Leiomyoma

Abel G
(MD,MPH)
Diredaw
University
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 Table of contents
Introduction
Predisposing factors
Pathogenesis & pathology
Clinical features
Pregnancy & leiomyoma
Treatment

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 Introduction
Benign clonal tumor arising from smooth
muscle cells with extracellular matrix
Synonyms = myoma, fibroid, leiomyoma
of uterus, fibromyoma, myofibroma,
fibroma, leiomyofibroma, fibroleiomyoma
Most common tumor of uterus and female
pelvis
Parallels with the ontogeny & life cycle change
of reproductive hormones
Most common indication for hysterectomy in
USA-175,000/year
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 Occurs in 20-40% of reproductive age
women
Rare in women < 18 years of age, a report
at 1 year of age
Responsible for one third of gynecologic
admissions
Postmenopausal incidence is not lower than
premenopausl.

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 Predisposing factors
Contribute either to initiation or promotion
The most consistent factors are age and black
race.
Many of the factors effect is attributed to their
effects on estrogens & progesterone
Factors related to tumorogenesis of leiomyoma
classified as:
Predisposing factors
Initiators
Promoters
Effectors

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 Predisposing factors
There is overlap of factors-obesity, diet,
etc
Many of the factors effect is attributed
to their effects on estrogens &
progesterone
Proving the association is difficult

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1. Menarche: Early menarche
2. Parity:
Having one or more pregnancies beyond 20 weeks
decreases the chance, women at least given birth to
2 children has 2x less risk
3. Age: Reproductive age
4. Obesity: Fibroids increase by
21% for each 10 kg (USA) or
6% increase for each BMI increase (Thailand)

5. Diet:
High intake of beef, red meat & ham increased risk.
High intake of vegetables is to have protective effect
6. Exercise
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7. Racial differences: 3-9 x common in
blacks
Black white
US 73% 48% 1998
Specimen 89% 59% 1996

Myomas in blacks are larger, numerous,

more symptomatic & occur at younger age
basis is not known, estrogen metabolism
8. Geographic differences: Shows importance
of diet, environmental factors & ethnicity
*Prevalence in Nigeria-68% (1981)
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9. Smoking: Reduces risk of fibroid
-10 Cigarettes/day-Decreases risk by 18%
-20 Cigarettes/day-Decreases risk by 33%
Epidemiological association
- decreased endometrial Ca
- Earlier natural menopause
- Increased osteoporosis
10. Oral contraceptives:
17 % reduction in risk with each 5 year use
11. Tamoxifen: weak estrogenic effect-20%

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 Reduces risk
Multiparity
Exercise
Diet:
High intake of vegetables is to have
protective effect
Smoking
Oral contraceptives

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 Pathogenesis and Pathology
A. Initiators of tumorogenesis:
The most important piece of fibroid puzzle
remains unsolved
Three theories:
1. Increased level of estrogen and
progesterone lead to increased mitotic
rate that end in increased somatic mutation

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 2. A response to injury
Analogous to development of keloids
potential injury associated with release of
vaso-constrictve substances (PGs &
vasopressin)
Smooth muscle cells react by changing
from contractile type to proliferative type
Worthy in view of menstration &
commonality of myoma

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3. Theory of genetic and/or epigenetic
changes
Karyotypic changes occur secondarily
Preceding stimuli, condition or injury is
responsible for the induction of genetic &
epigenetic changes
Probable potentiators or effectors of
initiating event
Could be the primary event

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Genetic findings in favor are clonality and
cytogenetic abnormalities of leiomyoma
a. Heritability : Is there genetic
predisposition?
-Ethnic predisposition
- Twin
-familial aggregation: 4.2x
- inherited syndromes

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 Contd
B. Clonality: Based on Lyon hypothesis
- X-linked G6PD: polymorphism
- Methylation Sensitive restriction enzymes: Chromosome 7 biclonality in 4 leiomyomas

C. Cytogenetics: 40-50% has non-random chromosome abnormalities

- Based on G-band analysis & genomic hybridization
Del(7q22;32): occurs in 17%
6p21: Includes deletions, inversions, translocations & insertions
- Occurs in < 5%
Trisomy 12: Occurs in 12%
50% appear cytogenetically normal-point mutation.

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 B. Promoters
Evidence of estrogen and progesterone
1. Clinical observations: develop during
reproductive years, shrinkage with GnRH
analog Rx, etc
2. Laboratory
- 17 estradiol is higher in myoma
- Over expression of aromatase activity
3. Estrogen and progesterone receptors
- Were greater in myoma than
myometrium

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 C. Effectors
The growth promoting effects of E & P upon myometrium
& uterine myoma may be mediated through the
mitogenic effects of growth factors produced locally by
the smooth muscle cells & fibroblasts.
The growth factors include:
1.Transforming growth factor : Mitogenesis &matrix
formation
2. Basic fibroblast growth factor: Mitogenesis &
angiogenesis
3. Epidermal growth factor; Increase during luteal phase
4. Platelet derived growth factor
5. Vascular endothelial growth factor
6. Insulin like growth factor
7. Prolactin
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 Pathology
Gross pathology/Appearance:-
Rare as a single usually multiple
Well-circumscribed non-encapsulated
A pseudo-capsule is present-formed by compressed
adj. myometrium.
The consistency is usually firm or even hard except
when degeneration or hemorrhage has occurred.
color light gray or pinkish white
Microscopic Appearance
Composition smooth muscle, connective tissue
The non-striated muscle fibers are arranged in
bundles of various sizes that run in multiple directions.

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Variants of leiomyoma
1. Mitotically active leiomyoma
2. Cellular leiomyoma: Confused with endometrial stromal
tumor.
3. Bizzare leiomyoma: giant nuclei with multinucleation
4. Epitheloid leiomyoma
5. Intravenous leiomyomatosis
6. Benign metastasizing leiomyoma
7. Peritoneal leiomyomatosis
Immunohistochemical staining for desmin & Muscle specific
actin

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 Classification
According to anatomic location

Intramural 60 70%
Subserosal 20%
Submucous 10 15%
Cervical
Parasitic

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21
 Manifestation
The vast majority (70%) of leiomyomas are
asymptomatic.
Symptoms could be single or multiple.
Abnormal uterine bleeding:-
The most common symptom of uterine leiomyoma
30% of symptomatic women suffered from
menorrhagia.
The mechanism of fibroid-associated menorrhagia is
unknown, but possible explanations:-
1.ed surface area
2. Endometrial thinning and ulceration
3. Interference with myometrial contraction
4. Associated endometrial hyperplasia
5. Imbalance of prostaglandin(TXA2vs.PGI2).
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Pelvic pain occurs in 30% symptomatic and it
usually signifies degeneration, torsion, or,
possibly, associated adenomyosis
Pressure symptoms:-
Bowel dysfunction ( constipation, obstruction)
Bladder symptoms such as urinary frequency and
urgency
Reproductive dysfunction
Others ( abdominal distortion, anemia,
polycythemia
NB: In the postmenopausal woman presenting with pain
and fibroids, leiomyosarcoma should be considered.

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 Life threatening complications
of myoma
Persistent menorrhagia - severe anaemia.
Severe intraperitonial haemorrhage.
Severe infection peritonitis or septicemia.
Sarcoma.

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 Pregnancy & Myoma
Increase during pregnancy: 22%
Effect of myoma on pregnancy
- Abortion
- Malpresentation: 4x
- Placental abruption: 4x
- Dysfunctional labour, obstructed labour
- Increased operative delivery: C/S-6x
- PPH etc
-IUGR
-Preterm labor
Red degeneration

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 Degeneration
Hyaline degeneration Result from the diminished
the commonest
Cystic degeneration vascularity of the
Red (carneous) degeneration connective-tissue element
During pregnancy or immediate postpartum period
The pathogenesis is unknown may be the result
of the accumulation of blood in the tumour
because of venous obstruction
The cut surface resembles raw meat.
Clinical features a cause of pain (acute), fever,
rapid growth tender
Sarcomatous (malignant) degeneration-rare
less than 0.1%.
Others
Fatty (myxomatous) degeneration,
Atrophic (esp post menapause),
Calcification (womb stones),
Septic (secondary infection ) degeneration ,
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 Diagnosis
History
Signs
A palpable abdominal tumour
Pelvic examination
uterus enlarged and irregular hard
Investigations:-
CBC,
Ultrasound
Hysterosalpingography
Plain abdominal film
Imaging techniques-US, CT, MRI
laparascopy
Sonohysterography

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 Differential Diagnosis
Pregnancy
Ovarian tumour
Adenomyosis
Malignant tumors of uterus
sarcoma of uterus
endometrial carcinoma
cervical cancer

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 Management
Asymptomatic ones are managed
expectantly
Factors considered prior to initiating treatment:
Size of myoma(s)
Location of myoma(s)*
Symptoms
Womans age (eg menopause)
reproductive plans
It is important to individualize the
choice of therapy.
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 Management could be:
Expectant
Medical
Surgical
Myomectomy
Hysterectomy
Uterine artery embolization
Myolysis
Immunotherapy

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 Observation and Follow Up ( expectant
management):-
Small asymptomatic fibroids need not be
treated especially near menopause.
Interval 3 6 months

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Medical therapy
GnRH analogs:
Decrease in myoma size and bring amenorrhea.
Can also bring hot flushes and osteoporosis.
Reduces size of myoma by 40-50% in 6 months
Danazol: A19-nortestrone derivative with progestin like
effects.
200-400mg daily in divided doses for 3 month.
Gestrinone: Decreases myoma volume & induces
amenorrhea.
Mifeprestone (RU 486)-decrease the size and
menorrhagia.
25-30mg daily for three months.

GnRH antagonists: Citrorelix, ganireflix

Ineffective therapies: OCP & NSAIDS
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 The objectives of medical
treatment.
To minimize blood loss and correct anaemia.
To minimize the size and vascularity.
To facilitate hysteroscopic or laparascopic
surgery.
As alternative to surgery in perimenopausal
women.
Where postponement of surgery is planned
temporarily.

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Surgical management:-
Indications:
AUB
Pelvic discomfort due to myoma
Reproductive dysfunction- infertility &
recurrent pregnancy loss
Method:-
Myomectomy:-
Approach
o trans-abdominal
o trans-vaginal
o laparoscopic or
o hysteroscopic
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Hysterectomy:
definitive treatment.
Only true cure for leiomyomas
It eliminates current symptoms & risk of recurrence
Others
Uterine artery embolization, UAE, (embolo therapy)
Selective uterine artery occlusion is a treatment
alternative to hysterectomy for women with
symptomatic uterine fibroids, in whom other
medical and surgical treatments are
contraindicated, refused, or ineffective.

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 Pelvic angiogram /UAE

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 Rt uterine artery

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 Myolysis(Myoma coagulation)
Myolysis refers to the procedure of delivering
energy to myomas in an attempt to desiccate
them directly or disrupt their blood supply
Immunotherapy
RESAN:
It triggers a specific T-cell immune
response against uterine myoma
Candidates are young age, small size
myoma, Intramural, slow rate of growth
Interferon
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 References
1. Leiomyomata uteri & myomectomy, Te Lindes operative gynecology, 9 th
edition, 2003
2. Uterine fibroids, obstetric & gynecology clinics of north America, 1995;22:4
3. Uterine fibroids, obstetric & gynecology clinics of north America,
2000;27:2:397-429
4. Progestrone in the pathogenesis of myoma. American journal of obstetrics &
gynecology1995;172:14-18
5. ACOG practice bulletin 2000;16
6. Up to date 10.2 ;2002
7. Duttas text book of gynecology;3rd edition,2001
8. Risk factors & pathogenesis of myoma. Environmental health
perspectives,2003;111:1037-1054
9. Laparascopic myomectomy. Fertility & sterility,2005:83:1-21
10. Add-back therapy with GnRH. British journal of obstetrics &
gynecology,1996;103 sup14:1-4
11. Gasless laparascopic myomectomy. Journal of reproductive
medicine,2003;48:10:793-797
12. Laparascopic myomectomy. Journal of reproductive medicine,2002;47:849-
853
13. Blaustens pathlogy of the female genital tract, 3 rd edition,1987
14. Wiliams obstetrics, 21st edition,2001

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 Thank You!!

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