
• Most will go for radiotherapy because they are not aiming at
curing the patient!!!
Prognosis
Poor prognosis:
• The 5-year survival : stage I less than 50%
• Remaining stages : 0% to 20%.
Poor prognostic factor of leiomyosarcoma:
• Age over 50 years
• Size greater than 5 cm