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

# 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;q2324), 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 red 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
- Uterine 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% intramural
Subserosal myomas
FIGO types 6 and 7
Derived from myometrium at the at the serous surface of the uterus
Cervical myomas
FIGO type 8
Usually located in the cervix
- Intramural myomas
FIGO types 3, 4, and 5
Located within the uterine wall
- 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% intramural
- 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% intramural
- Type 0: pedunculated intracavitary
- Type 1: < 50% intramural
- Type 2:  50% intramural
- Subserosal myomas
FIGO types 6 and 7
Derived from myometrium at the at the serous surface of the uterus
- FIGO types 6 and 7
- Derived from myometrium at the at the serous surface of the uterus
- Cervical myomas
FIGO type 8
Usually located in the cervix
- FIGO type 8
- Usually located in the cervix
- Leiomyoma may be classified according to histology features into two subtypes of bening and malignant:
Bening
Mitotically active leiomyomas
Myxoid leiomyomas
Epithelioid leiomyomas
Dissecting leiomyomas
Neoplasm with uncertain clinical behavior
Smooth muscle tumors of uncertain malignant potential
Leiomyoma with bizarre nuclei
Cellular leiomyomas
Neoplasm with extrauterine disease
Leiomyomatosis peritonealis disseminata
Intravenous leiomyomatosis
Benign metastasizing leiomyomas
Multiorgan or primary extrauterine neoplasms
Hereditary leiomyomatosis and renal cell carcinoma syndrome
Lymphangioleiomyomatosis
Cowden syndrome
Vulvar and esophageal leiomyomatosis
- Bening
Mitotically active leiomyomas
Myxoid leiomyomas
Epithelioid leiomyomas
Dissecting leiomyomas
- Mitotically active leiomyomas
- Myxoid leiomyomas
- Epithelioid leiomyomas
- Dissecting leiomyomas
- Neoplasm with uncertain clinical behavior
Smooth muscle tumors of uncertain malignant potential
Leiomyoma with bizarre nuclei
Cellular leiomyomas
- Smooth muscle tumors of uncertain malignant potential
- Leiomyoma with bizarre nuclei
- Cellular leiomyomas
- Neoplasm with extrauterine disease
Leiomyomatosis peritonealis disseminata
Intravenous leiomyomatosis
Benign metastasizing leiomyomas
- Leiomyomatosis peritonealis disseminata
- Intravenous leiomyomatosis
- Benign metastasizing leiomyomas
- Multiorgan or primary extrauterine neoplasms
Hereditary leiomyomatosis and renal cell carcinoma syndrome
Lymphangioleiomyomatosis
Cowden syndrome
Vulvar and esophageal leiomyomatosis
- Hereditary leiomyomatosis and renal cell carcinoma syndrome
- Lymphangioleiomyomatosis
- Cowden syndrome
- Vulvar and esophageal leiomyomatosis

# 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.
- It is thought that leiomyoma is the result of either transformation of normal uterine muscle cells into abnormal cells through somatic mutations, or through the growth of abnormal uterine muscle cells into tumors.
- Genetic mutations involved in the pathogenesis of leiomyoma include: 
t(12;14)(q14-q15;q2324)
del(7)(q22q32)
Rearrangements involving 6p21, 10q, trisomy 12
Deletions of 1p3q
- t(12;14)(q14-q15;q2324)
- del(7)(q22q32)
- Rearrangements involving 6p21, 10q, trisomy 12
- Deletions of 1p3q
- On gross pathology, round, well circumscribed, non-encapsulated, solid white or tan nodules, and whorled are characteristic findings of leiomyoma.
- On microscopic histopathological analysis, elongated and spindle-shaped cells with a cigar-shaped nucleus are characteristic findings of leiomyoma.

# Causes
- Chromosome aberrations in uterine leiomyoma include:
T(12;14)(q14-q15;q2324)
Deletion of (7)(q22q32)
Rearrangements involving 6p21, 10q
Trisomy 12
Deletion of 1p3q have been associated with the development of leiomyoma
- T(12;14)(q14-q15;q2324)
- Deletion of (7)(q22q32)
- Rearrangements involving 6p21, 10q
- Trisomy 12
- Deletion of 1p3q have been associated with the development of leiomyoma

# Differentiating Leiomyoma from other Diseases

# Epidemiology and Demographics

## Age
- Leiomyoma commonly affects individuals between menarche and menopause.
- The incidence increases with age during reproductive years.

## Race
- Leiomyoma usually affects African-American women.
Incidence rates are approximately threefold greater in African-American women than in white women.
- Incidence rates are approximately threefold greater in African-American women than in white women.

# Risk Factors
- Common risk factors in the development of uterine leiomyoma include:
African-American race
Early menarche
Prenatal exposure to diethylstilbestrol
Parity
Having one or more pregnancies extending beyond 20 weeks
Obesity
Diet
Significant consumption of beef and other reds meats
Vitamin D deficiency
Alcohol consumption
Smoking
Hormonal contraception
- African-American race
- Early menarche
- Prenatal exposure to diethylstilbestrol
- Parity
Having one or more pregnancies extending beyond 20 weeks
- Having one or more pregnancies extending beyond 20 weeks
- Obesity
- Diet
Significant consumption of beef and other reds meats
Vitamin D deficiency
- Significant consumption of beef and other reds meats
- Vitamin D deficiency
- Alcohol consumption
- Smoking
- Hormonal contraception

# Natural History, Complications and Prognosis
- The majority of patients with uterine leiomyoma remain asymptomatic for a long time; they are usually found incidentally on imaging or examined after patients start having symptoms.
- Studies have shown that  7 to 40% of premenopausal patients with leiomyoma may witness regression of fibroids over 6 months to 3 years.
- At menopause most fibroids will start to shrink as menstrual cycles stop and hormone levels wane.
- Common complications of uterine leiomyoma include:
Dysmenorrhea
Dyspareunia
Leiomyoma degeneration or torsion
Transcervical prolapse
Miscarriage
- Dysmenorrhea
- Dyspareunia
- Leiomyoma degeneration or torsion
- Transcervical prolapse
- Miscarriage
- Less common complications of uterine leiomyoma include:
Venous compression
Polycythemia from autonomous production of erythropoietin
Hypercalcemia from autonomous production of parathyroid hormone-related protein
Hyperprolactinemia
- Venous compression
- Polycythemia from autonomous production of erythropoietin
- Hypercalcemia from autonomous production of parathyroid hormone-related protein
- Hyperprolactinemia

# Diagnosis

## Diagnostic Study of Choice
- The diagnosis of uterine leiomyoma is based on a clinical diagnosis, which includes a pelvic exam and pelvic ultrasound finding of leiomyomas.
- A pelvic ultrasound is indicated when patients suffer from symptoms of leiomyoma.
- A biopsy is usually not needed to make the diagnosis, but should be performed if clinician is suspicious that the mass is not a fibroid.

## Symptoms
- The majority of patients with leiomyoma are usually asymptomatic.
- Symptoms of uterine leiomyoma may include the following:
- Abnormal uterine bleeding
- Heavy or prolonged menstrual bleeding
- Painful sexual intercourse
- Abdominal discomfort or bloating
- Back pain
- Urinary frequency
- Urinary retention
- Constipation
- Infertility

## Physical Examination
- Common physical examination findings of uterine leiomyoma include enlarged, mobile uterus with an irregular contour on bimanual pelvic examination.

## Imaging Findings
- Pelvic ultrasound is helpful in the diagnosis of uterine leiomyoma.
- Findings on an ultrasound diagnostic of uterine leiomyoma include 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.

# Treatment

## Medical Therapy
- Uterine leiomyomas usually shrink and regress during menopause and the postpartum period.
- Literature is lacking concerning the medical therapy for leiomyoma, and due to their self-limited nature, expectant management is considered in some cases.
- Pharmacologic medical therapy in the form of oral contraceptives is recommended among premenopausal patients with mild symptoms and mildly enlarged uteri.
- Pharmacologic medical therapies for leiomyoma include:
Estrogen-progestin contraceptives
Levonorgestrel-releasing intrauterine system
Progestin implants, injections, and pills
Progesterone receptor modulators
Ulipristal acetate
Mifepristone
Gonadotropin-releasing hormone agonists
Nonsteroidal anti-inflammatory drugs
Danazol and gestrinone
- Estrogen-progestin contraceptives
- Levonorgestrel-releasing intrauterine system
- Progestin implants, injections, and pills
- Progesterone receptor modulators
- Ulipristal acetate
- Mifepristone
- Gonadotropin-releasing hormone agonists
- Nonsteroidal anti-inflammatory drugs
- Danazol and gestrinone

## 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.
- Surgical indications of leiomyoma include followings:
Abnormal uterine bleeding or bulk-related symptoms
Infertility or recurrent pregnancy loss
- Abnormal uterine bleeding or bulk-related symptoms
- Infertility or recurrent pregnancy loss
- There is different types of surgery for leiomyoma include followings:
Hysterectomy
Myomectomy
Endometrial ablation
Myolysis
Uterine artery occlusion
- Hysterectomy
- Myomectomy
- Endometrial ablation
- Myolysis
- Uterine artery occlusion