Malignant diseases of the uterus

Malignant diseases of the uterus

Dr.Omar Aldabbas

Assisstant prof.

MUTA university

OBGYN specialist

Endometrial cancer

Endometrial cancer

Epidemiology:

1. Age:

.1Median age (or mean age? Which is more accurate?) is 61 y .

.275-80% 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:.1Nulliparity

2. Anovulation.3PCOS (during their life) (because it comprises hyeprestrogenism and

failure of ovulation)

4. Late Menopause.5Functioning ovarian tumor. Estrogen producing.

Granulose and theca cell tumor.6. Unopposed estrogen therapy

.7Obesity

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. Anti-estrogen 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

Pathology1. Endometrial adenocarcinoma: Is the

commonest about 90%.2. Endometrial adenocarcinoma with

squamous metaplasia (adenoacanthoma)3. Adenosquamous carcinoma4. Papillary serous and clear cell carcinoma

are very rare.90% 10%

Uterus Adenocarcinoma Squamous

Cervix Squamous Adenocarcinoma

Endometrial hyperplasia1. 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. D&C

2. Ovarian ultrasound to exclude Estrogen producing and endometroid tumor.

3. CA 125

4. 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 8-12 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 20-30 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 post-

menopausal, 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

Description Stage

Sarcoma is confined to the corpus I

Sarcoma is confined to the corpus and cervix IISarcoma has spread outside the uterus but is confined

to the true pelvis III

Sarcoma has spread outside the true pelvis IV

TreatmentSurgery: is the only curative therapy for uterine sarcomas Modalities:• Surgery (total abdominal hysterectomy, bilateral salpingo-

oophorectomy). • 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