Disclosures: Elizabeth A Stewart, MD Grant/Research/Clinical Trial Support: InSightec [Fibroids (Focused ultrasound device)]. Consultant/Advisory Boards: AbbVie [Fibroids (Leuprolide acetate)]; Bayer [Fibroids]; Astellas [Fibroids]; Glaxo Smith Kline [Adenomyosis]; Gynesonics [Fibroids (Intrauterine RF device)]; Viteava [Fibroids]. Robert L Barbieri, MD Nothing to disclose. Barbara Goff, MD Nothing to disclose. Tommaso Falcone, MD, FRCSC, FACOG Nothing to disclose. Sandy J Falk, MD, FACOG Nothing to disclose.
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 tumor 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 per 100,000 in the United States population) with a poor prognosis .
Clinicians who are evaluating a woman with presumed leiomyomas are presented with the clinical challenge of deciding which rare patients may have sarcoma. While there are differences in the populations of the two disorders, there is some overlap. There are several histologic types of uterine sarcoma. The main type of sarcoma that may resemble a leiomyoma is leiomyosarcoma, which presents as a myometrial mass. In contrast, endometrial stromal sarcoma presents as an endometrial mass. However, this could potentially have a similar appearance to a submucosal leiomyoma.
Historically, hysterectomy was the mainstay of treatment for women with a uterine mass, and uterine sarcoma, if present, was identified by pathologic analysis. In current practice, women with presumed benign leiomyomas are treated with a variety of medical and conservative surgical or interventional procedures. Non-excisional therapies for fibroid-related symptoms (eg, hormonal contraception, endometrial ablation, interventional radiology procedures) do not produce specimens for pathologic examination. Thus, the diagnosis of malignant disease 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 malignant cells. Equally important priorities, however, are to avoid unnecessary surgery for the purpose of excluding the rare sarcoma and offering the option of minimally invasive approaches in low-risk patients.
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 leiomyoma variants are discussed separately. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)" and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis" and "Treatment and prognosis of uterine leiomyosarcoma" and "Variants of uterine leiomyomas (fibroids)" and "Classification and treatment of endometrial stromal tumors".)
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 both benign and malignant conditions:
●Uterine adenomyoma or diffuse adenomyosis
●Uterine carcinosarcoma (considered an epithelial neoplasm)
●Metastatic disease (typically from another reproductive tract primary)
The differential diagnosis of an enlarged uterus is discussed in detail separately. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Differential diagnosis'.)
PREVALENCE OF SARCOMA AFTER SURGERY FOR PRESUMED LEIOMYOMAS — Uterine sarcoma is rare (3 to 7 per 100,000 United States women, as noted above) . The rate of sarcoma in women with a symptomatic uterine mass 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. The available studies, which document the prevalence of sarcomas in women with myometrial mass(es), are retrospective case series. Additional limitations of these studies include: many were conducted at referral centers, and so may include 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; and 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 0.1 (1 in 1000) to 0.28 percent (1 in 352), depending upon which studies are included or excluded [5-20]. The majority of cases reported were leiomyosarcoma, but these studies included a few cases of endometrial stromal sarcoma. The prevalence of leiomyosarcoma is therefore likely slightly higher.
The largest study that evaluated unexpected malignancy 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, found that morcellation was performed in 36,470 (15.7 percent) . Among the women who had morcellation, there were 99 cases of uterine cancer (0.27 percent; 1 in 370); 39 uterine neoplasms of uncertain malignant potential; 368 cases of endometrial hyperplasia (most cases were without atypia ); and 26 other gynecologic malignancies. The prevalence of malignancy was 0.34 percent and of all neoplastic conditions was 1.5 percent, although the clinical significance of endometrial hyperplasia without atypia is uncertain. Malignant disease 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 cancer 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. (See 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' below.)
A large 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 malignancy; among the other women, six were diagnosed with leiomyosarcoma on endometrial biopsy prior to surgery and 14 had findings suspicious for malignancy 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 malignancy 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 malignancy was 2.7 percent, including: ovarian, peritoneal, and fallopian tube cancer (1.1 percent); endometrial cancer (1.0 percent); uterine sarcoma (0.2 percent); cervical cancer (0.2 percent); and metastatic cancer (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 without 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 (n = 14), nine had a diagnosis of abnormal uterine bleeding (and thus would have required further evaluation). Limitations of this study include that it did not provide data regarding risk factors for uterine malignancy (eg, Reed syndrome in young patients ), preoperative evaluation, or the surgical approach or technique (eg, laparoscopy, morcellation). It also did not specify whether the malignancy 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.
Regarding myomectomy, data from a national United States hospital database of 41,777 women undergoing myomectomy, including 3220 women who underwent myomectomy with power morcellation, reported that 0.43 percent had a pathologic finding (cancer, tumors 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 power morcellation should not be used in peri- and postmenopausal women with a uterine tumor.
CLINICAL CHARACTERISTICS — 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 manifestations of benign leiomyomas and uterine sarcomas are often indistinguishable.
Risk factors — Uterine sarcoma is rare and risk factors are not well defined for 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 fibroids is two- to three-fold greater in black women than in white women. The cumulative incidence of fibroids 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 "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Prevalence'.)
Similarly, black women have an approximately two-fold higher incidence of leiomyosarcomas (but not other types of uterine sarcoma) and carcinosarcoma than white women . (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Race'.)
Increasing age and postmenopausal status — Benign leiomyomas 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. Fibroids 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 fibroids. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Prevalence' and "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", 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 . (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Epidemiology'.)
Thus, particularly 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, stopping postmenopausal estrogen therapy is also an option to see if regression occurs. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Women on hormone therapy'.)
The available evidence supports an increased risk of undetected malignancy in women 50 years or older who undergo morcellation of uterine tissue . (See 'Prevalence of sarcoma after surgery for presumed 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 per 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 [28,29]. (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 (HLRCC) 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 "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Prevalence' and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Other risk factors'.)
Clinical manifestations — 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 [26,30-32]. Some women with sarcoma present with a foul-smelling vaginal discharge, but this is not a reliable indicator of malignancy since vaginal discharge is a common gynecologic symptom. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", section on 'Clinical manifestations' and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Clinical presentation'.)
Clinical manifestations associated with metastatic disease may be found in women with sarcoma, but not with ordinary leiomyomas. Uterine sarcomas spread via intraabdominal, lymphatic, or hematogenous routes. Hematogenous spread is most often to the lungs. Of note, some 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 tumors", section on 'Evaluation of suspected disease'.)
Failure to respond to treatment — Failure to respond to medical treatment (gonadotropin-releasing hormone [GnRH] agonist treatment) or non-excisional procedures such as uterine artery embolization for leiomyomas has preceded a diagnosis of malignancy in multiple reports [33-39]. However, such treatment failures are not definitive evidence of malignancy.
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 surgery (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 — The diagnosis of uterine sarcoma is based upon histologic examination. Uterine sarcomas are most commonly diagnosed following myomectomy or hysterectomy for presumed leiomyomas.
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. Unfortunately, however, there are no examination findings that distinguish a leiomyoma from a uterine sarcoma.
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 often have central necrosis.
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. 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 [43,44]. 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 — The common teaching has 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 [48-51]. 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 "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas (fibroids)", 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 (1 uterine sarcoma; 0.27 percent) and in the 961 without rapid uterine growth (2 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 sarcoma . Thus, the great majority of premenopausal women with a rapidly enlarging uterus or uterine mass do not have a sarcoma. Moreover, research on normal leiomyomas show that growth of up to 138 percent can occur within six-months .
In contrast, 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 [26,30,52,53]. 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 [26,54]. As a result, these features are not useful in identifying malignancy.
Biopsy — Endometrial sampling can detect some uterine sarcomas. Preoperative imaging-guided biopsy is generally not performed, but intraoperative biopsy is indicated if there are suspicious findings during surgery.
Endometrial sampling — Endometrial sampling yields a preoperative diagnosis in some women with uterine sarcoma [55,56]. There are few data regarding use of endometrial sampling in women with sarcoma, and only two small studies have reported the sensitivity of preoperative endometrial sampling for a diagnosis of leiomyosarcoma. In one study, among women with leiomyosarcoma, three of eight (38 percent]) who underwent preoperative sampling had a correct diagnosis . In another study, the sensitivity for a diagnosis of leiomyosarcoma was four of six (67 percent), but two additional women with leiomyosarcoma had preoperative pathology results that reported malignant disease, but an incorrect histologic diagnosis (one endometrial carcinoma, one other sarcoma ). Thus, these women would have been managed surgically as appropriate for a malignancy. In addition, in the same study, the sensitivity for a diagnosis of endometrial stromal sarcoma was two of six women (33 percent), and the pathology results in the remaining four women were negative. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis", section on 'Biopsy'.)
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 sampling in women in whom sarcoma is suspected or for whom the planned procedure includes intraperitoneal morcellation, which would disrupt the specimen and potentially disseminate malignant tissue. (See 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' below.)
Other biopsy techniques — Infrequently, a uterine sarcoma will prolapse through the cervix and can be biopsied .
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.
Intraoperative evaluation — During myomectomy, some tumor characteristics may raise suspicion of malignancy. Frozen section analysis cannot definitively diagnose or exclude uterine sarcoma.
Gross characteristics of the mass — During excisional surgery, uterine sarcomas may appear or feel different than leiomyomas. Potential features of sarcomas compared with leiomyomas include (picture 1) [58-60]:
●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 [GnRH] 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 [8,30,61]. 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 pathologic evaluation — Three criteria are important to the diagnosis of uterine sarcomas: mitotic index, cellular atypia, and geographic areas of coagulative necrosis separated from viable tumor [60,62]. The more features exhibited by the lesion, the more likely it is to have clinically aggressive behavior [60,62]. There are a number of pathologic entities in which lesions display some, but not all, of the facets of malignancy. (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 morcellation, myomectomy, or supracervical hysterectomy worsen prognosis? — The risk of techniques such as myomectomy, intraperitoneal morcellation (cutting tissue into pieces to remove through a small incision), 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 disseminated tissue implants that require further treatment . Another concern is that the morcellated specimen is more difficult for pathologists to evaluate. (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 (power morcellation, scalpel morcellation, supracervical hysterectomy, abdominal or hysteroscopic myomectomy) is uncertain [16,64-67].
There is no reliable method to distinguish uterine sarcoma from benign leiomyomas preoperatively, as discussed in detail above. Among women planning surgery for one or more uterine masses that are presumed to be benign leiomyomas, the prevalence of uterine sarcoma is less than 1 in 323. (See 'Prevalence of sarcoma after surgery for presumed leiomyomas' above.)
In addition to uterine sarcoma, there is concern about morcellation of uterine smooth muscle tumors of uncertain malignant potential or other uterine malignant or premalignant conditions (endometrial carcinoma, endometrial hyperplasia, carcinosarcoma). Endometrial carcinoma or hyperplasia is typically diagnosed preoperatively, since endometrial sampling is a simple and effective diagnostic method and should be performed in all women preoperatively if indicated (table 1). However, unsuspected endometrial carcinoma is occasionally diagnosed postoperatively, particularly in asymptomatic women and in those who undergo hysterectomy for indications other than abnormal uterine bleeding (eg, pelvic organ prolapse) [68-71]. (See "Endometrial sampling procedures".)
Comparative studies have reported that morcellation is associated with a worse prognosis for women with uterine sarcoma [16,64-66,72,73]. However, there are few data and the available studies often include both scalpel and power morcellation with hysterectomy or for myomectomy. A meta-analysis of four observational studies in women with uterine sarcoma found that morcellation (scalpel or power methods) compared with no morcellation was associated with a significantly higher recurrence rate (61 versus 39 percent; odds ratio [OR] 3.16, 95% CI 1.38-7.26) and mortality rate (48 versus 29 percent; OR 2.42, 95% CI 1.19-4.92) . The intraabdominal recurrence rate was significantly higher in women who had undergone morcellation compared with other patients, while the extraabdominal recurrence rate showed a trend toward being higher in women who had not undergone morcellation. One retrospective study included in the analysis of women with uterine sarcoma confined to the uterus at presentation (19 had intraperitoneal scalpel or power morcellation; 38 had total abdominal hysterectomy) found that morcellation was associated with a significant decrease in the median time to recurrence (10.8 versus 39.6 months) .
Regarding supracervical hysterectomy, a small study of women with endometrial carcinoma or uterine sarcoma found that 12 patients who underwent supracervical hysterectomy were not upstaged, while 2 of 5 patients who underwent power morcellation (along with myomectomy or hysterectomy) were upstaged from stage I to stage III .
Counseling of women with presumed uterine fibroids includes discussion of the risks and benefits of available treatment options and appropriate assessment for endometrial carcinoma and uterine sarcoma, including evaluation for current disease and risk factors. In appropriately counseled patients, patient preference should be a major determining factor regarding surgical approach. Because a preoperative diagnosis of sarcoma is uncommon, morcellation of a malignant tumor may occur even in low-risk women. (See 'Risk factors' above.)
Surgical techniques that disrupt the uterine specimen (scalpel or power morcellation, supracervical hysterectomy) should NOT be performed in women with known or suspected uterine or other gynecologic cancer. We recommend NOT using power morcellation of uterine tissue for women who have significant risk factors for uterine sarcoma (eg, postmenopausal status, history of ≥2 years of tamoxifen therapy, history of pelvic irradiation, history of childhood retinoblastoma, or personal history of hereditary leiomyomatosis and renal cell carcinoma [HLRCC] syndrome).
For premenopausal women with uterine fibroids and no significant uterine sarcoma risk factors, for those who desire uterine preservation and are candidates for laparoscopic myomectomy, we offer patients myomectomy with morcellation rather than myomectomy via laparotomy. For those who desire laparoscopic hysterectomy and in whom intact removal of the specimen through the vagina is not possible, we offer laparoscopic hysterectomy with morcellation rather than laparotomy. Based upon appropriate counseling regarding risks and benefits of morcellation versus laparotomy, the patient can then make an informed choice regarding the surgical approach.
If a surgical option using power morcellation is elected, counselling should include the risk of dissemination of malignant cells, if a malignancy is incidentally detected [75-79]. In cases in which the postoperative pathology shows malignancy, the patient should be referred to a gynecologic oncologist for further evaluation and treatment as soon as possible.
An area of uncertainly regarding morcellation is how to manage perimenopausal women; the US Food and Drug Administration (FDA) advises against power morcellation in perimenopausal women. The perimenopausal transition can occur over approximately eight years, extending from the time of regular menstrual cycles to the final menstrual period (which is not considered final until one year has passed). However, there is no evidence that perimenopausal women are at an increased risk of uterine sarcoma. The principal basis of the increased risk in menopausal women is that uterine fibroids are unlikely to increase in size or become symptomatic in a hypoestrogenic state, which is not the case during the menopausal transition, during which hormone levels can fluctuate significantly. (See 'Policy statements' below.)
In addition, the FDA advises against power morcellation in women who are candidates for en bloc tissue removal. This mainly applies to hysterectomy, and en bloc tissue removal is preferable whenever possible. This is often possible in less invasive procedures, including vaginal or laparoscopic hysterectomy. However, for women who have no significant risk factors for uterine sarcoma, use of laparotomy rather than a less invasive approach, solely to avoid morcellation, may expose women to higher risks of morbidity and mortality and certainly to a longer recovery period that may affect quality of life . For women who desire uterine preservation, myomectomy using any surgical approach generally involves a great deal of disruption of the specimen(s). There are no data regarding whether laparoscopic myomectomy with power morcellation or open myomectomy result in a differential risk of tissue dissemination.
In response to concerns about dissemination of malignant tissue with power morcellation, some institutions in the United States have suspended use of power morcellation in women with uterine masses. One device manufacturer has suspended sales of a power morcellator and recalled all morcellator devices [81,82].
Use of morcellation in other surgical specialties is discussed separately. (See "Instruments and devices used in laparoscopic surgery", section on 'Morcellators'.)
Policy statements — The risk of a dissemination of malignant cells in women with an incidental finding of malignancy associated with power morcellation of uterine tissue has been the focus of review and statements by the US FDA, the American College of Obstetricians and Gynecologists, AAGL, and the Society of Gynecologic Oncology (SGO) [5,18,75,78,83]. All of these statements emphasize the importance of several key preoperative steps when morcellation is planned, including: appropriate evaluation for uterine and cervical cancer, assessment for uterine sarcoma risk factors, and informed consent regarding the risk of tumor dissemination. In addition, all organizations have acknowledged the need to gather more data regarding the risks of morcellation.
Government agencies — In July 2014 the FDA convened a public meeting of the Obstetrics and Gynecological Medical Device Advisory Committee. Based upon this meeting and a systematic review of the use of power morcellation , in November 2014 the FDA published an updated safety communication with the following recommendations :
●Laparoscopic power morcellators are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal or are candidates for en bloc tissue removal: for example, through the vagina or mini-laparotomy incision. (Note: These groups of women represent the majority of women with fibroids who undergo hysterectomy and myomectomy).
●Laparoscopic power morcellators are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.
●Be aware of the following new boxed warning recommended by the US FDA: The US FDA warns that uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.
●Carefully consider all the available treatment options for women with uterine fibroids.
●Thoroughly discuss the benefits and risks of all treatments with patients. Be certain to inform the small group of patients for whom laparoscopic power morcellation may be an acceptable therapeutic option that their fibroid(s) may contain unexpected cancerous tissue and that laparoscopic power morcellation may spread the cancer, significantly worsening their prognosis. This population might include some younger women who want to maintain their fertility or women not yet peri-menopausal who wish to keep their uterus after being informed of the risks.
In May 2014, Health Canada issued a statement to hospital leadership regarding use of electric morcellators during laparoscopic hysterectomy and myomectomy with the following recommendations :
●Recognize the prevalence of unsuspected uterine sarcoma in patients under consideration for hysterectomy or myomectomy for the treatment of uterine fibroids.
●Consider the treatment alternatives for women with symptomatic uterine fibroids and review these options with each prospective surgical patient. Apart from a laparoscopic approach, alternative surgical procedures exist that do not require electric morcellation. Also, some surgeons and centers may recommend closed morcellation in a bag as a way to reduce the risk of inadvertent spread of uterine tissue.
●Be aware and inform patients that laparoscopic electric morcellation of unsuspected uterine sarcoma during hysterectomy or myomectomy may disseminate the disease and negatively impact prognosis.
Professional societies — The ACOG statement addresses both the risks and benefits of morcellation; the following are excerpts :
●We continue to believe that power morcellation has a role in gynecologic surgery. Power morcellation can make it possible for some women to undergo less-invasive laparoscopic hysterectomy or myomectomy, sparing them the longer recovery time and higher mortality rates associated with a total abdominal procedure.
●Although the worsening of an occult malignancy as a result of power morcellation is, of course, tragic, we believe that an approach that combines deliberate patient selection criteria with robust informed consent will help protect women from a negative outcome, while maintaining access to morcellation for women who would benefit from it.
The AAGL statement regarding the FDA safety communication includes the following :
●The following information needs to be clarified: a specific definition of peri-menopausal women; the role of power morcellation in the large group of reproductive-aged women who undergo myomectomy for fertility-sparing surgery; use of power morcellation in patients with non-fibroid uteri who may have refractory uterine bleeding, prolapse or adenomyosis; guidance regarding the use of containment bags; and guidance regarding the role of non-power morcellation (use of a manual cold knife scalpel in vaginal or mini-laparotomy tissue extraction).
●Abandoning power morcellation technology for many patients undergoing minimally invasive myomectomy, supracervical hysterectomy, or hysterectomy for a large uterus will be a setback in the care of patients with gynecologic conditions. With meticulous adherence to preoperative patient selection guidelines and informed consent, the AAGL believes appropriately performed power morcellation outweighs the risk of laparotomy in low-risk patients and is an option to be carefully considered by patients and their gynecologists.
Alternatives or modifications to morcellation — Use of power morcellation is an ongoing area of investigation, and further practice modifications may continue to evolve. Alternative or modified surgical techniques include:
●Intact removal of a specimen using minimally invasive approaches that do not require power morcellation – These include removing the specimen intact via mini-laparotomy or colpotomy (following vaginal hysterectomy or total laparoscopic hysterectomy) .
●Extracorporeal morcellation, in which a specimen is brought to a mini-laparotomy incision or colpotomy and morcellated via the incision – Some experts advise use of a circumferential wound retractor to facilitate this technique [79,86,87]. This may require containing the specimen in an intracorporeal specimen bag to avoid dissemination of tissue.
●Intracorporeal morcellation within a specimen bag – Some surgeons contain a uterine specimen in a laparoscopic bag and morcellate in the bag to attempt to avoid tumor dissemination [88-97]. The safety and efficacy of use of a laparoscopic bag require further study. One concern regarding this approach is the limited ability to visualize the tissue being morcellated and surrounding structures to avoid damage if the bag is penetrated by the morcellator blade; such complications have been reported . In addition, if the bag is disrupted by the morcellator blade or by the insertion of ports or instruments, tissue may be disseminated. Some institutions allow use of these methods only as part of research protocols. Use of a laparoscopic bag with morcellation is also used by other surgical specialties. (See "Instruments and devices used in laparoscopic surgery", section on 'Tissue bags'.)
●Laparotomy – This is an option, but is associated with a larger incision, more postoperative pain, a longer recovery period, and potentially more complications than minimally invasive approaches .
Should hysterectomy be performed to exclude uterine sarcoma? — For most women with presumed uterine leiomyomas, whether asymptomatic or symptomatic, we recommend not performing hysterectomy for the sole purpose of excluding malignancy. 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 [6-15]. 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 [98,99]. This recommendation is in agreement with ACOG, 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 is a definitive procedure, but the disadvantages are loss of fertility, risk of surgical complications, the time needed for recovery, and risk of long-term morbidity, especially if the ovaries are removed at the time of hysterectomy [101-103]. 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 malignancy. 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 malignancy 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 malignancy . 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. 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 metastatic disease. One note of caution is that women with apparent intraabdominal metastases may have a primary malignancy 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 intraabdominal 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. Genetic evidence has been inconsistent over the years regarding whether sarcomas arise de novo or whether there is karyotypic evolution from leiomyomas to sarcomas, so called sarcomatous degeneration. 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 tumors . 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 [107-110]. 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'.)
SUMMARY AND RECOMMENDATIONS
●Benign uterine leiomyomas (fibroids) are the most common pelvic tumor in women (lifetime risk 70 to 80 percent). Uterine sarcoma is rare (3 to 7 per 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 'Prevalence of sarcoma after surgery for presumed 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 'Clinical manifestations' 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 an 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 who have a uterine mass and who have risk factors for uterine sarcoma and/or other findings that raise suspicion of uterine sarcoma. (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) 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.)
●Counseling of women with presumed uterine fibroids includes discussion of all available treatment options, including the risks and benefits of different surgical approaches. Appropriate assessment for endometrial carcinoma and uterine sarcoma should be performed, including evaluation for current disease and risk factors. (See 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' above.)
●Surgical techniques that disrupt the uterine specimen (scalpel or power morcellation, supracervical hysterectomy) should NOT be performed in women with known or suspected uterine or other gynecologic cancer. We recommend NOT using power morcellation of uterine tissue for women who have significant risk factors for uterine sarcoma (eg, postmenopausal status, history of ≥2 years of tamoxifen therapy, history of pelvic irradiation, history of childhood retinoblastoma, or personal history of hereditary leiomyomatosis and renal cell carcinoma [HLRCC] syndrome) (Grade 1C). (See 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' above.)
●For premenopausal women with uterine fibroids and no significant uterine sarcoma risk factors, based upon appropriate counseling regarding risks and benefits of morcellation versus laparotomy, the patient can then make an informed choice regarding the surgical approach (see 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' above):
•For those who desire uterine preservation and are candidates for laparoscopic myomectomy, in our practice, we offer patients myomectomy with morcellation rather than myomectomy via laparotomy.
•For those who desire laparoscopic hysterectomy and in whom intact removal of the specimen through the vagina is not possible, in our practice, we offer laparoscopic hysterectomy with morcellation.
●If a surgical option using power morcellation is elected, counselling should include the risk of dissemination of malignant cells, if a malignancy is incidentally detected. (See 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?' above.)
●For most women with presumed uterine leiomyomas, whether asymptomatic or symptomatic, we recommend NOT performing hysterectomy for the sole purpose of excluding malignancy (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.)
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