Endometrial cancer is a cancer that arises from the endometrium.

Signs and symptoms

Vaginal bleeding or spotting in women after menopause seen in 90% of cases.

Abnormal menstrual cycles or extremely long, heavy, or frequent episodes of bleeding in women before menopause may also be a sign of endometrial cancer.

Thin white or clear vaginal discharge in postmenopausal women.

Lower abdominal pain or pelvic cramping.

Painful sexual intercourse or painful or difficult urination are less common signs of endometrial cancer.

The uterus may also fill with pus (pyometrea).

Risk factors

• Obesity
• Diabetes mellitus
• Breast cancer
• tamoxiphene
• nulligravida
• late menopause
• unopposed estrogen
• elderly age group
• Lynch syndrome

Protective factors

• Smoking
• use of progestin
• Combined oral contraceptives
• grand multiparity
• Increased physical activity reduces an individual’s risk by 38–46%.

• Pathophysiology
  In 10–20% of endometrial cancers, mostly Grade 3 (the highest grade commonly p53 or PTEN. In 20% of endometrial hyperplasias and 50% of endometrioid cancers.
• PTEN and p27 loss of function mutations are associated with a good prognosis, particularly in obese women.
• The Her2/neu oncogene, which indicates a poor prognosis, is expressed in 20% of endometrioid and serous carcinomas.
• CTNNB1 (beta-catenin; a transcription gene) mutations are found in 14–44% of endometrial cancers and may indicate a good prognosis, but the data is unclear.
• Beta-catenin mutations are commonly found in endometrial cancers with squamous cells.

Diagnosis

Diagnosis of endometrial cancer is made first by a physical examination, endometrial biopsy, or dilation and curettage This tissue is then examined histologically for characteristics of cancer.

If cancer is found, medical imaging may be done to see whether the cancer has spread or invaded tissue.

Classification

Type I endometrial carcinomas occur most commonly before and around the time of menopause. In the United States, they are more common in women

particularly those with a history of endometrial hyperplasia. Type 1 endometrial cancers are often low-grade, minimally invasive into the underlying uterine wall (myometrium), estrogen-dependent, and have a good outcome with treatment. Type I carcinomas represent 75–90% of endometrial cancer.
Type II endometrial carcinomas usually occur in older, post-menopausal people, in the United States 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), are of the serous or clear cell type, and carry a poorer prognosis. They can appear to be epithelial ovarian cancer on evaluation of symptoms. They tend to present later than Type I tumors and are more aggressive, with a greater risk of relapse and/or metastasis.

Endometrioid adenocarcinoma
In endometrioid adenocarcinoma, the cancer cells grow in patterns reminiscent of normal endometrium, with many new glands formed from columnar epithelium with some abnormal nuclei.
Low-grade endometrioid adenocarcinomas have well differentiated cells, have not invaded the myometrium, and are seen alongside endometrial hyperplasia. There are several subtypes of endometrioid adenocarcinoma with similar prognoses, including villoglandular, secretory, and ciliated cell variants. There is also a subtype characterized by squamous differentiation. Some endometrioid adenocarcinomas have foci of mucinous carcinoma.

Serous carcinoma
Serous carcinoma is a Type II endometrial tumor that makes up 5–10% of diagnosed endometrial cancer and is common in postmenopausal women with atrophied endometrium and black women. Serous endometrial carcinoma is aggressive and often invades the myometrium and metastasizes within the peritoneum (seen as omental caking) or the lymphatic system. Histologically, it appears with many atypical nuclei, papillary structures, and, in contrast to endometrioid adenocarcinomas, rounded cells instead of columnar cells. Roughly 30% of endometrial serous carcinomas also have psammoma bodies. Serous carcinomas spread differently than most other endometrial cancers; they can spread outside the uterus without invading the myometrium.
The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene.

Clear cell carcinoma

Clear cell carcinoma is a Type II endometrial tumor that makes up less than 5% of diagnosed endometrial cancer. Like serous cell carcinoma, it is usually

aggressive and carries a poor prognosis. Histologically, it is characterized by the features common to all clear cells: the eponymous clear cytoplasm when H&E stained and visible, distinct cell membranes. The p53 cell signaling system is not active in endometrial clear cell carcinoma. This form of endometrial cancer is more common in postmenopausal women.

Mucinous carcinoma
Mucinous carcinomas are a rare form of endometrial cancer, making up less than 1–2% of all diagnosed endometrial cancer. Mucinous endometrial carcinomas are most often stage I and grade I, giving them a good prognosis. They typically have well-differentiated columnar cells organized into glands with the characteristic mucin in the cytoplasm. Mucinous carcinomas must be differentiated from cervical adenocarcinoma.

Mixed or undifferentiated carcinoma
Mixed carcinomas are those that have both Type I and Type II cells, with one making up at least 10% of the tumor. These include the malignant ,Mullerian tumor which derives from endometrial epithelium and has a poor prognosis.
Undifferentiated endometrial carcinomas make up less than 1–2% of diagnosed endometrial cancers. They have a worse prognosis than grade III tumors. Histologically, these tumors show sheets of identical epithelial cells with no identifiable pattern.

Other carcinomas
Non-metastatic squamous cell carcinoma and transitional cell carcinoma are very rare in the endometrium. Squamous cell carcinoma of the endometrium has a poor prognosis. For primary squamous cell carcinoma of the endometrium (PSCCE) to be diagnosed, there must be no other primary cancer in the endometrium or cervix and it must not be connected to the cervical epithelium. Because of the rarity of this cancer, there are no guidelines for how it should be treated, nor any typical treatment. The common genetic causes remain uncharacterized.

Sarcoma
In contrast to endometrial carcinomas, the uncommon endometrial stromal sarcomas are cancers that originate in the non-glandular connective tissue of the endometrium. They are generally non-aggressive and, if they recur, can take decades. Metastases to the lungs and pelvic or peritoneal cavities are the most frequent. They typically have estrogen and/or progesterone receptors. The prognosis for low-grade endometrial stromal sarcoma is good, with 60–90% five-year survival. High-grade undifferentiated endometrial sarcoma (HGUS) has a worse prognosis, with high rates of recurrence and 25% five-year survival.

Metastasis
Endometrial cancer frequently metastasizes to the ovaries and Fallopian tubeswhen the cancer is located in the upper part of the uterus, and the cervix when the cancer is in the lower part of the uterus. The cancer usually first spreads into the myometrium and the serosa, then into other reproductive and pelvic structures.When the lymphatic system is involved, the pelvic and para-aortic nodes are usually first to become involved, but in no specific pattern, unlike cervical cancer.More distant metastases are spread by the blood and often occur in the lungs, as well as the liver, brain, and bone.Endometrial cancer metastasizes to the lungs 20–25% of the time, more than any other gynecologic cancer.

Histologically classifying

There is a three-tiered system for histologically classifying endometrial cancers, ranging from cancers with well-differentiated cells (grade I), to very poorly-differentiated cells (grade III).
Grade I cancers are the least aggressive and have the best prognosis, while grade III tumors are the most aggressive and likely to recur. Grade II cancers are intermediate between grades I and III in terms of cell differentiation and aggressiveness of disease.

Management

The initial treatment for endometrial cancer is surgery; 90% of women with endometrial cancer are treated with some form of surgery.

Surgical treatment typically consists of hysterectomy including a bilateral salpingo-oophorectomy, which is the removal of the uterus, and both ovaries and Fallopian tubes.

Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is performed for tumors of histologic grade II or above.

In stage III and IV cancers, cytoreductive surgery is the norm, and a biopsy of the omentum may also be included.

In stage IV disease, where there are distant metastases, surgery can be used as part of palliative therapy.

Laparotomy, an open-abdomen procedure, is the traditional surgical procedure; however, in those with presumed early stage primary endometrial cancer, laparoscopy is associated with reduced operative morbidity and similar overall and disease free survival.
Removal of the uterus via the abdomen is recommended over removal of the uterus via the vagina because it gives the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer.