The goals of treating any human disease are to prolong life and alleviate symptoms while minimizing treatment-related morbidity and mortality. When a woman presents with a symptomatic uterine mass, this necessarily involves the reasonable exclusion of life-threatening malignancy. Although most patients are eager for expeditious symptom relief, all management options must be weighed in terms of potential risks and likelihood of benefit.

Expectant management is always an option for women with minimally symptomatic uterine fibroids, but there is no data to inform the expectant management of uterine sarcoma. The presence of metastatic disease at the time of diagnosis is an important prognostic indicator for patients with leiomyosarcoma . Although still poor, patients with disease confined to the uterus have the best overall survival [4]; therefore, expectant management of presumed fibroids carries the inherent risk of delaying diagnosis of malignancy. Furthermore, hysterectomy with surgical cytoreduction is the only intervention that has ever been proven to improve survival in uterine leiomyosarcoma [44]. Although previously advocated by some experts, serial imaging to exclude a rapidly enlarging uterine mass is not helpful since the incidence of sarcoma in these patients is actually not increased [45]. The absolute risk of delayed diagnosis is unclear since there is no data on the risk of progression based on tumor characteristics such as lesion size or growth rate.

Over the last two decades, conservative management of symptomatic fibroids with selective uterine artery embolization (UAE) has become increasingly popular, and there are several published case reports of women who have been subsequently diagnosed with leiomyosarcoma after undergoing UAE for presumed leiomyomas [46–48]. The true incidence of uterine sarcoma in women undergoing UAE is impossible to determine, but it is reasonable to assume that it is similar to women undergoing myomectomy or hysterectomy for presumed fibroids. It is unclear how embolization of an occult sarcoma affects the tumor’s potential for growth and dissemination, but UAE certainly delays diagnosis. One review of the available case reports suggested a mean diagnostic delay of 8 months (range 1 day to 15 months) and noted that younger patients were more likely to experience longer delays [46]. All of the women in that review presented with continued abnormal uterine bleeding in the months following their procedures; therefore, it is reasonable to consider early failure of UAE an indication for further evaluation as it may be suggestive of occult malignancy.

Similarly, there are multiple case reports of leiomyosarcomas inadvertently treated with leuprolide acetate [49–51]. Over 40% of leiomyosarcomas express estrogen and progesterone receptors [52]; therefore they may initially respond to the hypoestrogenic effects of gonadotropin-releasing hormone analogues in a fashion similar to leiomyomas. One case report identified similar microscopic degenerative and vascular changes such as hyalinization, fibrosis, and narrowing of blood vessel lumens as those seen in leuprolide-treated benign leiomyomas [51]. In each of the reported cases, surgical management was eventually indicated due to treatment failure [49–51]. Again, the greatest risk associated with medical management is likely diagnostic delay. Continued or increased vaginal bleeding, worsening pelvic pain, or increasing uterine size while receiving treatment with leuprolide acetate should prompt concern for a possible undiagnosed malignancy.

Myomectomy is often considered the definitive treatment option for women with symptomatic leiomyoma who wish to retain their fertility. The dissemination of uterine tissue, both benign and malignant, has long been recognized as a potential complication of myomectomy. Leiomyomatosis , or the dissemination of benign tissue fragments, has been observed in open and laparoscopic myomectomies both with and without morcellation, and there is no data to describe a difference in incidence between the two modalities [53]. One can reasonably infer that malignant tissue is disseminated in a similar fashion following myomectomy. The impact of tumor morcellation at the time of either myomectomy or hysterectomy has been the subject of much debate in recent years. Unfortunately, the data is difficult to interpret due to the rarity of occult malignancy and the heterogeneous nature of surgical interventions performed in various studies. For example, one of the largest studies available reviewed 56 cases of early stage leiomyosarcoma , 25 of which underwent some form of tumor morcellation and 31 of which had intact specimen removal. Park et al. concluded that tumor morcellation of occult sarcoma increased the rate of abdominopelvic dissemination and negatively affected disease-free (40% vs. 65%) and overall (46% vs. 73%) survival at 5 years [5]. In that analysis, however, no distinctions were made among the variety of surgical procedures, including transvaginal coring with a scalpel and myomectomy with minilaparotomy. Although much interest has focused on the dangers of power morcellation, it is likely that only one case of power morcellation was included in Park’s 2011 study [53]. Similarly, Perri et al. reported a significantly higher recurrence rate and lower overall survival in women treated with anything other than total hysterectomy. The hazard ratios for recurrence and survival for total hysterectomy compared to any other surgical intervention, including myomectomy, morcellation, and supracervical hysterectomy, were 0.39 and 0.36, respectively [54]. From this limited data, it is possible that any tumor disruption, including myomectomy without morcellation, can disseminate disease and worsen prognosis in cases of occult leiomyosarcoma. In addition, the accuracy of intraoperative frozen section for leiomyosarcoma is particularly poor with estimates ranging from 11 to 38% [11]. Therefore, myomectomy should be reserved for well-selected patients determined to be at low risk for occult malignancy who have a strong desire to retain fertility. In one review of 41 cases of iatrogenic parasitic myoma, investigators noted that lesions were localized to the dependent portions of the abdomen; therefore, copious irrigation with position changes has been proposed as a theoretical mechanism to reduce tissue dissemination [55]. Given the minimal increase in operative time required for irrigation, this seems to be a reasonable technique if myomectomy is performed, with or without morcellation.

Hysterectomy is the gold standard for both diagnosis and treatment of leiomyosarcoma , and it is the only intervention that has been shown to improve survival. It is reasonable to offer hysterectomy as one of several options to any medically operable woman with symptoms related to presumed leiomyomata, and hysterectomy should be preferred and strongly recommended in women with clinical risk factors or imaging characteristics concerning for malignancy. Although most experts perform bilateral salpingoophorectomy as part of the definitive surgery, there is no data to suggest that this practice decreases mortality. In a review of SEER data including 341 women under 50 years old with early stage leiomyosarcoma, removing the tubes and ovaries had no impact on 5-year disease-specific survival [44]. Despite a lack of supportive data, one reasonable strategy is to consider salpingoophorectomy in women whose tumors are estrogen or progesterone receptor positive. Although beyond the scope of this review, it should be noted that there is no clear benefit to routine lymphadenectomy in patients with leiomyosarcoma limited to the uterus and clinically normal lymph nodes as the risk of occult nodal metastasis is less than 3% [2].

For women diagnosed with an occult leiomyosarcoma after total hysterectomy for presumed fibroids, there does not appear to be any benefit to a secondary surgery, either to remove the ovaries or complete staging. For women who underwent myomectomy or subtotal hysterectomy, however, completion surgery is recommended. Additionally, in women who underwent tumor morcellation , there appears to be a role for reexploration and secondary cytoreduction. In a small study investigating the utility of secondary surgical intervention in women with no evidence of extrauterine spread at the time of initial surgery who underwent morcellation and were subsequently diagnosed with leiomyosarcoma, three of eight women had disseminated intraperitoneal disease at immediate reexploration [56]. Reexploration therefore offers prognostic information and may improve survival if complete cytoreduction can be accomplished [57].

The optimal surgical approach to hysterectomy in women with fibroids is a matter of intense debate. Minimally invasive pelvic surgery offers superior patient outcomes in terms of reduced morbidity and mortality, but often large fibroid uteri cannot be removed through the vagina or laparoscopic port sites without tissue morcellation, which confers the risk of disseminating benign or occult malignant tissue, as described previously. Certainly, in cases that are highly suspicious for uterine sarcoma, the entire uterus should be removed intact. The majority of leiomyosarcomas, however, are not diagnosed preoperatively. Although it appears that patient outcomes are worse when uterine sarcomas are inadvertently morcellated, it should be remembered that current understanding of this phenomenon is extrapolated from two small studies that did not define the method of tumor disruption [54, 58]. Subjecting every woman with a large uterus to conventional laparotomy will result in increased morbidity for patients and overall increases in healthcare costs. Both the American Congress of Obstetricians and Gynecologists and the Society of Gynecologic Oncology continue to support minimally invasive surgery, including the use of power morcellation, in appropriately selected patients undergoing myomectomy or hysterectomy for presumed fibroids [10, 26]. Recently, there has been much interest in contained morcellation as a means of reducing risk related to iatrogenic dissemination of tissue. Contained morcellation refers to the use of a surgical bag or containment system, into which an intact specimen is placed prior to morcellation. Theoretically, morcellation within a bag would decrease tissue dissemination, but there is little data to support improved outcomes in patients undergoing contained morcellation compared to conventional techniques [53]. Contained power morcellation is not well studied and may pose increased risks due to limited visibility of the tissue being morcellated and surrounding organs [10]. One review of 152 patients undergoing total laparoscopic hysterectomy found a statistically significant increase in operative time of 20 min with contained versus non-contained electromechanical morcellation, but the study was underpowered to detect differences in other complications [59]. Recently, a single case report suggested improved outcomes at 2 years of follow-up for a patient who underwent contained morcellation of an occult leiomyosarcoma compared with historical data [60], but no retrospective or prospective trials have specifically investigated patient outcomes or survival.

Although uterine leiomyosarcoma is rare, its incidence among women undergoing surgery for presumed leiomyoma is likely higher than historically thought, and the consequences of delayed diagnosis or surgical mismanagement can be devastating for patients. Clinicians should maintain a high index of suspicion for occult malignancy in women with symptomatic uterine masses. They should be aware of the risk factors associated with uterine sarcomas and understand the utility and limitations of available imaging modalities. It would be cost-prohibitive to perform an exhaustive preoperative evaluation for every patient with suspected fibroids, but gynecologists should be cognizant of the tools available to them. For a patient deemed to be high risk for occult malignancy based on clinical risk factors, a history of failed medical management or UAE, or concerning ultrasound findings, further evaluation is indicated. CE-MRI and DWI, possibly with determination of serum LDH, are reasonable investigations. In cases of suspected sarcoma, hysterectomy with intact specimen removal is the preferred management option.