Uterine Leiomyoma and Leiomyosarcoma

Uterine leiomyomas (or uterine fibroids) are benign tumors arising from smooth muscle cells in the uterine myometrium. Leiomyosarcomas, however, are malignant tumors, arising de novo (not from fibroids). With a lifetime risk of > 70% for both African American and Caucasian women, fibroids are common. Conversely, leiomyosarcomas are rare. Leiomyosarcomas may present similarly to uterine fibroids making preoperative diagnosis challenging. Both conditions present with abnormal bleeding, pelvic pain, and/or bulk symptoms. A fibroid is identified as a hypoechoic, well-circumscribed, round mass on pelvic ultrasound. A leiomyosarcoma is usually diagnosed on a postoperative specimen. Depending on patient symptoms and preference, treatment for leiomyoma may include surgical resection or medical options to reduce bleeding and/or bulk. Management of leiomyosarcoma, which carries a poor prognosis, may include adjuvant chemotherapy based on stage.

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Leiomyomas are benign, smooth muscle tumors arising from the uterine myometrium, whereas leiomyosarcomas are aggressive, malignant tumors of the myometrium.


  • The most common pelvic tumor in women
  • Occur in reproductive-age women:
    • Prevalence ↑ with age during the reproductive years
    • May be diagnosed (but do not form) after menopause
  • Estimated lifetime risks:
    • African American women: 80%
    • Caucasian women: 70%


  • Very rare
  • < 10% of uterine corpus cancers
  • Incidence: 
    • 3–7 per 100,000
    • 1 per 500 in patients undergoing surgery for a myometrial mass
  • Peak incidence: 40–60 years old



  • Monoclonal tumor of the uterine myometrium
  • Arises from myocytes 
  • Contains a considerable amount of collagen
  • Round, firm, rubbery, well-circumscribed, white-tan mass(es)
  • Responsive to estrogen:
    • ↑ In pregnancy
    • ↓ After menopause

Predisposing factors:

  • Race: African American > Caucasian women
  • Reproductive factors:
    • Nulliparity (pregnancy is a progesterone dominant state → a reprieve from chronic estrogen exposure that can stimulate leiomyomas)
    • Early menarche
    • Late menopause
  • Obesity
  • Family history of fibroids


  • Intramural:
    • Located within the myometrial wall
    • May extend into the cavity/subserosa or be completely contained within the wall
    • Most common overall
  • Submucosal:
    • Located just under the endometrium
    • Distorts the endometrial cavity
    • Most often responsible for abnormal bleeding and fertility challenges
    • May be pedunculated growing into the endometrial cavity on a stalk
  • Subserosal:
    • Located just beneath the serosa
    • Most likely to cause bulk symptoms
  • Pedunculated:
    • Growing off of the uterine corpus on a stalk 
    • Can torse and cause acute pain
  • Cervical:
    • Originating within the cervix
    • Rare
Uterine fibroids

Uterine fibroids (location):
Subserosal fibroid (beneath the serosa), submucosal fibroid (under the endometrium), intramural fibroid (in the myometrial wall), pedunculated fibroid (growing off the uterine corpus on a stalk)

Image by Lecturio.


  • Malignant tumors of the uterine corpus
  • Arise de novo (not from leiomyomas)


  • Bulky, fleshy mass invading the uterine wall
  • Polypoid mass projecting into the endometrial cavity

Differentiated from leiomyomas by the degree of:

  • Nuclear atypia
  • Mitotic activity

Predisposing factors:

  • ↑ Risk in African American women
  • Older age and postmenopausal status
  • Tamoxifen use
  • History of pelvic radiation

Clinical Presentation

Presentations of leiomyoma and leiomyosarcoma can be clinically indistinguishable.

Both leiomyoma and leiomyosarcoma may be asymptomatic.

Menstrual/bleeding symptoms

  • Heavy menstrual bleeding
  • Prolonged menstrual bleeding
  • Intermenstrual or postcoital bleeding (especially with fibroids prolapsed through the cervix)
  • Postmenopausal bleeding

Pain symptoms

  • Dysmenorrhea
  • Pelvic pain
  • Dyspareunia (painful intercourse)
  • Acute pain from:
    • Leiomyoma degeneration
    • Torsion of pedunculated lesions

Bulk-related symptoms

  • Pelvic pressure
  • ↑ Urinary frequency
  • Constipation (with rectal compression)
  • Pelvic mass

Reproductive dysfunction

  • Infertility (caused by distortion of the endometrial cavity)
  • Recurrent pregnancy loss
  • Other obstetric complications


Workup for leiomyomas and leiomyosarcomas are the same, but there are no tests or findings with high positive predictive value for sarcomas.

Pelvic exam

  • Asymmetrically enlarged uterus with an irregular contour
  • Small fibroids will not enlarge the size of the uterus.

Imaging and endoscopy

  • Transvaginal ultrasound (1st step):
    • Sensitivity for detecting leiomyomas: 95%–100%
    • Hypoechoic, well-circumscribed, round mass
    • Calcifications → degenerating fibroid
    • Features concerning for leiomyosarcoma: mixed echogenicity, central necrosis, irregular vessel distribution
  • Saline infusion sonogram (follow-up test):
    • Sterile saline is injected into the endometrial cavity to distend it during vaginal sonography in order to evaluate intracavitary lesions.
    • Used in cases of suspected submucosal fibroids and infertility patients
  • Hysteroscopy: allows for evaluation and simultaneous treatment of intracavitary pathology, including submucosal fibroids
  • Pelvic MRI:
    • Rarely indicated (helps in planning surgeries)
    • Leiomyomas: dark, homogenous T2 images 
    • Leiomyosarcomas: ill-defined margins
  • Findings with high negative predictive value for sarcoma:
    • Typical leiomyoma appearance on MRI (dark, homogenous T2 images)
    • Absence of calcifications
Radiology of uterine fibroids

A 49-year-old woman with a history of menorrhagia:
A: Transabdominal ultrasound image showing a bulky uterus with 10 cm submucosal fibroid (between cursors)
B: Sagittal T2 weighted MRI in the same patient shows the submucosal fibroid (arrowhead) is heterogeneous, indicating degeneration. Also shown is a 2.5 cm cervical fibroid (arrow).

Image: “ Menorrhagia” by Department of Radiology, Norfolk & Norwich University Hospital, Colney Lane, Norwich, Norfolk, NR4 7UY, United Kingdom. License: CC BY 2.0

Definitive diagnosis requires histologic examination

  • Endometrial biopsy:
    • Unlikely to diagnose leiomyoma or leiomyosarcoma
    • Used to rule out other causes of abnormal bleeding
  • Intraoperative evaluation

Management and Prognosis

Medical management for leiomyomas

General management:

  • Treat pain: NSAIDs
  • Treat anemia: iron supplementation
  • Observation is an option if patients are asymptomatic.

To treat bleeding symptoms (1st-line medical management):

  • Hormonal:
    • Progestins: levonorgestrel-releasing intrauterine device (IUD)
    • Combined hormonal contraceptives (pills, patch, vaginal ring)
  • Nonhormonal: antifibrinolytics (tranexamic acid)

To treat bulk or pain symptoms (1st line) or bleeding symptoms (2nd line):

Gonadotropin-releasing hormone (GNRH) analogs:

  • Elagolix (GNRH antagonist)
  • Leuprolide (GNRH agonist)
  • Both agonists and antagonists completely suppress follicle-stimulating hormone (FSH) → ↓ estrogen → fibroids shrink
  • Limit therapy to 6–12 months to prevent osteoporosis.

Surgical management for leiomyomas

  • Hysteroscopic resection:
    • Only useful for submucosal leiomyomas
    • 1st-line treatment for submucosal fibroids associated with:
      • Heavy menstrual bleeding
      • Fertility challenges
  • Myomectomy:
    • Removal of leiomyomas from the uterus
    • Used in patients who wish to retain fertility with nonsubmucosal leiomyomas
  • Hysterectomy:
    • Removal of the entire uterus
    • Considered definitive treatment for leiomyomas
    • 1st line if leiomyosarcoma is suspected
  • Alternatives to surgical resection:
    • Uterine artery embolization
      • ↓ Blood supply to fibroids → necrosis
      • Beneficial for bleeding and bulk symptoms
      • Should not be used in patients desiring future fertility
    • Focused ultrasound surgery: high-intensity ultrasound induces necrosis

Management and prognosis of leiomyosarcomas

Leiomyosarcomas are usually only diagnosed following surgery for presumed fibroids. Management decisions are typically made after an initial procedure:

  • Total hysterectomy if not already performed
  • Adjuvant therapy depending on stage:
    • Chemotherapy
    • Radiation is still investigational


  • Generally poor
  • ↑ Risk of recurrence
  • 5-year, disease-specific survival: 66%

Differential Diagnosis

The differential diagnoses of uterine mass and/or pelvic pain include:

  • Pregnancy: may present as an enlarging uterine mass with increasing pelvic pressure, bulk symptoms, and bleeding abnormalities if there are obstetric complications (e.g., subchorionic hemorrhage). Diagnosis is made with a pregnancy test and confirmed via ultrasound. 
  • Endometriosis: the ectopic implantation of functional endometrium outside the uterine cavity, leading to potentially severe dysmenorrhea, inflammation, and fertility challenges. Ultrasound may show an endometrioma (ovarian cyst filled with endometrial tissue), but will not demonstrate a uterine mass. Treatment usually involves suppression of the endometrium with progestins, or, in more severe cases, GNRH analogs/laparoscopic treatment.
  • Adenomyosis: endometrial implants within the uterine myometrium, which lead to heavy, prolonged, and often painful menstrual bleeding similar to leiomyomas. The implants cause the uterus to become symmetrically enlarged, boggy, and globular. Discrete masses are not present, which distinguishes adenomyosis from leiomyomas on ultrasound. Management is similar to endometriosis. However, adenomyosis also commonly includes a hysterectomy for definitive treatment.
  • Endometrial polyps: arise from an overgrowth in the endometrial epithelium. Polyps are usually (though not always) benign and typically present with abnormal uterine bleeding (if symptomatic at all). Endometrial polyps are best seen with a saline-infusion sonogram and appear as a pedunculated intracavitary mass (compared to most submucosal fibroids, which are less likely to have a stalk). Treatment (and definitive diagnosis) is by hysteroscopic resection.
  • Other malignancies: other malignancies of the uterus or reproductive organs may also present with enlarged uterine mass and/or abnormal bleeding. The most important malignancies to consider include uterine carcinosarcoma, endometrial carcinoma, and metastases from other organs (especially the ovaries, fallopian tubes, cervix, and vagina). A leiomyoma is often easily differentiated from other malignancies on ultrasound. An endometrial biopsy and a pap smear are the best options to identify endometrial and cervical cancers, respectively.


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