I. What is uterine smooth muscle sarcoma? Uterine fibroid is the most common benign tumor of female reproductive system, on the contrary, uterine sarcoma is a very rare but malignant tumor with high malignancy and poor prognosis, accounting for about 1% to 3% of gynecological malignant tumors and 3% to 7% of uterine malignant tumors, although it is only a word difference. Uterine smooth muscle sarcoma originates from uterine smooth muscle and is the most common type of uterine sarcoma, accounting for about 40% of the tissues. This is followed by endometrial mesenchymal sarcoma, which accounts for about 10% to 15%. This article focuses on the clinical features, pathologic characteristics, and prognostic and therapeutic aspects related to uterine smooth muscle sarcoma. Can uterine smooth muscle sarcoma become malignant to uterine smooth muscle sarcoma? Many patients with uterine fibroids worry about the malignant transformation of fibroids into uterine sarcoma, in fact, only very few smooth muscle sarcomas are malignant from uterine smooth muscle tumors, and the cause of uterine smooth muscle sarcoma is still unknown. What are the signs and symptoms of uterine smooth muscle sarcoma? The majority of uterine smooth muscle sarcomas occur after the age of 40, especially in postmenopausal women, and a few occur in younger women. In a study of 1,396 patients with uterine smooth muscle sarcoma in the United States, the average age of the patients was 52 years, and the main symptoms were lower abdominal pain (53%), lower abdominal distension or vague pain. Irregular vaginal bleeding ( 35%), especially after menopause. Pelvic masses ( 14%), especially postmenopausal abdominal masses, are rapidly growing. Tumor rupture, intra-abdominal bleeding leading to acute abdominal pain and shock may occur. If there is extra-uterine metastasis and distant metastasis, the corresponding clinical manifestations will appear, such as coughing and hemoptysis in pulmonary metastasis; cachexia and other cachectic symptoms such as poor appetite, emaciation and anemia in advanced stage patients. The most common sign is rapid enlargement of the uterine mass, especially after menopause. The above symptoms and signs are similar to those of common uterine smooth muscle tumors and adenomyosis. There is no obvious specificity and it is very difficult to distinguish smooth muscle sarcoma from smooth muscle tumor preoperatively by clinical signs and symptoms alone. Only patients with abnormal vaginal bleeding and/or postmenopausal vaginal bleeding with lower abdominal pain or abdominal mass and an enlarged uterus should be alerted. Patients who have been treated with uterine artery embolization for a smooth muscle tumor diagnosed on imaging and who have a “myoma” that shrinks and then grows more rapidly should also be alerted. What auxiliary tests can be done to confirm the diagnosis of uterine smooth muscle sarcoma in the above cases? PET-CT can absorb 18-fluorodeoxyglucose (18F-FDG), therefore, it can diagnose uterine sarcoma better morphologically and anatomically and is the most valuable test. Umesaki et al. reported that five patients with uterine sarcoma had a diagnostic compliance rate of 100%, 80%, and 40% by PET-CT, MRI, and Doppler ultrasonography, respectively. However, due to the low incidence of uterine sarcoma, the high cost of PET-CT, and the low detection rate of low-grade, small lesions and metastases, PET-CT is currently used less for preoperative screening and diagnosis and more for the evaluation of metastases and recurrence of uterine sarcoma. In conclusion, preoperative diagnosis of uterine smooth muscle sarcoma, whether based on clinical symptoms and signs or imaging examinations and tumor markers, is difficult at an early stage and prone to misdiagnosis resulting in delayed treatment. It is not possible to infer uterine smooth muscle sarcoma by experience. The final diagnosis must be made by surgical pathology. V. Can the diagnosis of uterine smooth muscle sarcoma be confirmed during surgery? For patients who have the above clinical manifestations but cannot be diagnosed before surgery for hysterectomy or myomectomy, intraoperative dissection of uterus and tumor and sending frozen pathological examination can initially determine the benign and malignant and guide clinical treatment, but due to the complex tissue type of uterine sarcoma, there is some error between frozen pathological examination and final pathological results. Secondary surgery is sometimes difficult to avoid. The pathological diagnostic criteria of uterine smooth muscle sarcoma include three indicators: microscopic cells with obvious heterogeneity, nuclear division index >10/10HPF, and coagulative necrosis of tumor cells. Because of the many types of uterine sarcomas and their complex histology, pathologic diagnosis is often difficult in practice. For example, smooth muscle sarcoma of the uterus should be distinguished from certain specific types of uterine sarcoma, and especially from smooth muscle tumors of variable malignant potential. The three indicators for the diagnosis of uterine smooth muscle sarcoma are also seen in “smooth muscle tumors of indeterminate malignant potential”, but none of them meet the criteria. The pathological diagnosis is the final diagnosis, which is related to treatment and prognosis, and it is crucial to be accurate. In addition, since pathological diagnosis is a morphological diagnosis, the ability and level of the pathologist to read the films has a direct relationship with the accuracy of the diagnosis. How to treat uterine smooth muscle sarcoma? The clinicopathological features and biological behavior of various tissue types of uterine sarcoma are different, so it is difficult to determine the appropriate treatment for uterine sarcoma. Surgery is the main treatment method, but a significant percentage of patients are diagnosed with uterine sarcoma and undergo “fibroid” resection before surgery, and are diagnosed with uterine sarcoma only after intraoperative frozen pathology or postoperative pathology. For pathologically diagnosed uterine smooth muscle sarcoma, total hysterectomy and bilateral adnexal resection via extra-abdominal fascia is usually sufficient, and if there is an extra-uterine lesion, it should be removed. There are two controversies regarding the extent of surgery for uterine smooth muscle sarcoma: 1) whether to preserve the ovaries in young patients in the early stages. A recent large study of 1396 cases in the United States concluded that ovarian metastases from uterine smooth muscle sarcoma are rare and that preservation of the ovaries does not affect patient survival, and that preservation of the ovaries can be considered in young, early-stage patients unless metastases to the ovaries are visible to the naked eye. Bilateral adnexal resection has no significant effect on the progression of the lesion, but after all, there is still about 3-4% ovarian metastasis rate, and patients should make a well-informed decision whether to preserve the ovaries. 2. Whether pelvic lymph nodes and para-aortic lymph nodes are routinely removed. The lymph node metastasis rate of uterine smooth muscle sarcoma is about 3% to 9.1%, which mostly occurs in advanced stages. In view of this, lymph node dissection is not recommended routinely unless preoperative CT or MRI examination shows enlarged lymph nodes, intraoperative exploration reveals abnormally enlarged lymph nodes, or extra-uterine metastatic lesions are present. The potential risks of laparoscopic resection of uterine fibroids With the prevalence of laparoscopic surgery, more and more patients are requesting laparoscopic resection of fibroids to preserve the uterus, even in perimenopausal women. After intraoperative removal of the fibroids, they need to be crushed with a rotary cutter and removed from the body before being sent for pathological examination. In the case of uterine smooth muscle sarcoma, there is a risk of abdominal and pelvic implant metastasis during this procedure. Although the incidence of uterine smooth muscle sarcoma is low and the chances of this occurring are low, it must not go unnoticed. Patients requesting the application of laparoscopic removal of sarcoma should give informed consent for this before making a decision. In order to avoid intraoperative dissemination and implantation of uterine sarcoma, it is particularly important to make an accurate preoperative diagnosis and to avoid crushing of the resected myoma. Unfortunately, it is difficult to distinguish the signs and symptoms of uterine smooth muscle sarcoma from uterine fibroids preoperatively, and none of the imaging tests such as tumor markers, ultrasound, CT and MRI can provide a reliable preoperative diagnosis for patients. Therefore, it is not recommended. The only diagnostic value is the rapid growth of fibroids within a short period of time or the rapid growth of fibroids after menopause, which is considered by most scholars to be a rapid growth of fibroids when the size of fibroids increases 1-fold within 3-6 months, but there is controversy. What are the postoperative adjuvant treatments for the diagnosis of uterine smooth muscle sarcoma? There is no definite and effective postoperative adjuvant treatment plan. Radiotherapy may be beneficial in controlling local recurrence but does not improve the overall survival rate. A US study of 1396 patients showed that adjuvant radiotherapy did not improve 5-year survival regardless of stage, while another retrospective study of 920 patients showed that postoperative adjuvant radiotherapy improved 5-year local tumor-free survival but not 5-year survival in patients with stage I lymph node-free metastases. Radiation therapy can be combined with chemotherapy in advanced and recurrent patients. Commonly used chemotherapy regimens are doxorubicin + cisplatin, dacarbazine (azulfiram) + cisplatin (or doxorubicin), which have the potential to improve the prognosis of patients. The recent FIGO recommendation of gemcitabine + docetaxel can have an improvement rate of 27% to 36% for advanced or recurrent tumors. There is also no ideal combination chemotherapy regimen. X. What is the prognosis of uterine smooth muscle sarcoma? Uterine smooth muscle sarcoma is a very aggressive malignant tumor, prone to distant metastasis and recurrence, even with early diagnosis, the recurrence rate is 53%-71%. 40% of patients have recurrence in the lungs first, followed by the vagina (22%), pelvis (19%), retroperitoneum (12%), bone (9%) and other rare sites. The overall survival rate varies from 15% to 25%, with one study showing an average survival of only 10 months. The prognosis is very poor, and all patients who died within 5 years had smooth muscle sarcoma that had spread outside the pelvis. The key is insensitivity to radiotherapy and chemotherapy, etc. The age of the patient with the tumor, the stage, grading and size of the tumor are factors that affect the prognosis.