MALIGNANT DISEASE OF THE UTERUS

Lectures on Gynecology Dr Magda Helmi

Endometrioid adenocarcinoma:type 1 cancers account for 90 per cent of endometrial adenocarcinomas, are oestrogen dependent, occur in younger women and have a good prognosis. Serous papillary carcinoma: type 2 cancers occur in elderly women, are non-oestrogen dependent and have much poorer prognosis. Clear cell carcinoma can rarely arise from the endometrium.

Uterine papillary serous carcinomaEndometrioid endometrial adenocarcinoma

EpidemiologyWorldwide, approximately 320,000 women

are diagnosed with endometrial cancer

each year, making it the fifth most

prevalent cancer in women. It is more

common in developed countries; the risk of

endometrial cancer is 1.6% compared to

0.6% in developing countries. Unlike most

cancers, the incidence rate has risen

dramatically in recent years, including an

increase of over 40% in the United

Kingdom between 1993 and 2013.

Risk factors for endometrial cancerObesityDiabetesNulliparousLate menopause >52 yearsUnopposed oestrogen therapyTamoxifen therapyHormone replacement therapy Y NFamily history of colorectal or ovarian cancer

Signs and symptomsVaginal bleeding and/or spotting in postmenopausal women are a common early sign of endometrial cancer, especially in its adenocarcinoma form; it is seen in approximately 2/3 of cases.Abnormal menstrual periods or extremely long,

heavy, or frequent episodes of bleeding in premenopausal women may also signify endometrial cancer. Thin white or clear vaginal discharge is a symptom in postmenopausal women. More advanced disease shows more obvious

symptoms or signs.

physical examination :Pelvic examinations are frequently normal , The uterus may become enlarged or the cancer may spread, causing lower abdominal pain or pelvic cramping.Pyometra may occur in advanced cases of the

disease.These symptoms, not including bleeding, are often not indicative of endometrial cancer; it is the cause of these symptoms in 10-15% of women.

Diagnosis

Transvaginal ultrasound

CT scans

MRI is also useful for examining the nearby lymph nodes.

Dilation and curettage or an endometrial biopsy

DiagnosisThere is a continuing debate about the value of hysteroscopy in diagnosis of serious endometrial diseases, such as cancer, hyperplasia, or both. This is because individual studies on histopathologic validation of endoscopic visual interpretation are small, leading to imprecise and heterogeneous estimates of accuracy.

Endometrial carcinoma is surgically staged using the FIGO cancer staging system. • IA: Tumor is confined to the uterus with less than half myometrial invasion• IB: Tumor is confined to the uterus with more than half 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 invades bladder mucosa and/or bowel mucosa• IVB: Distant metastases including abdominal metastases and/or inguinal lymph nodesMyometrial invasion and involvement of the pelvic and para-aortic lymph nodes are the most commonly seen patterns of spread.

Histopathological ClassificationThe two subtypes are genetically distinct.

Type I endometrial carcinomas occur most commonly in pre- menopausal women, are more common in white women, often with a history of endometrial hyperplasia. Type I endometrial cancers are often low-grade, minimally invasive into the underlying uterine wall (myometrium), estrogen-dependent, and carry a good prognosis. Type I carcinomas represent 75%-90% of endometrial cancer.

Type II endometrial carcinomas usually occur in older, post-menopausal women, are more common in Black women, and are not associated with increased exposure to estrogen or a history of endometrial hyperplasia. Type II endometrial cancers are often high-grade, with deep invasion into the underlying uterine wall (myometrium), and are of the serous or clear cell type, and carry a poorer prognosis.

Type IType II

Metastasisovaries and Fallopian

uterus, and the cervix

When the lymphatic system is involved, the pelvic and para-aortal nodes are usually first to become involved

SurgeryAs the majority of patients present with stage 1 disease, surgery is the most common treatment for endometrial cancer. The extent of surgery will depend on a number of factors including; grade of disease, MRI stage and the patient’s co morbidities.

Adjuvant treatments Postoperative radiotherapy will reduce the local recurrence rate but does not influence survival.local radiotherapy to the vaginal vault given over a short period of time (high-dose radiotherapy, HDR), external beam radiotherapy given for locally advanced disease (stage 3) in combination with HDR. Chemotherapy may also be given for metastatic disease to combat the risk of distant spread of the cancer..

Treatment of recurrencesChemotherapy is often used to treat recurrent endometrial cancer, particularly capecitabine and gemcitabine.

Stage 5 year survival rate

I-A 88%

I-B 75%

II 69%

III-A 58%

III-B 50%

III-C 47%

IV-A 17%

IV-B 15%

Survival rates5-year relative survival rates by FIGO stage:

Recurrence ratesRecurrence of early stage endometrial cancer ranges from 3 to 17%, depending on primary and adjuvant treatment. Most recurrences (70%) occur in the first three years.Higher-staged cancers are more

likely to recur

AdenosarcomaEpidemiologyThese are rare tumours accounting for approximately 5 per cent of all uterine cancers. They are classified into pure sarcomas, heterogonous sarcomas or mixed epithelial sarcomas depending on tissue type present in the histological specimen.

ClassificationPure sarcomas

This group includes endometrial stromal sarcomas (ESS) and leiomyosarcoma. ESS typically occur in perimenopausal women between 45 and 50 years,

Mixed epithelial sarcomas (carcinosarcoma)

This group of tumours, formerly known as mixed mesenchymal tumours contains both carcinoma and sarcoma.

Heterologous sarcomas

This rare group of tumours consists of sarcomatous tissue not usually found in the uterus, such as striated muscle, bone or cartilage.

Pure sarcomas

carcinosarcoma

Heterologous sarcomas

EtiologyAdenosarcomas have been reported in women treated with tamoxifen and after prior pelvic radiation. No association of adenosarcoma with obesity or hypertension has been reported.No known racial or other epidemiologic features associated with endometrial carcinoma have been linked to adenosarcomas.

Location

Approximately 90% of adenosarcomas arise in the uterine corpus, but cervical, vaginal, tubal, ovarian, and primary peritoneal adenosarcomas have also been reported.

Clinical FeaturesThe most common clinical

feature of adenosarcoma

is abnormal vaginal

bleeding, many times

associated with an

enlarged uterus, pelvic

pain,

and tissue protruding from

the cervical os

Prognosis and Predictive FactorsMost patients are considered cured of adenosarcoma after simple hysterectomy; however, they require long-term follow-up, as recurrences generally occur more than 5 years later. Recurrences tend to occur in the pelvis, with distant metastases (eg, to the lung) following local recurrence.