Robert L Barbieri, MD
Barbara Goff, MD
Tommaso Falcone, MD, FRCSC, FACOG
Deborah Levine, MD
Rochelle L Garcia, MD
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Benign uterine leiomyomas (fibroids) are the most common pelvic neoplasm in women (estimated lifetime risk of 70 percent in white women and 80 percent in black women) [1-3]. Uterine sarcoma is rare (3 to 7/100,000 in the United States population) and has a poor prognosis . Both present as focal masses in the uterine myometrium. Thus, clinicians who evaluate and manage women with presumed leiomyomas are presented with a clinical challenge: how to assess if one of the many women diagnosed with this common condition actually has a rare type of malignancy while avoiding unnecessary hysterectomy or laparotomy for the vast majority of women with benign uterine masses. While there are differences in the patient populations for the two disorders, there is substantial overlap.
There are several histologic types of uterine sarcoma. The main type of sarcoma that may resemble a leiomyoma is leiomyosarcoma, which typically presents as a myometrial mass. Endometrial stromal sarcoma may present as an endometrial or myometrial mass.
Historically, hysterectomy was the mainstay of treatment for women with a uterine mass. Thus, if uterine sarcoma was present and identified postoperatively on pathologic analysis, there was no missed diagnosis and the treatment received was incomplete but did not worsen prognosis. In current practice, women with presumed benign leiomyomas may be treated with a variety of uterine-sparing alternatives to hysterectomy, including medication, imaging-based interventions (ie, uterine artery embolization or magnetic resonance-guided focused ultrasound), and conservative surgery (myomectomy or endometrial ablation). Nonexcisional therapies for fibroid-related symptoms (eg, medical treatments, endometrial ablation, interventional radiology procedures) do not produce specimens for pathologic examination. Thus, the diagnosis of malignant neoplasm may be missed. In addition, procedures or techniques that disrupt a uterine mass (ie, myomectomy or hysterectomy, especially when the specimen is morcellated) may disseminate neoplasm. Equally important priorities, however, are to avoid unnecessary surgery for the purpose of excluding the rare sarcoma and also to offer the option of minimally invasive approaches in patients at low risk for sarcoma, many of whom have not completed their childbearing.
Approaches to differentiating benign uterine leiomyomas from uterine sarcoma are reviewed here. General principles of the diagnosis of uterine leiomyomas, the diagnosis and treatment of uterine sarcoma, and benign and atypical smooth muscle neoplasm variants are discussed separately. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history" and "Variants of uterine leiomyomas (fibroids)" and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis".)
DIFFERENTIAL DIAGNOSIS OF A UTERINE MASS — The challenge of differentiating a leiomyoma from a uterine sarcoma is one part of the diagnostic process for all women with a uterine mass. The differential diagnosis of an enlarged uterus includes non-neoplastic conditions and benign and malignant neoplasms:
●Uterine adenomyoma or diffuse adenomyosis
●Uterine carcinosarcoma (considered an epithelial neoplasm)
●Metastatic neoplasm (typically from another reproductive tract primary)
●Endometrial processes that may enlarge the uterus – Endometrial polyp, endometrial hyperplasia, hematometra
The differential diagnosis of an enlarged uterus is discussed in detail separately. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Differential diagnosis'.)
PREVALENCE OF SARCOMA IN WOMEN UNDERGOING SURGERY FOR BENIGN INDICATIONS
Presumed benign leiomyomas — Uterine sarcoma is rare (3 to 7/100,000 United States women) . The rate of sarcoma in women with a symptomatic uterine mass (typically abnormal uterine bleeding) is higher, but the true prevalence in symptomatic women is unknown.
Unfortunately, there are no high-quality data regarding the prevalence of sarcoma in women planning surgery for presumed benign leiomyomas. There are many limitations to the data:
●Many studies are retrospective case series
●Many were conducted at referral centers and so may include a higher proportion of complex cases
●Preoperative evaluation with imaging and endometrial sampling was not performed in all patients
●Imaging techniques may have been less advanced in earlier studies
●Some studies included women diagnosed with sarcoma preoperatively (usually with endometrial sampling) so these were not intra- or postoperative diagnoses
●Some women with sarcoma had known risk factors (eg, older age, postmenopausal status)
In studies and systematic reviews of women undergoing hysterectomy or myomectomy for a myometrial mass, the prevalence of sarcoma is approximately 0.20 percent (1 in 500) in most studies or reviews, and estimates of the prevalence range from 0.05 (1 in 2000) to 0.28 percent (1 in 352) depending upon which studies are included or excluded [5-21]. The majority of cases reported were leiomyosarcoma, but these studies included a few cases of endometrial stromal sarcoma. The prevalence of leiomyosarcoma in this patient population is therefore likely slightly higher. Representative studies include:
●A meta-analysis including 64 prospective studies (5223 women) and 70 retrospective studies (24,970 women) of women who underwent surgery for presumed benign leiomyomas . The overall rate of leiomyosarcoma was 0.05 (1 in 2000) surgeries; in prospective studies, it was 0.01 percent (1 in 8300) surgeries, and in retrospective studies, it was 0.06 percent (1 in 1700) surgeries. There are several possible explanations for the significantly lower rate in the prospective studies. There may be less selection bias than in retrospective studies. Also, in the prospective study group, more than one-half of the studies were of women undergoing myomectomy, suggesting these women may be younger and/or have less clinical suspicion of malignant neoplasm.
●The largest study that evaluated unexpected malignant neoplasm of all types in women who underwent morcellation was a report from a United States insurance database, including 232,882 women who underwent minimally invasive (laparoscopic or robotic ) hysterectomy, which found that morcellation was performed in 36,470 (15.7 percent) . Among the women who had morcellation, there were 99 cases of uterine cancer including sarcomas and endometrial carcinomas (0.27 percent, 1 in 370), 39 uterine neoplasms of uncertain malignant potential, 368 cases of endometrial hyperplasia (most cases were without atypia (non-neoplastic) and thus not thought to have a premalignant phenotype ), and 26 other gynecologic malignant neoplasms. The prevalence of malignant neoplasm was 0.34 percent and of all neoplasms was 1.5 percent, although the clinical significance of endometrial hyperplasia without atypia is uncertain. Presence of malignant neoplasm was associated with increasing age; compared with women age 40 years, the prevalence ratios were: 50 to 54 years, 4.97; 55 to 59, 19.37; 60 to 64, 21.36; and ≥65, 35.97. In absolute numbers, the prevalence of cancer in this series for women under age 40 was 1/1500 and for women 40 to 44 was 1/1100. A limitation of the study was that the histology of the uterine malignant neoplasm cases was not reported. These data add support to limiting morcellation to premenopausal women, since 50 years old is approximately the average age of menopause.
●A population-based study for all uterine sarcomas from 2006 to 2013 from a health care system included 34,728 hysterectomies and reported a rate of occult uterine sarcoma of 0.36 percent (1 in 278) . In this study, risk was strongly related to age, with adjusted relative risk of 2.5 for women ages 50 to 59 and 12.8 for women ≥60 years compared with women 50 years and younger. However, because of the larger number of hysterectomies performed in younger women, 48 percent of occult sarcomas were diagnosed in the youngest age strata.
●A study of 4791 women in Norway undergoing surgery for presumed benign leiomyomas included 26 women who were diagnosed with leiomyosarcoma, but only six (0.1 percent) of these had no preoperative findings suspicious for malignant neoplasm; among the other women, six were diagnosed with leiomyosarcoma on endometrial biopsy prior to surgery and 14 had findings suspicious for malignant neoplasm and thus underwent open hysterectomy . The mean age of women with leiomyosarcoma (including a total of 26 women, some of whom had preoperative findings suspicious for malignancy) was 61 years and the majority were postmenopausal (70.4 percent).
●Another large study evaluated the finding of unexpected gynecologic malignant neoplasm in a population-based database that included 6360 women undergoing hysterectomy for benign indications, a broader population than those undergoing morcellation . The incidence of unexpected gynecologic malignant neoplasm was 2.7 percent, including ovarian, peritoneal, and fallopian tube carcinoma (1.1 percent); endometrial malignant neoplasm (1.0 percent); uterine sarcoma (0.2 percent); cervical carcinoma (0.2 percent); and metastatic malignant neoplasm (0.2 percent). Interestingly, in this study, there was no difference in mean age of women with an unexpected diagnosis of sarcoma compared with those with benign pathology (46.9 versus 47.0 years), although this was based on a total of 14 patients. In all patients with sarcoma, there was a pattern of increasing age (14 with benign preoperative indications and 10 with malignant preoperative indications): three were age <40 years, five were 40 to 49 years, and 16 were >50 years. Of the undiagnosed sarcomas (14 of 6360, or a risk of 0.2 percent, 1 in 454), nine had a diagnosis of abnormal uterine bleeding (and thus should have had further preoperative evaluation). Limitations of this study include that it did not provide data regarding risk factors for uterine malignant neoplasm (eg, Reed syndrome in young patients ), preoperative evaluation, or the surgical approach or technique (eg, laparoscopy, morcellation). It also did not specify whether the malignant neoplasm was discovered intraoperatively or on postoperative pathology, which are different clinical scenarios in terms of ability to perform an appropriate staging procedure and avoid tissue dissemination.
●A large single center study included 10,119 women who underwent hysterectomy for benign indications. Nine patients were found to have uterine sarcoma (0.09 percent, 1 in 1124) . The indication for hysterectomy in all women with occult sarcoma was abnormal uterine bleeding or pelvic mass.
●Regarding myomectomy, data from a national United States hospital database of 41,777 women undergoing myomectomy, including 3220 women who underwent myomectomy with electromechanical morcellation, reported that 0.43 percent had a pathologic finding (malignant neoplasm, neoplasms of uncertain malignant potential, or endometrial hyperplasia) and 0.09 percent had uterine cancer . Among all myomectomy patients, increasing age was significantly associated with an increased risk of uterine cancer. The risk of occult uterine cancer stratified by age was <40 years 1 in 2337, 40 to 49 years 1 in 702, 50 to 59 years 1 in 154, and ≥60 years 1 in 31. These data support the US Food and Drug Administration guidance that electromechanical morcellation should not be used in peri- and postmenopausal women with a uterine tumor.
Pelvic organ prolapse — Uterine sarcoma or other uterine cancer may be discovered in women after hysterectomy for pelvic organ prolapse. This is a challenging issue because these women do not usually have abnormal uterine bleeding and thus may not undergo endometrial sampling or pelvic imaging . However, these women may be less likely to have morcellation since the treatment of choice for most women would be a vaginal hysterectomy due to the prolapse and need for concomitant vaginal procedures to repair the prolapse. In a large study of this issue, among 1196 women who underwent hysterectomy for prolapse, malignant neoplasm was found postoperatively in 0.3 percent and endometrial hyperplasia in 0.6 percent . There were no specimens with sarcoma. Another study included 640 women who underwent hysterectomy for prolapse; three cases of malignant neoplasm were identified and one case was sarcoma .
CLINICAL FEATURES — Assessing clinical characteristics is the initial approach to evaluating a patient with a presumed leiomyoma in whom there is some concern of uterine sarcoma. Suspicion of sarcoma may change based upon a patient's risk factors or response to treatment. Unfortunately, the clinical features of benign leiomyomas and uterine sarcomas are often indistinguishable.
Risk factors — Uterine sarcoma is rare and risk factors are not well defined for uterine sarcomas in general or specifically for leiomyosarcoma. The known risk factors are summarized below and discussed in detail separately. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Epidemiology'.)
Common to both leiomyomas and sarcoma
Race — Black race is a risk factor for both uterine leiomyomas and uterine sarcoma. The relative risk and incidence of leiomyomas is two- to threefold greater in black women than in white women. The cumulative incidence of leiomyomas of any size, including very small tumors, by age 50 years is >80 percent for black women and almost 70 percent for white women . (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Prevalence'.)
Similarly, black women have an approximately twofold higher incidence of leiomyosarcomas (but not other types of uterine sarcoma) and carcinosarcoma than white women [4,32]. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Race'.)
Increasing age and postmenopausal status — Benign leiomyomas are responsive to gonadal steroids (estrogen and progesterone) and develop primarily in women of reproductive age, with symptoms developing on average as early as the 20s in black women and typically in the 30s or 40s in white women. Leiomyomas typically stabilize or diminish in size following menopause. Postmenopausal estrogen therapy may be associated with modest growth of myomas and/or persistent symptoms but does not appear to induce the development of new leiomyomas. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Prevalence' and "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Women on hormone therapy'.)
In contrast, increasing age is a significant risk factor for uterine sarcomas. The average age at diagnosis is 60 years; thus, the majority of sarcomas occur after menopause. Young age does not exclude the diagnosis of uterine sarcoma, however, since it has been reported in women as young as their mid-20s . As an example, in a study of uterine sarcoma cases from 2000 to 2012 in a United States cancer database, the incidence was more than fourfold higher in women ≥50 years old compared with younger women (6.4 versus 1.5 per 100,000) . (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Epidemiology'.)
Thus, for postmenopausal women, a new or growing uterine mass warrants further evaluation for uterine sarcoma. The level of suspicion may be lower in women who are on postmenopausal estrogen therapy and have a small increase in the size of a fibroid known to present prior to menopause. In this subgroup, a trial of discontinuing postmenopausal estrogen therapy is an option to see if regression occurs. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Women on hormone therapy'.)
The available evidence supports an increased risk of undetected malignant neoplasm in women 50 years or older who undergo morcellation of uterine tissue . (See 'Presumed benign leiomyomas' above.)
Tamoxifen — Long-term use of tamoxifen (five years or more) is associated with an increase in risk of developing uterine sarcoma. The absolute risk remains small (approximately 17/100,000 women) . In general, sarcomas present two to five years following the start of tamoxifen therapy and are often at an advanced stage at diagnosis [35,36]. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Tamoxifen'.)
Other risk factors — Other risk factors that are associated with uterine sarcoma, but not with leiomyomas, include pelvic irradiation, a history of childhood retinoblastoma, and hereditary leiomyomatosis and renal cell carcinoma syndrome. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Pelvic radiation' and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Hereditary conditions'.)
Data are inconclusive regarding parity and time of menarche and menopause as risk factors for sarcoma. For benign leiomyomas, early menarche (<10 years old) is a risk factor (particularly in black women), and parity decreases the chances of fibroid formation. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Prevalence' and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Other risk factors'.)
Signs and symptoms — Abnormal uterine bleeding, pelvic pain/pressure, and a pelvic mass are the primary presenting symptoms and signs for both leiomyomas and sarcoma, making it difficult to differentiate between the two on this basis [33,37-39]. Some women with sarcoma present with a foul-smelling vaginal discharge, but this is not a reliable indicator of malignant neoplasm since vaginal discharge is a common gynecologic symptom. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Clinical features' and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Clinical presentation'.)
Clinical manifestations associated with metastatic neoplasm may be found in women with sarcoma but not with ordinary leiomyomas. Uterine sarcomas spread via intra-abdominal, lymphatic, or hematogenous routes. Hematogenous spread is most often to the lungs. Of note, some histologically benign leiomyoma variants also disseminate and must be excluded if widespread disease is found. (See "Variants of uterine leiomyomas (fibroids)", section on 'Benign uterine variants with extrauterine disease' and "Treatment and prognosis of uterine leiomyosarcoma" and "Classification and treatment of endometrial stromal sarcoma and uterine adenosarcoma".)
Failure to respond to treatment — Failure to respond to medical treatment (gonadotropin-releasing hormone agonist treatment) or nonexcisional procedures for leiomyomas, such as uterine artery embolization, has preceded a diagnosis of malignancy in multiple reports [40-46]. However, such treatment failures are not definitive evidence of malignant neoplasm.
The concept of failure to respond to hormonal treatment has been proposed as a method of differentiating between uterine leiomyomas and sarcoma. This approach has not proved useful, however, since the few data regarding this approach are mixed, with one report of shrinkage in a leiomyosarcoma .
While it is possible that failure to respond to other nonexcisional therapies such as magnetic resonance-guided focused ultrasound (MRgFUS) also raises the possibility of sarcomas, the only report to date led to surgery rather than MRgFUS for a suspected sarcoma due to suspicious pretreatment imaging .
DIAGNOSTIC METHODS — Uterine sarcoma is a histologic diagnosis based upon pathology evaluation after resection of uterine tissue (myomectomy or hysterectomy). Uterine sarcomas are most commonly diagnosed following surgery for presumed leiomyomas. (See 'Presumed benign leiomyomas' above.)
Preoperative and intraoperative findings are of limited value in estimating the likelihood that a mass is a uterine sarcoma. Magnetic resonance imaging (MRI) and endometrial sampling are the most potentially useful techniques.
Pelvic examination — A thorough pelvic examination should be performed in all women with a pelvic mass. The size, contour, and mobility of the uterus should be noted, along with any other findings (eg, adnexal mass, cervical mass, or vaginal nodules). These findings are helpful to follow changes in the uterus over time and/or to aid surgical planning. A fixed mass is more suggestive of a malignant neoplasm than a mobile mass. However, this is not pathognomonic, since a malignant neoplasm that has not invaded the uterine serosa may be mobile, and a mass associated with endometriosis or pelvic infection may be fixed. Unfortunately, there are no examination findings that can distinguish a leiomyoma from a uterine sarcoma.
Screening and evaluation for gynecologic malignancies — Prior to treatment for presumed leiomyomas, women should undergo routine screening for cervical neoplasm. (See "Screening for cervical cancer".)
Evaluation of abnormal uterine bleeding is of critical importance to exclude endometrial hyperplasia or carcinoma. A full menstrual history and a history of risk factors for endometrial carcinoma (including Lynch syndrome) should be elicited. Pelvic imaging or endometrial sampling (table 1) should be performed if appropriate. (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women" and "Postmenopausal uterine bleeding".)
Choice of imaging modality — There is no pelvic imaging modality that can reliably differentiate between benign leiomyomas and uterine sarcomas. Leiomyomas and uterine sarcomas appear similar; both are focal masses within the uterus and both can have central necrosis. Pelvic ultrasound followed by MRI is the most useful imaging strategy.
Pelvic ultrasound is typically the first-line study to evaluate women for potential uterine pathology. Sonographic evaluation of a uterine mass may identify features suggestive of sarcoma (mixed echogenic and poor echogenic parts; central necrosis; and color Doppler findings of irregular vessel distribution, low impedance to flow, and high peak systolic velocity); however, many of these characteristics may also be found in benign leiomyomas .
MRI may be helpful in women in whom there is a suspicion of sarcoma; however, it does not provide a definitive diagnosis. High signal intensity is not a reliable indicator of uterine sarcoma . A consistent finding in leiomyosarcomas is the absence of calcifications . Calcifications suggest that the mass has undergone necrosis. This is most typically seen in fibroids that have outgrown their blood supply (for example, postpartum or after uterine artery embolization) or in postmenopausal women as blood flow to the uterus regresses. Some data suggest that ill-defined margins are consistent with a sarcoma . Two small studies using different techniques of MRI with gadolinium contrast have reported specificities of 93 to 100 percent and positive predictive values of 53 to 100 percent [51,52]. Diffusion weighted MRI also appears to differentiate ordinary and degenerated leiomyomas from sarcomas and cellular leiomyomas . Finally, the presence of intralesional hemorrhage appears to be suggestive of sarcoma [47,54]. Further study of use of MRI for this purpose is needed.
Computed tomography (CT) does not reliably differentiate between leiomyomas and uterine sarcomas .
Positron emission tomography/CT with fluorodeoxyglucose (FDG) does not appear to be useful to distinguish between leiomyomas and uterine sarcomas. While the FDG uptake is generally high in sarcomas and low in leiomyomas, the uptake varies across individual tumors .
Despite the limitations of pelvic imaging, however, we suggest that women with a pelvic mass that is newly diagnosed or has changed markedly in size or mobility undergo a pelvic ultrasound as an initial imaging study to exclude other etiologies of uterine enlargement. If uterine sarcoma is suspected based upon clinical characteristics of the patient or mass or upon sonographic findings, MRI with gadolinium contrast may aid in assessing the likelihood of malignancy.
Findings that do NOT reliably predict sarcoma
Rapidly growing uterine mass — Historically, the common teaching had been that rapid growth of a uterine mass (eg, increasing by six weeks' gestational size within one year ) is a sign of a potential uterine sarcoma. However, it appears that most women with a rapidly enlarging uterus or uterine mass do NOT have a sarcoma.
This concept of a rapidly growing uterine mass as a sign of a potential sarcoma appears to date back to the era when pelvic examinations alone were used to assess uterine size . With modern pelvic imaging, there is an increased appreciation that, in women of reproductive age, leiomyomas both grow and shrink and do so at differing rates within the same woman [58-61]. Research on normal leiomyomas shows that growth of up to 138 percent can occur within six months . As an example, in a prospective study, 101 fibroids in 36 women were evaluated with MRI at three-month intervals for one year . Increase in volume of ≥30 percent in a three-month period was found in 37 myomas; rapid growth was more likely in tumors that were ≤5 cm in diameter. (See "Uterine leiomyomas (fibroids): Epidemiology, clinical features, diagnosis, and natural history", section on 'Natural history'.)
Rapid growth may occur in either a sarcoma or a benign leiomyoma. In addition, it is theoretically possible for a sarcoma to remain indolent for a long period of time and only come to diagnostic attention when a more aggressive phase of disease is entered.
The teaching about rapid growth of a uterine mass being associated with an increased risk of uterine sarcoma was not substantiated in a study of 1332 women who underwent hysterectomy or myomectomy of presumed uterine leiomyomas . The incidence of uterine sarcoma was low for all women, with a similar incidence in the 371 women with a rapidly growing uterus by clinical or ultrasound examination (one uterine sarcoma, 0.27 percent) and in the 961 without rapid uterine growth (two uterine sarcomas, 0.15 percent). In addition, a literature review of 26 studies found that a history of rapid uterine enlargement was documented in only 15 of 580 patients (2.6 percent) with uterine sarcomas . Thus, the great majority of premenopausal women with a rapidly enlarging uterus or uterine mass do not have a sarcoma.
In contrast, because leiomyomas are stimulated by estrogen and progesterone, postmenopausal women who have a uterine mass that is new or is growing at either a slow or rapid pace should be evaluated for malignancy. The level of suspicion for uterine sarcoma is lower in women who are on postmenopausal estrogen therapy and have a small increase in the size of a presumed fibroid known to have been present prior to menopause. (See 'Increasing age and postmenopausal status' above.)
Large or solitary uterine mass — Retrospective studies have reported that a sarcoma is often the largest (or the only) mass within a uterus, averaging 7 to 9 cm in diameter [33,37,62,63]. However, leiomyomas may also be singular and may be of any size. Although data are limited, large uterine size (in excess of 20 gestational weeks) has also not been shown to be associated with sarcoma risk [33,64]. As a result, these features are not useful in identifying malignancy.
Biopsy — Endometrial sampling can detect some uterine sarcomas as well as evaluate women for endometrial neoplasm. Preoperative imaging-guided biopsy of the mass is generally not performed because of sampling errors, but intraoperative biopsy or frozen section is indicated if there are suspicious findings during surgery.
Endometrial sampling — Endometrial sampling yields a preoperative diagnosis in approximately 33 to 68 percent of women with uterine sarcomas [65,66]. The method of endometrial sampling (office endometrial biopsy or dilation and curettage) does not appear to impact the sensitivity of the test.
There are few data regarding use of endometrial sampling in women with sarcoma. Representative studies include:
●The largest study includes data from the Canadian Task Force III database . Among women with leiomyosarcoma who underwent endometrial sampling before surgery (n = 68), the sensitivity for a diagnosis of features of a malignant smooth muscle neoplasms was 52 percent (leiomyosarcoma 35 percent and other features suspicious for malignancy 16 percent). There was no significant difference in the performance of the test between office endometrial biopsy and dilation and curettage.
●In a small study, among women with leiomyosarcoma, three of eight (38 percent]) who underwent preoperative endometrial sampling had a correct diagnosis .
●In another small study, the sensitivity of endometrial sampling for a diagnosis of leiomyosarcoma was four of six women (67 percent) and for a diagnosis of endometrial stromal sarcoma was two of six women (33 percent). Two additional women with leiomyosarcoma and two with endometrial stromal sarcoma had preoperative pathology results reported as malignant neoplasm but an incorrect histologic diagnosis (including endometrial carcinoma, stromal sarcoma, and other sarcoma . Thus, these women would have been managed surgically as appropriate for a malignancy. There was no significant difference in the performance of the test between office endometrial biopsy and dilation and curettage.
Since endometrial biopsy is a minimally invasive procedure and is already indicated in many women with abnormal uterine bleeding to exclude endometrial neoplasia, we suggest endometrial sampling in women in whom sarcoma is suspected or for whom the planned procedure includes intraperitoneal morcellation. Morcellation disrupts the specimen and potentially disseminate malignant neoplasm. (See "Uterine tissue extraction by morcellation: Techniques and clinical issues", section on 'Tissue dissemination and worsened prognosis'.)
Use of minimally invasive needle biopsy of a uterine mass (guided by pelvic imaging or laparoscopy) has been proposed but is not typically performed. Limitations of this method are that the accurate diagnosis of sarcoma requires sampling of multiple sites and that the procedure may spill malignant cells within the peritoneal cavity.
Other tests — There are no laboratory tests that have been found to help differentiate uterine leiomyomas from sarcoma. Some reports have mentioned use of lactate dehydrogenase (LDH), LDH isozyme 3, or cancer antigen 125 . However, there are no high-quality data supporting their clinical use.
Intraoperative evaluation — During myomectomy or hysterectomy, some characteristics of a uterine mass may raise suspicion of malignancy. Frozen section analysis cannot definitively diagnose or exclude uterine sarcoma.
Gross characteristics of the mass — During excisional surgery (ie, myomectomy), uterine sarcomas may appear or feel different than leiomyomas. Potential features of sarcomas compared with leiomyomas include (picture 1) [70-72]:
●Loss of the typical whorl pattern.
●Absence of a bulging surface when the capsule is incised.
●Ill-defined margins – The mass may be difficult to excise, although this may also be true of an adenomyoma or certain leiomyomas (eg, due to degenerative change or prior treatment with a gonadotropin-releasing hormone agonist or antagonist).
Detection of such characteristics may raise the suspicion of a sarcoma but should not be the sole reason for proceeding with an unplanned hysterectomy. These differences are subtle, and their identification relies upon adequate surgical experience with ordinary leiomyomas.
Frozen section — Frozen section analysis is not reliable for excluding uterine sarcoma [9,37,73]. Multiple areas must be sampled to obtain an accurate diagnosis, while frozen section analysis typically depends upon a limited tissue sample. Thus, there is a high likelihood of a false-negative result even if a sarcoma is present. Only a definitive diagnosis of sarcoma on frozen section should influence surgical decisions (eg, whether to perform hysterectomy or staging). (See 'Should unplanned hysterectomy be performed based on intraoperative findings?' below.)
Postoperative pathology evaluation — Criteria are important to the diagnosis of uterine sarcomas: mitotic index, cellular atypia, cellularity, and geographic areas of coagulative necrosis separated from viable neoplasm [72,74]. The more features exhibited by the lesion, the more likely it is to have clinically aggressive behavior [72,74]. There are a number of pathologic entities in which lesions display some, but not all, of the facets of malignant neoplasm. (See "Variants of uterine leiomyomas (fibroids)", section on 'Smooth muscle tumors of uncertain malignant potential'.)
Diagnosis requires examination of multiple sites in the mass . Features of the gross appearance of the tissue, including the color, consistency, and variegation of the incised surface, can help guide sampling of tissue for microscopic examination.
Do techniques that disrupt a mass disseminate tissue and worsen prognosis? — Surgical techniques such as myomectomy, intraperitoneal morcellation, and supracervical hysterectomy disrupt a uterine specimen. Infrequently, an occult uterine cancer is diagnosed postoperatively and, in such cases, there is a concern that malignant cells may have been disseminated or remain in uterine or cervical tissue that was not removed. In addition, dissemination of benign leiomyomatous tissue may result in benign tissue implants that require further treatment . (See "Variants of uterine leiomyomas (fibroids)".)
Disruption of the specimen appears to worsen prognosis of uterine cancer, but there are few data, and the comparative risk of the specific surgical methods (electromechanical morcellation, scalpel morcellation, supracervical hysterectomy, or myomectomy) is uncertain [17,76-79].
Morcellation — Morcellation of uterine tissue (cutting tissue into pieces to remove through a small incision) is performed in some procedures to allow removal of a large tissue block through a small laparoscopic or vaginal incision. This may be performed using an electromechanical morcellator device, as is commonly done during laparoscopy, or with a scalpel, commonly done during vaginal hysterectomy. The risk of dissemination of tissue and other risks during morcellation is discussed in detail separately. (See "Uterine tissue extraction by morcellation: Techniques and clinical issues".)
Supracervical hysterectomy — Supracervical hysterectomy is typically performed either via laparotomy or laparoscopy. With laparotomy, the specimen is not usually morcellated, so the only tissue disruption is the incision to amputate the uterine cervix. With laparoscopy, the specimen is typically morcellated, which likely results in greater tissue dissemination. (See "Uterine tissue extraction by morcellation: Techniques and clinical issues".)
There are few data about the risk of neoplasm dissemination and worsened prognosis with supracervical hysterectomy. The only study to address this issue included 12 women with endometrial carcinoma or uterine sarcoma who underwent supracervical hysterectomy without morcellation; 9 of 12 underwent subsequent surgery for restaging, and none were upstaged . The study also included women who underwent morcellation for hysterectomy or myomectomy; four of five underwent restaging surgery, and two of these four were upstaged.
Myomectomy — Myomectomy is a uterine-sparing procedure in which only the leiomyomas are removed. Intraperitoneal myomectomy is performed via laparotomy or laparoscopy. With laparotomy, the specimen(s) are not usually morcellated, but there may be multiple fibroids, and there is usually substantial exposure of myometrial tissue. With laparoscopy, the specimen is typically morcellated. Smooth muscle cells have been found in pelvic washing after myomectomy and morcellation .
There are few data about the risk of neoplasm dissemination and worsened prognosis with myomectomy. No studies have examined women who underwent myomectomy without morcellation. One retrospective cohort study of 30 women with uterine sarcoma diagnosed postoperatively who underwent myomectomy with morcellation (electromechanical or scalpel morcellation) were compared with women who underwent total hysterectomy . At five years, there were no significant differences in recurrence-free survival (24 versus 46 percent) or overall survival rate (38 versus 43 percent), but the trend was toward a lower rate with myomectomy combined with morcellation.
Should hysterectomy be performed to exclude uterine sarcoma? — For most premenopausal women with presumed uterine leiomyomas, whether asymptomatic or symptomatic, we recommend not performing hysterectomy for the sole purpose of excluding malignant neoplasm. Reasonable exceptions to this are women with endometrial sampling and/or magnetic resonance imaging (MRI) results that strongly suggest sarcoma, those with thoracic imaging consistent with lung metastases, those with constitutional symptoms suggestive of malignancy, or those with multiple risk factors for uterine sarcoma.
The best clinical estimate of the likelihood of uterine sarcoma depends upon a constellation of factors. Unfortunately, preoperative and intraoperative findings are of limited value in diagnosing a uterine sarcoma. Factors that may raise a suspicion of sarcoma include symptoms, risk factors, failure of response to prior therapy, and the findings of MRI and endometrial sampling. (See 'Risk factors' above and 'Failure to respond to treatment' above and 'Choice of imaging modality' above and 'Endometrial sampling' above.)
In the rare cases in which a woman presents with a uterine mass and symptoms of lung lesions (eg, dyspnea), evidence of lung metastases on thoracic imaging greatly increases the likelihood of a malignant process. However, benign metastasizing leiomyomas is a benign condition that may also present with lung lesions. (See "Variants of uterine leiomyomas (fibroids)", section on 'Benign metastasizing leiomyomas'.)
Asymptomatic women — Hysterectomy should not be performed in most women with asymptomatic presumed leiomyomas for the sole purpose of excluding a uterine sarcoma.
The most important factor in such decisions is the rarity of uterine sarcoma. The likelihood of finding sarcoma in women with a preoperative diagnosis of leiomyomas has been consistently reported in observational studies of 1000 or more women as approximately 0.2 percent [7-16]. These data are from symptomatic women, so the risk is likely much lower in asymptomatic women. This risk is much lower than the risk of severe complications associated with hysterectomy (3.5 to 11.0 percent) for benign disease found in studies of 1000 to 30,000 hysterectomies [83,84]. This recommendation is in agreement with the American College of Obstetricians and Gynecologists, which advises that there is insufficient evidence to support hysterectomy for asymptomatic leiomyomas solely to rule out malignancy .
Given these data, the risk of a missed diagnosis of sarcoma in a small number of women does not appear to outweigh exposing significantly more women to the risks of unnecessary hysterectomy. In our practice, the primary exceptions we make to this are for women in whom endometrial sampling and/or MRI strongly suggests sarcoma or those with thoracic imaging consistent with lung metastases. Hysterectomy is also a reasonable option for women with multiple risk factors for uterine sarcoma. (See 'Risk factors' above and 'Choice of imaging modality' above and 'Endometrial sampling' above.)
Following the detection of presumed uterine fibroids in an asymptomatic woman, there are no high-quality data to guide follow-up. We order an initial imaging study (usually an ultrasound) to confirm that a pelvic mass is consistent with a fibroid rather than with other etiologies (eg, ovarian mass). After this initial evaluation, we perform annual pelvic examinations. If the characteristics of the uterus change or symptoms develop, we proceed with further evaluation and patient counseling regarding treatment options. (See "Overview of treatment of uterine leiomyomas (fibroids)", section on 'Expectant management'.)
Symptomatic women — For women with symptomatic presumed leiomyomas, hysterectomy is one of several treatment options. The best treatment option should be chosen based upon the patient's symptoms, findings on evaluation, plans for future pregnancies, and patient preferences.
The advantage of hysterectomy is that it prevents the formation of new fibroids and also can treat concomitant problems such as adenomyosis, endometriosis, and cervical neoplasia. The disadvantages are loss of fertility, risk of surgical complications, the time needed for recovery, and risk of long-term morbidity and earlier menopause, especially if the ovaries are removed at the time of hysterectomy [86-88]. In some women, the question may arise of whether to choose hysterectomy in order to exclude malignancy rather than a conservative treatment. (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy".)
As with women with asymptomatic presumed leiomyomas, for most women with a symptomatic uterine mass, we recommend not choosing hysterectomy rather than other treatments based solely upon the goal of excluding malignant neoplasm. Reasonable exceptions to this are women with endometrial sampling and/or MRI results that strongly suggest sarcoma, thoracic imaging consistent with lung metastases, or multiple risk factors for uterine sarcoma.
On the other hand, for women deciding between several options for treatment of symptomatic fibroids, excluding malignant neoplasm may be a potential benefit of hysterectomy. As noted above, uterine sarcoma is rare, but the prevalence is greater in symptomatic than asymptomatic women. Nonetheless, the risk of a complication of hysterectomy exceeds the risk of finding an undiagnosed malignant neoplasm . In addition, women who fail to respond to conservative therapy may have an increased risk of sarcoma and also may require definitive treatment. Thus, excluding malignancy may be one factor that influences the decision regarding whether to choose treatment with hysterectomy. (See 'Risk factors' above and 'Failure to respond to treatment' above and 'Choice of imaging modality' above and 'Endometrial sampling' above.)
Should unplanned hysterectomy be performed based on intraoperative findings? — During myomectomy or other pelvic surgery, a surgeon may encounter findings suggestive of a uterine sarcoma. Intraoperative findings rarely indicate the need for an unplanned hysterectomy, and sending pathology samples for evaluation and planning a potential second surgery pending the results is usually prudent, especially for women who desire future childbearing. It is prudent to include, at the time of preoperative consent, discussion of plans in the event of diagnosing a malignant neoplasm intraoperatively based on the updated guidance from the US Food and Drug Administration. Gross characteristics of a tumor may be suggestive of sarcoma but are not diagnostic. Frozen section analysis is often inconclusive. (See 'Intraoperative evaluation' above.)
The only indications for hysterectomy are a definitive frozen section diagnosis of sarcoma and/or gross evidence of metastases. One note of caution is that women with apparent intra-abdominal metastases may have a primary neoplasm at another site or leiomyomatosis peritonealis disseminata, which is a rare and benign condition. Unplanned hysterectomy should not be performed in women of reproductive age without a pathologic diagnosis of sarcoma. Additionally, because oophorectomy has not been shown to influence prognosis for leiomyosarcomas, ovarian preservation may be carried out in the case of unexpected intraoperative findings of sarcoma . (See "Variants of uterine leiomyomas (fibroids)", section on 'Leiomyomatosis peritonealis disseminata'.)
Staging for an incidentally discovered intra-abdominal malignancy is best performed by a surgeon experienced in these procedures. (See "Abdominal hysterectomy", section on 'Malignancy'.)
Do leiomyomas progress to sarcoma? — In general, it appears that uterine sarcomas do not arise from benign leiomyomas, with rare exceptions. The consensus from genetic studies has been that most sarcomas arise independently . Sarcomas typically have complex karyotypes and aneuploidy, while leiomyomas have characteristic rearrangements, many of which are shared by other benign neoplasms . Intermediate forms between these two patterns had not been described.
Histologic studies have found rare examples that appear consistent with progression from a leiomyoma to sarcoma . The most compelling evidence comes from a rare subgroup of leiomyomas with cellular or atypical histology based upon data from two clinical and two molecular genetic studies [92-95]. In a clinical study, 3 of 18 women with cellular or atypical variants died of their disease . There was a longer latency between diagnosis and death in these patients compared with those with leiomyosarcoma (>6 years versus median of 2.1 years). There are no data regarding how often cellular or atypical histology are associated with such abnormal clinical behavior. (See "Variants of uterine leiomyomas (fibroids)", section on 'Benign histologic variants of leiomyomas'.)
CLINICAL APPROACH — The approach to women with presumed benign leiomyomas in different clinical categories is discussed in this section. All women with a uterine mass should be screened for premenopausal status, gynecologic malignancies, and sarcoma risk factors and undergo appropriate testing based on this screening.
Women managed expectantly — Unless risk factors are identified, women may be managed expectantly within guidelines for routine care unless new symptoms develop.
Women on medical therapy — Women should be re-evaluated for possible sarcoma if they fail to respond to medical therapy, new symptoms appear, or symptoms worsen while on medical therapy or at least annually, with frequency of visit determined based on the particular medical therapy they are on.
Women planned for surgery — Discussion of a woman's plans for future childbearing and the full range of fibroid treatment options should be discussed. The possibility of finding an unanticipated malignant neoplasm should be discussed, and only if future childbearing is not desired, discussion can take place regarding proceeding with hysterectomy if suspicious frozen section pathology is found.
Women planned for imaging-based procedures — Most women in this category should have screening with magnetic resonance imaging and should be counseled to go in the direction of surgical therapy if suspicious findings are present. The woman's plans for future childbearing and the full range of fibroid treatment options should be discussed.
SUMMARY AND RECOMMENDATIONS
●Benign uterine leiomyomas (fibroids) are the most common pelvic neoplasm in women (lifetime risk 70 to 80 percent). Uterine sarcoma is rare (3 to 7/100,000 in the United States population). The likelihood of finding a sarcoma in a population of women with an intrauterine mass, some of whom have risk factors for uterine sarcomas, is approximately 0.1 to 0.28 percent.(See 'Introduction' above and 'Presumed benign leiomyomas' above.)
●Clinical manifestations are not useful to distinguish between leiomyomas and uterine sarcomas, since both typically present with abnormal uterine bleeding, pelvic pain/pressure, and a pelvic mass. (See 'Signs and symptoms' above.)
●A rapidly enlarging uterine mass is not a reliable sign of a uterine sarcoma in women of reproductive age. After menopause, on the other hand, a new or growing uterine mass warrants further evaluation. Postmenopausal hormone therapy may cause a small increase in the size of an existing leiomyoma. (See 'Rapidly growing uterine mass' above and 'Increasing age and postmenopausal status' above.)
●Large uterine size (in excess of 20 gestational weeks) has not been shown to be associated with increased uterine sarcoma risk. (See 'Large or solitary uterine mass' above.)
●Endometrial sampling may detect uterine sarcoma in some patients. We suggest endometrial sampling for women with a uterine mass and who have signs, symptoms, risk factors, or other findings that raise suspicion of uterine sarcoma or endometrial carcinoma or for whom the planned procedure includes intraperitoneal morcellation. (See 'Endometrial sampling' above.)
●There is no pelvic imaging modality that can reliably differentiate between benign leiomyomas and uterine sarcomas. We suggest that women with a pelvic mass that is newly diagnosed or has changed markedly in size or mobility undergo a pelvic ultrasound as an initial imaging study rather than no imaging or imaging with another modality. (See 'Imaging' above.)
●Magnetic resonance imaging (MRI) with contrast may be helpful in women in whom there is a suspicion of sarcoma; however, it does not provide a definitive diagnosis. For women in whom uterine sarcoma is suspected based upon characteristics of the patient or mass or upon ultrasound findings, we suggest follow-up imaging with MRI rather than imaging with ultrasound alone or with other modalities. (See 'Imaging' above.)
●For most women with presumed uterine leiomyomas, whether asymptomatic or symptomatic, we recommend NOT performing hysterectomy for the sole purpose of excluding malignant neoplasm (Grade 1B). Reasonable exceptions to this are women with endometrial sampling and/or MRI results that strongly suggest sarcoma, those with thoracic imaging consistent with lung metastases, or those with multiple risk factors for uterine sarcoma. (See 'Asymptomatic women' above and 'Symptomatic women' above.)
●Leiomyomas do not appear to progress to sarcoma, with the exception of rare atypical or cellular variants. (See 'Do leiomyomas progress to sarcoma?' above.)
- Baird DD, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003; 188:100.
- Buttram VC Jr, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril 1981; 36:433.
- Serden SP, Brooks PG. Treatment of abnormal uterine bleeding with the gynecologic resectoscope. J Reprod Med 1991; 36:697.
- Brooks SE, Zhan M, Cote T, Baquet CR. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol Oncol 2004; 93:204.
- Pritts EA, Vanness DJ, Berek JS, et al. The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis. Gynecol Surg 2015; 12:165.
- http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM404148.pdf (Accessed on November 24, 2014).
- Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994; 83:414.
- Leung F, Terzibachian JJ, Gay C, et al. [Hysterectomies performed for presumed leiomyomas: should the fear of leiomyosarcoma make us apprehend non laparotomic surgical routes?]. Gynecol Obstet Fertil 2009; 37:109.
- Leibsohn S, d'Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol 1990; 162:968.
- Takamizawa S, Minakami H, Usui R, et al. Risk of complications and uterine malignancies in women undergoing hysterectomy for presumed benign leiomyomas. Gynecol Obstet Invest 1999; 48:193.
- Leung F, Terzibachian JJ. Re: "The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma". Gynecol Oncol 2012; 124:172.
- Durand-Réville M, Dufour P, Vinatier D, et al. [Uterine leiomyosarcomas: a surprising pathology. Review of the literature. Six case reports]. J Gynecol Obstet Biol Reprod (Paris) 1996; 25:710.
- Seidman MA, Oduyebo T, Muto MG, et al. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms. PLoS One 2012; 7:e50058.
- Theben JU, Schellong AR, Altgassen C, et al. Unexpected malignancies after laparoscopic-assisted supracervical hysterectomies (LASH): an analysis of 1,584 LASH cases. Arch Gynecol Obstet 2013; 287:455.
- Sinha R, Hegde A, Mahajan C, et al. Laparoscopic myomectomy: do size, number, and location of the myomas form limiting factors for laparoscopic myomectomy? J Minim Invasive Gynecol 2008; 15:292.
- Hagemann IS, Hagemann AR, LiVolsi VA, et al. Risk of occult malignancy in morcellated hysterectomy: a case series. Int J Gynecol Pathol 2011; 30:476.
- Park JY, Park SK, Kim DY, et al. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol 2011; 122:255.
- Kamikabeya TS, Etchebehere RM, Nomelini RS, Murta EF. Gynecological malignant neoplasias diagnosed after hysterectomy performed for leiomyoma in a university hospital. Eur J Gynaecol Oncol 2010; 31:651.
- http://www.aagl.org/wp-content/uploads/2014/05/Tissue_Extraction_TFR.pdf (Accessed on August 08, 2016).
- US Food and Drug Administration (FDA), Obstetrics and Gynecology Devices Advisory Committee. FDA executive summary: Laparoscopic power morcellation during uterine surgery for fibroids, Washington, DC 2014. http://www.fda.gov/advisorycommittees/calendar/ucm400221.htm (Accessed on July 10, 2014).
- Mahnert N, Morgan D, Campbell D, et al. Unexpected gynecologic malignancy diagnosed after hysterectomy performed for benign indications. Obstet Gynecol 2015; 125:397.
- Wright J, Columbia University, 2014, personal communication.
- Wright JD, Tergas AI, Burke WM, et al. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA 2014; 312:1253.
- Raine-Bennett T, Tucker LY, Zaritsky E, et al. Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation. Obstet Gynecol 2016; 127:29.
- Lieng M, Berner E, Busund B. Risk of morcellation of uterine leiomyosarcomas in laparoscopic supracervical hysterectomy and laparoscopic myomectomy, a retrospective trial including 4791 women. J Minim Invasive Gynecol 2015; 22:410.
- Stewart EA, Morton CC. The genetics of uterine leiomyomata: what clinicians need to know. Obstet Gynecol 2006; 107:917.
- Kho KA, Lin K, Hechanova M, Richardson DL. Risk of Occult Uterine Sarcoma in Women Undergoing Hysterectomy for Benign Indications. Obstet Gynecol 2016; 127:468.
- Wright JD, Tergas AI, Cui R, et al. Use of Electric Power Morcellation and Prevalence of Underlying Cancer in Women Who Undergo Myomectomy. JAMA Oncol 2015; 1:69.
- Ramm O, Gleason JL, Segal S, et al. Utility of preoperative endometrial assessment in asymptomatic women undergoing hysterectomy for pelvic floor dysfunction. Int Urogynecol J 2012; 23:913.
- Ackenbom MF, Giugale LE, Wang Y, Shepherd JP. Incidence of Occult Uterine Pathology in Women Undergoing Hysterectomy With Pelvic Organ Prolapse Repair. Female Pelvic Med Reconstr Surg 2016; 22:332.
- Wan OY, Cheung RY, Chan SS, Chung TK. Risk of malignancy in women who underwent hysterectomy for uterine prolapse. Aust N Z J Obstet Gynaecol 2013; 53:190.
- Hosh M, Antar S, Nazzal A, et al. Uterine Sarcoma: Analysis of 13,089 Cases Based on Surveillance, Epidemiology, and End Results Database. Int J Gynecol Cancer 2016; 26:1098.
- Giuntoli RL 2nd, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol 2003; 89:460.
- Wickerham DL, Fisher B, Wolmark N, et al. Association of tamoxifen and uterine sarcoma. J Clin Oncol 2002; 20:2758.
- Wysowski DK, Honig SF, Beitz J. Uterine sarcoma associated with tamoxifen use. N Engl J Med 2002; 346:1832.
- Moinfar F, Azodi M, Tavassoli FA. Uterine sarcomas. Pathology 2007; 39:55.
- Schwartz LB, Diamond MP, Schwartz PE. Leiomyosarcomas: clinical presentation. Am J Obstet Gynecol 1993; 168:180.
- Dinh TA, Oliva EA, Fuller AF Jr, et al. The treatment of uterine leiomyosarcoma. Results from a 10-year experience (1990-1999) at the Massachusetts General Hospital. Gynecol Oncol 2004; 92:648.
- Tsikouras P, Liberis V, Galazios G, et al. Uterine sarcoma: a report of 57 cases over a 16-year period analysis. Eur J Gynaecol Oncol 2008; 29:129.
- Meyer WR, Mayer AR, Diamond MP, et al. Unsuspected leiomyosarcoma: treatment with a gonadotropin-releasing hormone analogue. Obstet Gynecol 1990; 75:529.
- Joyce A, Hessami S, Heller D. Leiomyosarcoma after uterine artery embolization. A case report. J Reprod Med 2001; 46:278.
- Common AA, Mocarski EJ, Kolin A, et al. Therapeutic failure of uterine fibroid embolization caused by underlying leiomyosarcoma. J Vasc Interv Radiol 2001; 12:1449.
- D'Angelo A, Amso NN, Wood A. Uterine leiomyosarcoma discovered after uterine artery embolisation. J Obstet Gynaecol 2003; 23:686.
- Loong EP, Wong FW. Uterine leiomyosarcoma diagnosed during treatment with agonist of luteinizing hormone-releasing hormone for presumed uterine fibroid. Fertil Steril 1990; 54:530.
- Papadia A, Salom EM, Fulcheri E, Ragni N. Uterine sarcoma occurring in a premenopausal patient after uterine artery embolization: a case report and review of the literature. Gynecol Oncol 2007; 104:260.
- Milman D, Zalel Y, Biran H, et al. Unsuspected uterine leiomyosarcoma discovered during treatment with a gonadotropin-releasing hormone analogue: a case report and literature review. Eur J Obstet Gynecol Reprod Biol 1998; 76:237.
- Samuel A, Fennessy FM, Tempany CM, Stewart EA. Avoiding treatment of leiomyosarcomas: the role of magnetic resonance in focused ultrasound surgery. Fertil Steril 2008; 90:850.e9.
- Amant F, Coosemans A, Debiec-Rychter M, et al. Clinical management of uterine sarcomas. Lancet Oncol 2009; 10:1188.
- Van den Bosch T, Coosemans A, Morina M, et al. Screening for uterine tumours. Best Pract Res Clin Obstet Gynaecol 2012; 26:257.
- Schwartz LB, Zawin M, Carcangiu ML, et al. Does pelvic magnetic resonance imaging differentiate among the histologic subtypes of uterine leiomyomata? Fertil Steril 1998; 70:580.
- Goto A, Takeuchi S, Sugimura K, Maruo T. Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus. Int J Gynecol Cancer 2002; 12:354.
- Tanaka YO, Nishida M, Tsunoda H, et al. Smooth muscle tumors of uncertain malignant potential and leiomyosarcomas of the uterus: MR findings. J Magn Reson Imaging 2004; 20:998.
- Tamai K, Koyama T, Saga T, et al. The utility of diffusion-weighted MR imaging for differentiating uterine sarcomas from benign leiomyomas. Eur Radiol 2008; 18:723.
- Stewart EA, Marsh EE, Spies JB. Minimally invasive treatments for fibroids. ACOG Update 2014. http://www.acogupdate.com/?gp_page=p_onecourse&gp_skey=359 (Accessed on August 03, 2016).
- Rha SE, Byun JY, Jung SE, et al. CT and MRI of uterine sarcomas and their mimickers. AJR Am J Roentgenol 2003; 181:1369.
- Kitajima K, Murakami K, Kaji Y, Sugimura K. Spectrum of FDG PET/CT findings of uterine tumors. AJR Am J Roentgenol 2010; 195:737.
- MONTAGUE AC, SWARTZ DP, WOODRUFF JD. SARCOMA ARISING IN A LEIOMYOMA OF THE UTERUS: FACTORS INFLUENCING PROGNOSIS. Am J Obstet Gynecol 1965; 92:421.
- Baird DD, Garrett TA, Laughlin SK, et al. Short-term change in growth of uterine leiomyoma: tumor growth spurts. Fertil Steril 2011; 95:242.
- DeWaay DJ, Syrop CH, Nygaard IE, et al. Natural history of uterine polyps and leiomyomata. Obstet Gynecol 2002; 100:3.
- Peddada SD, Laughlin SK, Miner K, et al. Growth of uterine leiomyomata among premenopausal black and white women. Proc Natl Acad Sci U S A 2008; 105:19887.
- Kawamura N, Ito F, Ichimura T, et al. Transient rapid growth of uterine leiomyoma in a postmenopausal woman. Oncol Rep 1999; 6:1289.
- Jones MW, Norris HJ. Clinicopathologic study of 28 uterine leiomyosarcomas with metastasis. Int J Gynecol Pathol 1995; 14:243.
- Oduyebo T, Rau-Hain A, Meserve E, et al. The challenge of preoperative diagnosis of leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (abstract). Connective Tissue Oncology Society 18th annual meeting, October 2013.
- West S, Ruiz R, Parker WH. Abdominal myomectomy in women with very large uterine size. Fertil Steril 2006; 85:36.
- Sagae S, Yamashita K, Ishioka S, et al. Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma in Hokkaido, Japan. Oncology 2004; 67:33.
- Jin Y, Pan L, Wang X, et al. Clinical characteristics of endometrial stromal sarcoma from an academic medical hospital in China. Int J Gynecol Cancer 2010; 20:1535.
- Hinchcliff EM, Esselen KM, Watkins JC, et al. The Role of Endometrial Biopsy in the Preoperative Detection of Uterine Leiomyosarcoma. J Minim Invasive Gynecol 2016; 23:567.
- Bansal N, Herzog TJ, Burke W, et al. The utility of preoperative endometrial sampling for the detection of uterine sarcomas. Gynecol Oncol 2008; 110:43.
- Brölmann H, Tanos V, Grimbizis G, et al. Options on fibroid morcellation: a literature review. Gynecol Surg 2015; 12:3.
- Schwartz PE, Kelly MG. Malignant transformation of myomas: myth or reality? Obstet Gynecol Clin North Am 2006; 33:183.
- Quade BJ. Pathology, cytogenetics and molecular biology of uterine leiomyomas and other smooth muscle lesions. Curr Opin Obstet Gynecol 1995; 7:35.
- Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol 1994; 18:535.
- Tulandi T, Ferenczy A. Biopsy of uterine leiomyomata and frozen sections before laparoscopic morcellation. J Minim Invasive Gynecol 2014; 21:963.
- Quade BJ, Wang TY, Sornberger K, et al. Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling. Genes Chromosomes Cancer 2004; 40:97.
- Milad MP, Milad EA. Laparoscopic morcellator-related complications. J Minim Invasive Gynecol 2014; 21:486.
- Morice P, Rodriguez A, Rey A, et al. Prognostic value of initial surgical procedure for patients with uterine sarcoma: analysis of 123 patients. Eur J Gynaecol Oncol 2003; 24:237.
- Perri T, Korach J, Sadetzki S, et al. Uterine leiomyosarcoma: does the primary surgical procedure matter? Int J Gynecol Cancer 2009; 19:257.
- George S, Barysauskas C, Serrano C, et al. Retrospective cohort study evaluating the impact of intraperitoneal morcellation on outcomes of localized uterine leiomyosarcoma. Cancer 2014; 120:3154.
- Carta G, Palermo P, Di Ramio R, et al. Leiomyosarcoma after hysteroscopic myomectomy: a case report. Eur J Gynaecol Oncol 2012; 33:656.
- Einstein MH, Barakat RR, Chi DS, et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int J Gynecol Cancer 2008; 18:1065.
- Toubia T, Moulder JK, Schiff LD, et al. Peritoneal Washings After Power Morcellation in Laparoscopic Myomectomy: A Pilot Study. J Minim Invasive Gynecol 2016; 23:578.
- Gao Z, Li L, Meng Y. A Retrospective Analysis of the Impact of Myomectomy on Survival in Uterine Sarcoma. PLoS One 2016; 11:e0148050.
- Maresh MJ, Metcalfe MA, McPherson K, et al. The VALUE national hysterectomy study: description of the patients and their surgery. BJOG 2002; 109:302.
- Garry R, Fountain J, Mason S, et al. The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy. BMJ 2004; 328:129.
- American College of Obstetricians and Gynecologists. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol 2008; 112:387.
- Benedetti MD, Maraganore DM, Bower JH, et al. Hysterectomy, menopause, and estrogen use preceding Parkinson's disease: an exploratory case-control study. Mov Disord 2001; 16:830.
- Phung TK, Waltoft BL, Laursen TM, et al. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Dement Geriatr Cogn Disord 2010; 30:43.
- Rocca WA, Grossardt BR, Shuster LT, Stewart EA. Hysterectomy, oophorectomy, estrogen, and the risk of dementia. Neurodegener Dis 2012; 10:175.
- Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer 2008; 112:820.
- Hodge JC, Morton CC. Genetic heterogeneity among uterine leiomyomata: insights into malignant progression. Hum Mol Genet 2007; 16 Spec No 1:R7.
- Robboy SJ, Bentley RC, Butnor K, Anderson MC. Pathology and pathophysiology of uterine smooth-muscle tumors. Environ Health Perspect 2000; 108 Suppl 5:779.
- Giuntoli RL 2nd, Gostout BS, DiMarco CS, et al. Diagnostic criteria for uterine smooth muscle tumors: leiomyoma variants associated with malignant behavior. J Reprod Med 2007; 52:1001.
- Christacos NC, Quade BJ, Dal Cin P, Morton CC. Uterine leiomyomata with deletions of Ip represent a distinct cytogenetic subgroup associated with unusual histologic features. Genes Chromosomes Cancer 2006; 45:304.
- Taran FA, Weaver AL, Gostout BS, Stewart EA. Understanding cellular leiomyomas: a case-control study. Am J Obstet Gynecol 2010; 203:109.e1.
- Hodge JC, Pearce KE, Clayton AC, et al. Uterine cellular leiomyomata with chromosome 1p deletions represent a distinct entity. Am J Obstet Gynecol 2014; 210:572.e1.