Endometrial carcinoma (endometrial carcinorna) is a group of epithelial malignant tumors occurring in the endometrium, with adenocarcinoma derived from endometrial glands being the most common. It is one of the three major malignant tumors of the female genital tract, accounting for 7% of all malignant tumors in women and 20%-30% of malignant tumors of the female genital tract. In recent years, the incidence of adenocarcinoma has been increasing worldwide.
1.Etiology and pathogenesis
The etiology is not very clear. At present, it is believed that there may be two types of endometrial cancer. One type is estrogen-dependent, which may occur under the long-term effect of estrogen without progestin antagonism, and endometrial hyperplasia (simple or complex, with or without atypical hyperplasia), or even cancer. It is commonly seen clinically in anovulatory disorders (anovulatory uterine bleeding, polycystic ovary syndrome), estrogen-secreting ovarian tumors (granulosa cell tumors, follicular membrane cell tumors), postmenopausal women who have been taking estrogen for a long time, and women who have been taking tamoxifen for a long time.
This type accounts for the majority of endometrial cancers, all of which are endometrioid adenocarcinomas with better tumor differentiation, high estrogen and progesterone receptor positivity, and good prognosis. Patients are younger and are often associated with obesity, hypertension, diabetes, infertility or sterility and delayed menopause. About 20% of patients with endometrial cancer have a family history. The other type is estrogen-independent, in which there is no clear relationship between the development of endometrial cancer and estrogen.
These are rare types of endometrial cancer, such as endometrial plasma papillary carcinoma, clear cell carcinoma, adenosquamous carcinoma, and mucinous carcinoma. The tumor is highly malignant, poorly differentiated, negative for estrogen and progesterone receptors, and has poor prognosis. Qiu Zhiyuan, Department of Medical Oncology (Chemotherapy), Zhenjiang First People’s Hospital
2.Pathology
(1) Visual examination
There is no obvious difference in the visual presentation of different histological types of endothelial carcinoma. It can be broadly divided into diffuse type and focal type.
Diffuse type: Most or all of endometrium is invaded by cancerous tissues and protrudes into the official cavity, often accompanied by hemorrhage and necrosis, and rarely infiltrated by muscular layer. In advanced stage, the cancer foci may invade deep myometrium or cervix, which may cause pus accumulation in the uterine cavity if the cervical canal is obstructed.
Focal type: Mostly found in the bottom of the official cavity or the horn of the uterus, the cancer foci are small, in the shape of polyps or cauliflower, and easily infiltrate the myometrium.
(2) Microscopic examination and pathological types
Endometrioid adenocarcinoma: 80% to 90% of the cases are endometrial glands with highly abnormal hyperplasia, epithelial complexes and sieve-like structures. The cancer cells are obviously heterogeneous, with large, irregular and deep-stained nuclei, active nuclear division, few poorly differentiated adenocarcinoma glands, loss of glandular structure, and solid cancer mass. Adenocarcinoma is classified into grade I (highly differentiated, G1), grade II (moderately differentiated, G2) and grade III (poorly differentiated, G3) according to the degree of differentiation. The higher the grade, the higher the malignancy.
Adenocarcinoma with squamous epithelial differentiation: Adenocarcinoma with squamous epithelial component is called sphenoid adenocarcinoma (adenokeratosis), and with squamous carcinoma is called squamous adenocarcinoma, and in between is called adenocarcinoma with squamous epithelial atypical hyperplasia.
Plasmacytoid adenocarcinoma: It is also called papillary plasmacytoid adenocarcinoma (UPSC), accounting for 1% to 9%. The cancer cells are heterogeneous, mostly irregularly arranged in complex layers, with papillary or clustered growth, and 1/3 may be accompanied by sand granules. It is highly malignant and prone to deep muscle layer infiltration and abdominal, lymphatic and distant metastasis, with very poor prognosis. Abdominal dissemination may also occur when there is no obvious muscle layer infiltration.
Clear cell carcinoma: Most of them are solid lamellar, adeno-tubular or papillary in shape, with abundant and translucent cytoplasm and heterogeneous nuclei, or composed of nail-like cells. It is highly malignant and easy to metastasize at an early stage.
3.Clinical manifestations
Symptoms: No obvious symptoms in the early stage, but vaginal bleeding, vaginal discharge, pain, etc. appear later.
Vaginal bleeding: It is mainly manifested as vaginal bleeding after menopause, and the amount is usually not much. Those who have not yet menopause may show increased menstruation, prolonged menstruation or menstrual disorder.
Vaginal discharge: mostly bloody fluid or plasma discharge, or pus and blood discharge if combined with infection. About 25% of patients visit the doctor for abnormal vaginal discharge.
Lower abdominal pain and others: If the cancer involves the inner cervical opening, it may cause pus accumulation in the official cavity and lower abdominal distension and cramp-like pain. Late infiltration of surrounding tissues or compression of nerves may cause pain in lower abdomen and lumbosacral region. In the late stage, corresponding symptoms such as anemia, emaciation and cachexia may appear.
Signs: Early stage patients may have no abnormal findings in gynecological examination. In late stage, the uterus may be obviously enlarged, and there may be obvious tenderness when combined with pus accumulation in the official cavity, and cancerous tissues may occasionally come out from the cervical canal and bleed easily when touched. When the cancer infiltrates the surrounding tissues, the uterus may be fixed or irregular nodules may be found in the parametrium.
4.Treatment
The main treatment methods are surgery, radiotherapy and drug (chemical and hormone) treatment. The appropriate treatment plan should be selected and formulated according to the patient’s general condition, the extent of cancer involvement and histological type. In early stage, surgery is the main treatment, and adjuvant treatment is chosen according to the results of surgery-pathological staging and the presence of high-risk factors for recurrence; in late stage, a combination of surgery, radiation and drugs is used.
Surgical treatment: The purpose of surgery is to perform surgical-pathological staging to determine the extent of lesions and factors related to prognosis, and to remove the cancerous uterus and other possible metastatic lesions, which is the main treatment method for endometrial cancer. The surgical procedures are: a straight incision in the middle of the abdomen, opening the abdominal cavity and immediately taking pelvic and abdominal irrigation fluid, and then carefully exploring the whole abdominal organs. The greater omentum, liver, peritoneum, rectal uterine sink, and adnexal surfaces are examined.
Any possible metastatic lesions are palpated, and suspicious or enlarged lymph nodes in the para-aortic and pelvic cavities are carefully palpated. The uterus and both adnexa are removed, and the resected uterine specimen is dissected to determine the presence or absence of muscle infiltration. In those with high-risk factors, the retroperitoneal lymph nodes are removed. The surgically resected specimen should be routinely examined pathologically, and the cancer tissue should also be tested for estrogen and progesterone receptors as a basis for selecting adjuvant therapy after surgery.
Stage I patients should undergo extra-fascial total hysterectomy and bilateral adnexal resection.
Pelvic and para-aortic lymph node resection or sampling should be performed if one of the following conditions exists.
(i) Suspected para-aortic and common iliac lymph nodes and enlarged pelvic lymph nodes;
②Special pathological types, such as papillary plasmacytoma, clear cell carcinoma, squamous cell carcinoma, carcinosarcoma, undifferentiated carcinoma, etc;
③Endometrioid adenocarcinoma G3;
(iv) Myometrial infiltration depth ≥1/2;
⑤ The area of the uterine cavity involved in the cancer is more than 50%.
In stage II, modified radical hysterectomy and bilateral adnexal resection should be performed, along with pelvic and para-aortic lymph node dissection. In stages III and IV, the scope of surgery is the same as that of ovarian cancer, and tumor cytoreductive surgery is performed.
Radiotherapy: It is one of the effective methods for treating endometrial cancer and is divided into two types: intracavitary irradiation and extracorporeal irradiation. Intracavitary irradiation is mostly done with a post-mounted treatment machine, and the high-energy radiation source is 60 cobalt or 137 cesium. Extracorporeal irradiation is commonly used with 60 cobalt or linear gas pedal.
Radiation therapy alone: only used for advanced patients who have contraindications to surgery or cannot be surgically removed. The total dose of intracavitary irradiation is 45~50 Gy. The total dose of extracorporeal irradiation is 40~45 Gy. For stage I G1 and those who cannot receive surgical treatment, simple intracavitary irradiation can be used, but all other stages should be treated with combined intracavitary and extracorporeal irradiation.
Postoperative radiotherapy: It is the main postoperative adjuvant treatment for endometrial cancer, which can significantly reduce local recurrence and improve survival rate. For patients with deep muscle infiltration, lymph node metastasis, pelvic and vaginal residual lesions, radiotherapy should be added after surgery.
Chemotherapy: It is one of the comprehensive treatment measures for advanced or recurrent endometrial cancer. It is also used for the treatment of postoperative patients with high risk factors for recurrence in order to reduce distant metastases outside the pelvis. Commonly used chemotherapeutic drugs include cisplatin, adriamycin, paclitaxel, cyclophosphamide, fluorouracil, mitomycin, etoposide, etc. They can be applied alone or in combination, or can be combined with progestins. Postoperative chemotherapy should be given for papillary plasmacytoma of the uterus, and the regimen is the same as that for epithelial carcinoma of the ovary.
Progestin therapy: Progestin can be used for advanced or recurrent cancer, also for the treatment of atypical endometrial hyperplasia and for patients who require preservation of reproductive function in very early stages. The mechanism may be that progestins act on cancer cells and bind to progestin receptors to form a complex that enters the nucleus, delaying DNA and RNA replication and inhibiting cancer cell growth. Progestin should be applied in high doses for a long period of time with high efficiency, and the efficacy should be evaluated after at least 12 weeks of application. Progesterone receptor (PR) positive patients can have an efficiency of 80%. Commonly used drugs: 200~400mg/d of oral medroxyprogesterone acetate; 500mg of progesterone caproate, injected intramuscularly twice a week. Long-term use may have side effects such as sodium retention, swelling or drug-related hepatitis, which can be recovered after stopping the drug.
5.Prognosis
The main factors affecting prognosis are
Biological malignancy degree and lesion scope of the cancer, including pathological type, histological grading, depth of muscle layer infiltration, lymphatic metastasis and extra-uterine lesions, etc;
Patient’s general condition;
Treatment plan selection.
After treatment, regular follow-up should be performed. 75%-95% of recurrences occur within 2-3 years after surgery. The follow-up should include detailed medical history, pelvic examination, vaginal cytology smear, chest X-ray, serum CA125 test, and CT and MRI examination if necessary. Generally, follow-up visits should be made every 3 months for 2~3 years after surgery, every 6 months after 3 years, and once a year after 5 years.
6.Prevention
Preventive measures include.
(1) Popularize the knowledge of cancer prevention and regular medical checkups;
(2) Pay attention to the diagnosis and treatment of vaginal bleeding in postmenopausal women and menstrual disorders in women in menopausal transition;
(3) Properly grasp the indications and methods of estrogen application;
(4) Close follow-up or monitoring should be performed for those with high-risk factors.