- Clinical science
Endometrial cancer is the most common cancer of the female genital tract in the US, with a peak incidence between 60 and 70 years of age. Endometrial cancers can be divided into two types based on histological characteristic; type I cancers account for 75% of all endometrial cancers and are of endometrioid origin, while type II cancers originate from serous or clear cells. Several risk factors are associated with the development of endometrial cancer, of which the most important is long-term exposure to increased estrogen levels, especially in type I cancer. The main symptom is often painless, vaginal bleeding, which presents at an early stage. Later stages may manifest with pelvic pain and a palpable mass, whereby pelvic exams are often normal. The diagnosis is made primarily via an endometrial biopsy, which shows endometrial hyperplasia and atypical cells. Additional imaging studies (e.g., ultrasonography, abdominal CT, X-ray) are usually required for the detection and staging of metastases. Treatment of early stage endometrial cancer involves hysterectomy with adnexectomy and may also require additional lymph node removal. Radical hysterectomy according to the Wertheim-Meigs method is performed in cases of advanced carcinomas and can be combined with radiotherapy and progestin treatment. The prognosis is usually favorable in cancers diagnosed at an early stage.
The development of type I endometrial cancers has been shown to be directly related to long-term exposure to increased estrogen levels. Type II endometrial cancer is mostly estrogen-independent and is strongly associated with a genetic predisposition.
Risk factors for estrogen-dependent tumors
- Early menarche; and late menopause
- (polycystic ovary syndrome)
- Unopposed estrogen replacement therapy (e.g., for menopausal symptoms)
- Breast cancer: history of breast cancer, tamoxifen treatment
- (esp. obesity and diabetes mellitus type 2 )
- (hereditary nonpolyposis colorectal cancer)
- Combination oral contraceptive pills
- Tobacco consumption
- Regular physical exercise
- Lifelong soy-rich diet
- The most common cancer of the female genital tract in the US
- Fourth most common cancer in women (after breast, lung, and colorectal cancer)
- Age: primarily postmenopausal women affected; peak incidence at 65–74 years
Epidemiological data refers to the US, unless otherwise specified.
- Abnormal uterine bleeding is the main symptom.
- Later stages may present with pelvic pain, palpable abdominal mass, and/or weight loss.
- Pelvic exam is often normal; possible findings include an abnormal cervix, enlarged uterus, or evidence of local metastases (see below).
The majority of endometrial cancers are diagnosed at an early stage and have a good prognosis!
- Localized metastasis: contiguous spread to the cervix and vagina, fallopian tubes, and ovaries (25% of cases)
- Lymphogenic metastasis: seen in late stage cases; retroperitoneal spread, or involvement of the pelvic and/or para-aortic lymph nodes
- Hematogenic metastasis: rare; occurs at a very late stage and usually in the lungs
- Etiology: increased estrogen stimulation leads to excessive proliferation of the endometrium, e.g., in:
Classification: based on histology
- Simple endometrial hyperplasia
Complex endometrial hyperplasia
Histology: pronounced proliferation of glandular tissue. The glands are positioned, in part, back-to-back ("dos-à-dos") with no separating stroma
- Grades I–II: no nuclear atypia
- Grade III: additional cell atypia such as extensive mitosis and loss of cell polarity
- Risk of carcinoma
- Histology: pronounced proliferation of glandular tissue. The glands are positioned, in part, back-to-back ("dos-à-dos") with no separating stroma
- Clinical features: constant bleeding, intermenstrual bleeding, postmenopausal bleeding
- Treatment: : the choice of treatment primarily depends on the presence of atypia and the age of the patient
|Premenopausal women||Postmenopausal women|
|Endometrial hyperplasia without atypia|| || |
|Endometrial hyperplasia with atypia|| || |
Endometrial biopsy with histology
- Procedures: most commonly performed as part of a pelvic exam; alternatives include hysteroscopy-guided biopsy or dilatation and curettage
- Results: endometrial hyperplasia, with or without atypia is seen; pronounced proliferation of glandular tissue (characteristic of endometrial adenocarcinoma)
- If there is no detectable pathology on biopsy and if no further symptoms occur, endometrial cancer can be ruled out.
- Transvaginal ultrasonography
- Abdominal ultrasonography: A complete abdominal ultrasound is indicated to exclude metastasis.
- Chest x-ray, CT, MRI: assessment of metastatic spread (lungs, pelvis)
- Laboratory tests: CBC and coagulation studies to assess anemia and possible other causes of heavy uterine bleeding
- Indication: women with endometrial cancer who are postmenopausal, perimenopausal, or do not intend to become pregnant
- Medical management