Leiomyoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Shanshan Cen, M.D. [3]; Ammu Susheela, M.D. [4]

Synonyms and keywords: Uterine myoma; Fibroid; Fibroids, Uterine; Fibroid Tumor; Fibroid Uterus; Uterine fibromyoma

Overview

Uterine leiomyoma was first discovered by Hippocrates in 460-375 B.C and called it “uterine stone”. Uterine leiomyoma may be classified according to their location into 3 subtypes: submucosal, subserous, and intramural. The pathogenesis of leiomyoma is characterized by benign smooth muscle neoplasm. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus. Chromosome aberrations such as t(12;14)(q14-q15;q23–24), del(7)(q22q32), rearrangements involving 6p21, 10q, trisomy 12, and deletions of 1p3q has been associated with the development of leiomyoma. Uterine leiomyoma must be differentiated from other diseases that cause uterine mass, such as: uterine adenomyoma, pregnancy, hematometra, uterine sarcoma, uterine carcinosarcoma, and metastasis. Leiomyoma is more commonly observed among patients aged 40 years and older. Common risk factors in the development of uterine leiomyoma include African-American race, early menarche, prenatal exposure to diethylstilbestrol, having one or more pregnancies extending beyond 20 weeks, obesity, significant consumption of beef and other reds meats, hypertension, family history, and alcohol consumption. Physical examination may be remarkable for enlarged, mobile uterus with an irregular contour on bimanual pelvic examination. The mainstay of therapy for uterine leiomyoma is oral contraceptive pills, either combination pills or progestin-only, Gonadotropin-releasing hormone analogs. Surgery is also part of mainstay therapy for uterine leiomyoma.

Historical Perspective

• Uterine leiomyoma was first discovered by Hippocrates, an ancient Greek physician, in 460-375 B.C and called it “uterine stone”.
• In the second century AD, Galen described the lesion as "scleromas".
• In 1860 and 1863, Rokitansky and Klob coined the term fibroid.
• In 1854, Virchow, a German pathologist, demonstrated that those tumors originated from the uterine smooth muscle.
• In 1809, the first laparotomy was conducted by Ephraim McDowell to treat leiomyoma in Danville, USA.

Classification

• Leiomyoma may be classified according to the International Federation of Gynecology and Obstetrics (FIGO) classification system, based on their location in the uterus, into 8 subtypes:
  • Intramural myomas
    • FIGO types 3, 4, and 5
    • Located within the uterine wall
  • Submucosal myomas
    • Derived from myometrial cells below the endometrium and may protrude into the uterine cavity
    • May be subclassified according to this protrusion:
      • Type 0: pedunculated intracavitary
      • Type 1: < 50% intramural
      • Type 2: ≥ 50% itramural
  • Subserosal myomas
  • Cervical myomas

Pathophysiology

• The pathogenesis of leiomyoma is characterized by benign smooth muscle neoplasm. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus.
• The chromosome aberrations such as t(12;14)(q14-q15;q23–24), del(7)(q22q32), rearrangements involving 6p21, 10q, trisomy 12, and deletions of 1p3q have been associated with the development of leiomyoma.
• On gross pathology, round, well circumscribed (but not encapsulated), solid nodules that are white or tan, and whorled are characteristic findings of leiomyoma .
• On microscopic histopathological analysis, elongated, spindle-shaped cells with a cigar-shaped nucleus are characteristic findings of leiomyoma.

Uterine Leiomyomata

Uterine fibroids are leiomyomata of the uterine smooth muscle. As with other leiomyomata, they are benign, but may lead to excessive menstrual bleeding (menorrhagia), often cause anemia and may lead to infertility. Enucleation is removal of fibroids without removing the uterus (hysterectomy), which is also commonly performed. Laser surgery (called myolysis) is increasingly used, and provides a viable alternative to surgery. Estrogen and progesterone usually stimulate their growth, and hormone suppression may hence decrease their size.

Esophageal

Leiomyoma of the esophagus is the most common benign esophageal tumour, though this accounts for less than 1% of esophageal neoplasms. The remainder consists mainly of carcinomas. Although the vast majority of benign esophageal tumors are clinically silent and go undetected, large or strategically located tumors may become symptomatic.

Leiomyoma of Jejunum

Leiomyoma is the most common benign tumor of small bowel. Approximately 50% of cases are found in the jejunum, followed by the ileum in 31% of cases. Almost one half of all lesions are less than 5 centimeters.

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  Leiomyoma enucleated from a uterus. External surface on left; cut surface on right

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  A large, solitary leiomyoma in the uterus, distoring the endometrial cavity into a Y shape by splaying and pressing it downwards.
  (Image courtesy of Ed Uthman, MD)

Causes

• Chromosome aberrations such as t(12;14)(q14-q15;q23–24), del(7)(q22q32), rearrangements involving 6p21, 10q, trisomy 12, and deletions of 1p3q have been associated with the development of leiomyoma.

Differentiating Leiomyoma from other Diseases

Leiomyoma is a cause of abnormal uterine bleeding and can result in infertility. There are several diseases which can result in excessive uterine bleeding and the following table is a description of various causes of excessive uterine bleeding.

	Clinical Features	Physical Examination	Diagnostic Findings
Endometriosis	Dysmenorrhea Dyspareunia Infertility Common in women between 25 to 35 years	Nodules in the posterior fornix Adnexal masses Fixed retroverted uterus Lateral displacement of the cervix	Increased serum cancer antigen-125  Nodules of the recto vaginal septum and hypoechoic, vascular mass on MRI Laproscopic visualization confirms the diagnosis
Adenomyosis	Abnormal uterine bleeding Dysmenorrhea Common in women aged 40 and 50 years	Diffuse uterine enlargement always less than size corresponding to less than 12 weeks of gestation	Asymmetric thickening of the myometrium on MRI
Submucous uterine leiomyomas	Menorrhagia Pelvic pressure and pain Infertility Peak age of onset 25 to 44 years of age	Mobile uterus with an irregular contour	Transvaginal ultrasound will demonstrate the presence of myomas
Pelvic Inflammatory disease	Seen in patients with history of sexually transmitted disease History of multiple sexual partners  Common in women younger than 25 years of age	Abdominal tenderness  Acute cervical motion, uterine, and adnexal tenderness Visualization of purulent endocervical discharge	Positive Nucleic acid amplification tests for Chlamydia trachomatis and N. gonorrhoeae Gram negative diplococci on gram stain
Pelvic congestion Syndrome	Shifting lower abdominal pain Deep dyspareunia Post-coital pain Exacerbation of pain after prolonged standing	Bimanual tenderness Cervical motion tenderness	Pelvic varicosities on ultrasound with reduced blood flow

Epidemiology and Demographics

Age

• Leiomyoma is more commonly observed among patients aged 40 years and older.

Race

• Leiomyoma usually affects African-American women.

Risk Factors

• Common risk factors in the development of uterine leiomyoma include:
  • African-American race
  • Early menarche
  • Prenatal exposure to diethylstilbestrol
  • Having one or more pregnancies extending beyond 20 weeks
  • Obesity
  • Significant consumption of beef and other reds meats
  • Hypertension
  • Alcohol consumption

Natural History, Complications and Prognosis

• The majority of patients with uterine leiomyoma remain asymptomatic for decades
• Common complications of uterine leiomyoma include:
  • Dysmenorrhea
  • Dyspareunia
  • Leiomyoma degeneration or torsion
  • Transcervical prolapse
  • Miscarriage.

Diagnosis

Symptoms

• Leiomyoma is usually asymptomatic.
• Symptoms of uterine leiomyoma may include the following:

• Abnormal gynecologic hemorrhage
• Heavy or painful periods
• Abdominal discomfort or bloating
• Back ache
• Urinary frequency or retention
• Infertility

Physical Examination

• Physical examination may be remarkable for:

• Enlarged, mobile uterus with an irregular contour on bimanual pelvic examination

Imaging Findings

• On ultrasound imaging, uterine leiomyoma is characterized by the fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the ultrasound beam.

Other Diagnostic Studies

• Uterine leiomyoma may also be diagnosed using diagnostic hysteroscopy, magnetic resonance imaging, and hysterosalpingography.

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Patient #1: MR images demonstrate large degenerating leiomyomas

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Patient #2: MR images demonstrate a leiomyoma prolapsing into the endometrial canal

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Hysterosalpingogram(HSG) reveals a submucosal leiomyoma

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Treatment

Medical Therapy

• The mainstay of therapy for uterine leiomyoma is oral contraceptive pills, either combination pills or progestin-only, Gonadotropin-releasing hormone analogs.

Surgery

• Surgery is the mainstay of therapy for uterine leiomyoma.
• Uterine artery embolization in conjunction with laparotomic myomectomy is the most common approach to the treatment of leiomyoma.
• Hysteroscopic myomectomy can also be performed for patients with uterine leiomyoma.