Endometrial carcinoma

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Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women in the USA after breast cancer, colorectal cancer, and lung cancer, with about 34 000 new cases diagnosed in 1996. It is a disease of peri and postmenopause, and mainly affects postmenopausal women, with incidence peaking between ages 50 and 60. Most cases are associated with prolonged estrogen stimulation, and arise in a background of endometrial hyperplasia.

The most common early form of spread for endometrial carcinoma is direct myometrial invasion, with a staging system roughly divided into < 50% or > 50% myometrial invasion.

Metasteses most commonly occur via pelvic lymph node metastases. Pelvic lymph node dissection is not performed at the time of surgery. Instead, risk of nodal metastases is estimated based on the grade of the tumour and the depth of myometrial invasion. Moderately late, metastases can occur through transtubal migration to the peritoneal cavity, while very late, they can be blood-borne.

Presentation

The most common presenting symptom of patients is vaginal bleeding. Pain is rare, and patients are usually otherwise asymptomatic. In a post-menopausal population, any post-menopausal bleeding in patients on continuous combined HRT or any unexpected post-menopausal bleeding.

In a pre-menopausal population, any intramenstrual bleeding if the patient is > 40 years old should be investigated.

The two most common high risk patient profiles are those patients with PCO-anovulation or unopposed estrogen use.

Primary symptoms are similar to those of other neoplasms, with vaginal bleeding. Bleeding is a very reliable early sign prompting patients to seek attention. Pelvic pain and pressure on the bladder or bowel from uterine enlargement almost never occur. With secondary symptoms, back pain and pelvic pain are rare, but could be caused by pelvic lymph node or para-aortic metastases. Abdominal distention is rare, but could be caused by intrapertoneal metastases.

Because the disease presents with bleeding at such an early stage, patients rarely develop tertiary symptoms such as problems with appetite, weight or energy.

Investigations

Commonly, a pelvic physical examination will be normal, or show a slightly enlarged uterus. The cervix and vagina should look normal.

The investigation of choice for abnormal uterine bleeding in the patient over the age of 40 is an endometrial biopsy with a pipelle and tenaculum, though it may not possible if there is cervical stenosis, or if the patient too uncomfortable.

Two other investigation options are D&C and endometrial ultrasound for endometrial thickness.

Upon pathological gross examination, the uterus is enlarged, and there is a diffuse thickening of the endometrium or a polypoid mass may be present. The surface may be hemorrhagic or necrotic, leading to bleeding, and there may be invasion of the myometrium and cervix. Microscopically, malignant glands replace the endometrium, and atypical endometrial hyperplasia may be adjacent. Grading occurs according to the architecture (how much is glandular and how much is solid) and the degree of nuclear atypia. The lesion may be well differentiated (G1), moderately differentiated (G2), or poorly differentiated (G3). Other histologic variants include adenosquamous carcinoma, serous adenocarcinoma, clear cell carcinoma, and mucinous carcinoma. Of these, poorly differentiated cancers (G3) are likely to recur locally or metastasize, as well as adenosquamous, serous, and clear cell carcinomas.

Prognosis depends mainly on the stage and spread of the cancer, though grade also affects survival. Lymphatic spread is the common mode of metastases.

Management

Endometrial carcinoma can be treated surgically with a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The two most important factors to consider for the pathology report are the depth of myometrial invasion and the grade of the lesion. Depending on the findings, adjuvant radiation and chemotherapy would be used.

Radiation is given to the pelvis only in daily treatments for 20-25 days, combined with several hours of a continuous intravaginal source. Fortunately, this form of radiation treatment is painless. It reduces the risk of pelvic recurrence only, and has no impact on survival. Chemotherapy is rarely used for palliation of systemic (lung, liver, bone or intraabdominal) metastases.

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