Uterine leiomyoma

ABERA BEDHADHA (MD, Obstetrician and Gynecologist)

Sept, 2021
 Outline of presentation

Introduction to pelvic mass

Prevalence and risk factors
Clinical features
Diagnostic evaluation
Management options
 Objective

Define uterine leiomyoma and list its risk factors

Identify clinical presentation of patients with uterine leiomyoma

Suggest workup for patients with uterine leiomyoma

List differential diagnosis for uterine leiomyoma

Tell management options for patients with uterine leiomyoma

 Pelvic mass
• Pelvic masses are common and may involve reproductive organs or
nongynecological structures.
• Affected women can be symptom- free or may complain of pain, pressure,
dysmenorrhea, infertility, or uterine bleeding.
 Pelvic mass
• Of associated factors, pelvic mass rates and underlying pathology change with
age.
• In prepubertal girls, most gynecologic pelvic masses involve the ovary.

• Even before puberty, ovaries are active, and masses are often functional, rather
than neoplastic
• In adolescents, the incidence and type of ovarian pathology in general mirrors that
of prepubertal girls.
• With the onset of reproductive function, pelvic masses in adolescence may also
include endometriomas and the sequelae of pelvic inflammatory disease (PID)
and pregnancy
 Pelvic mass
In adult women, the differential diagnosis of a pelvic mass expands.
Uterine enlargement due to pregnancy, functional ovarian cysts, and
leiomyoma are among the most common.
Endometrioma, mature cystic teratoma, acute or chronic tuboovarian
abscess (TOA), and ectopic pregnancies are other frequent causes.
Less often, enlargement is from adenomyosis, hematometra, an
adhered adnexal mass, or malignancy.
Most pelvic masses in this age group are benign, but malignancy rates
increase with age.
 Uterine Leiomyoma
Uterine leiomyomas (also referred to as fibroids or myomas) are the
most common pelvic tumor in women.
They are benign monoclonal tumors arising from the smooth muscle
cells of the myometrium.
They arise in reproductive-age women and typically present with
symptoms of abnormal uterine bleeding and/or pelvic pain/pressure.
Uterine fibroids may also have reproductive effects (eg, infertility,
adverse pregnancy outcomes).
 Uterine Leiomyoma
Grossly, leiomyomas are round, rubbery tumors that when bisected display
a whorled pattern.
They possess a distinct autonomy from their surrounding myometrium
because of a thin, outer connective tissue layer
This clinically important cleavage plane allows leiomyomas to be easily
“shelled” from the uterus during surgery
Histologically, leiomyomas contain elongated smooth-muscle cells
aggregated in dense bundles.
Mitotic activity, however, is rare and is a key point in differentiation from
malignant leiomyosarcoma.
 PREVALENCE
 Uterine leiomyomas are the most common pelvic tumor in women
Incidence is difficult to determine since there are few longitudinal studies
Their incidence among women is generally cited as 20 to 25 percent, but is
as high as 70 to 80 percent in studies using histologic or sonographic
examination
The prevalence of leiomyomas increases with age during the reproductive
years
Leiomyomas have not been described in prepubertal girls, but they are
occasionally noted in adolescents.
Most, but not all, women have shrinkage of leiomyomas after menopause.
 Pathogenesis
Each leiomyoma is derived from a single progenitor myocyte.
Thus, multiple tumors within the same uterus each show independent
cytogenetic origins
Several unique defects involving chromosomes 6, 7, 12, and 14 and others
correlate with rates and direction of tumor growth.
Following their genesis, uterine leiomyomas are estrogen and progesterone
sensitive tumors.
Consequently, they develop during the reproductive years.
After menopause, leiomyomas generally shrink, and new tumor
development is infrequent.
 Pathogenesis
Leiomyomas themselves create a hyperestrogenic environment, which
appears requisite or their growth and maintenance.
First, compared with normal myometrium, leiomyoma cells contain a
greater density of estrogen receptors, which results in greater estradiol
binding.
Secondly, these tumors convert less estradiol to the weaker estrone
A third mechanism involves higher levels of cytochrome P450
aromatase in leiomyomas compared with normal myocytes
This specific enzyme catalyzes the conversion of androgens to estrogen
 Pathogenesis
Of other factors, estrogen and progesterone hormone treatment in
premenopausal women probably has no significant inductive effect on
leiomyoma formation.
With few exceptions, combination oral contraceptive (COC) pills either
lower or have no effect on this risk
Smoking alters estrogen metabolism and lowers physiologically active
serum estrogen levels
This may explain why women who smoke generally have a lower risk or
leiomyoma formation.
 Pathogenesis
As with estrogen, leiomyomas carry a higher progesterone receptor
density compared with their surrounding myometrium.
Progesterone is considered the critical mitogen for uterine leiomyoma
growth and development, and estrogen functions to upregulate and
maintain progesterone receptors
 Risk factors
Some conditions also provide sustained estrogen exposure that
encourages leiomyoma formation.
For example, the increased years of persistent estrogen production
found with early menarche( younger than 10 years) and with an
increased body mass index (BMI) are each linked with a greater
leiomyoma risk
Obese women produce more estrogens from increased conversion of
androgens to estrogen in adipose tissue by aromatase.
Women with polycystic ovarian syndrome (PCOS) have a higher
risk of myoma formation, which may stem from the sustained estrogen
exposure that accompanies chronic anovulation
 Risk factors
Of factors associated with myoma development, race and age are notable risks.
Myomas are rare in adolescence but increase with age during the reproductive
years
Lower rates of leiomyomas are linked with pregnancy.
Those who have higher parity, have had a more recent pregnancy, and have
breast fed all display lower incidences of myoma formation
Leiomyomas are more common in African-American women compared with
white, Asian, or Hispanic women.
Thus, as noted earlier, heredity and specifically gene mutations play a
seminal role in myoma development.
 Uterine Leiomyoma Classification

• These tumors are classifed based on their location and direction of

growth
• Subserosal leiomyomas originate from myocytes adjacent to the
uterine serosa, and their growth is directed outward.
• When these are attached only by a stalk to their progenitor
myometrium, they are called pedunculated leiomyomas.
 Uterine Leiomyoma Classification

• Parasitic leiomyomas are subserosal variants that attach themselves to

nearby pelvic structures from which they derive vascular support.
• These myomas then may or may not detach from the parent myometrium.
• Intramural leiomyomas are those with growth centered within the uterine
walls.
• Finally, submucous leiomyomas are proximate to the endometrium and
grow toward and bulge into the endometrial cavity.
 Clinical features
Uterine leiomyomas are typically brought to medical attention due to
symptoms or are found incidentally on pelvic imaging
Fibroids are almost never associated with mortality, but they may
cause morbidity and significantly affect the quality of life
The majority of myomas are small and asymptomatic, but many women
with fibroids have significant problems that interfere with some aspect of
their lives and warrant therapy
 Clinical features
These symptoms are related to the number, size, and location of
the tumors.
 Myomas can occur as single or multiple tumors and range in size
from microscopic to tens of centimeters.
The size of the myomatous uterus is described in menstrual weeks as
with the gravid uterus
 Clinical features
• Symptoms are classified into three categories :
• Heavy or prolonged menstrual bleeding
• Bulk-related symptoms, such as pelvic pressure and pain
• Reproductive dysfunction (ie, infertility or obstetric
complications)
 Heavy or prolonged menstrual bleeding

Heavy and/or prolonged menses is the typical bleeding pattern with

leiomyomas and the most common fibroid symptom.
Intermenstrual bleeding and postmenopausal bleeding should
prompt investigation to exclude endometrial pathology.
Heavy uterine bleeding may be responsible for associated problems,
such as iron deficiency anemia, social embarrassment, and lost
productivity in the work force.
The presence and degree of uterine bleeding are determined, in large
part, by the location of the fibroid; size is of secondary importance
 Heavy or prolonged menstrual bleeding
• The pathophysiology underlying this bleeding may relate to dilatation of venules.
• Bulky tumors are thought to exert pressure and impinge on the uterine venous
system, which causes venous dilatation within the myometrium and endometrium
• Dysregulation of local vasoactive growth factors is also thought to promote
vasodilatation.
• When engorged venules are disrupted at the time of menstrual sloughing, bleeding
from these markedly dilated venules overwhelms the usual hemostatic mechanisms
• For this reason, subserosal, intramural, and submucous tumors all have a
propensity to cause HMB
 Pelvic Discomfort and Dysmenorrhea.

A sufficiently enlarged uterus can cause pressure sensation, urinary

frequency, incontinence, or constipation.
Rarely, leiomyomas extend laterally to compress the ureter and lead to
obstruction and hydronephrosis.
Although dysmenorrhea is common, women with leiomyomas more
frequently had dyspareunia or noncyclical pelvic pain than dysmenorrhea.
 Acute Pelvic Pain.
This is a less frequent complaint with leiomyomas, but is most often
seen with a degenerating or prolapsing leiomyoma.
As described earlier, leiomyomas may degenerate, and such tissue
necrosis can be associated with acute pain, fever, and leukocytosis
Women with prolapse of a tumor from the endometrial cavity will
typically present with complaints of cramping or acute pain as the
tumor stretches and passes through the endocervical canal.
 Acute Pelvic Pain.
Associated bleeding or serosanguineous discharge is common.
Visual inspection is usually diagnostic, although sonography is often
performed to evaluate the size and number of coexisting uterine
leiomyomas and exclude other possible sources of pain
In leiomyomas not immediately removed, preoperative biopsy may be
indicated because some cases of uterine sarcoma or cervical cancer
can appear similar.
 Acute Pelvic Pain
• Acute pain may also follow rare complications such as
• Torsion of a subserosal pedunculated leiomyoma
• Acute urinary retention
• Deep-vein thromboembolism, or
• Intraperitoneal hemorrhage
 Infertility and Pregnancy Wastage
• Although the mechanisms are not clear, leiomyomas can be associated
with infertility
• It is estimated that 2 to 3 percent of infertility cases are due solely to
leiomyomas
• Leiomyomas that distort the uterine cavity (submucosal or intramural
with an intracavitary component) result in difficulty conceiving a
pregnancy and an increased risk of miscarriage
• Their putative effects include occlusion of tubal ostia and disruption
of the normal uterine contractions that propel sperm or ova.
 Infertility and Pregnancy Wastage
• Distortion of the endometrial cavity may also diminish implantation and sperm
transport.
• Importantly, leiomyomas are associated with endometrial inflammation and
vascular changes that may disrupt implantation
• submucosal fibroids decreases fertility and removing them can increase fertility;
• subserosal fibroids do not affect fertility and removing them does not increase
fertility;
• intramural fibroids may slightly decrease fertility, but removal does not increase
fertility.
 Pregnancy on myoma
• The prevalence of uterine fibroids in pregnancy varies between 1.6
and 10.7 percent, depending upon the trimester of assessment and the
size threshold
• Pregnancy-related increases in estrogen and progesterone levels,
uterine blood flow, and possibly human chorionic gonadotropin levels,
are believed to affect fibroid growth
• It appears that fibroid size remains stable (<10 percent change) across
gestation in 50 to 60 percent of cases, increases in 22 to 32 percent,
and decreases in 8 to 27 percent
 Pregnancy on myoma
• Most pregnant women with fibroids do not have any complications
during pregnancy related to the fibroids
• When complications occur, painful degeneration is the most common
complication.
• Rapid growth of fibroids can result in a relative decrease in perfusion,
leading to ischemia and necrosis (red degeneration) and release of
prostaglandins.
• Pedunculated fibroids are at risk of torsion and necrosis, but this is
much less common than degeneration.
 Myoma and pregnancy
• The presence of myoma during pregnancy have been associated with
adverse pregnancy outcomes
• Placental abruption,
• Fetal growth restriction,
• Malpresentation, and
• Preterm labor and birth
• Dysfunctional labour, Ceaserean delivery
• PPH
 Endocrine effects
• Rare symptoms of fibroid tumors where fibroids can secrete ectopic
hormones include:

• Myomatous erythrocytosis syndrome.

• Less than 0.5 percent o women with leiomyomas develop myomatous
erythrocytosis syndrome.
• This may result rom excessive erythropoietin production by the kidneys or
by the leiomyomas themselves.
• In either case, red cell mass returns to normal following hysterectomy.
 Endocrine effects
• Pseudo-Meigs syndrome
• Leiomyomas occasionally may cause pseudo-Meigs syndrome
• Traditionally, Meigs syndrome consists of ascites and pleural effusions that accompany a
benign ovarian fibroma.
• However, any pelvic tumor including large, cystic leiomyomas or other benign ovarian
cysts can cause this.
• The presumed etiology stems from discordancy between the arterial supply and the
venous and lymphatic drainage from the leiomyomas.
• If due to myomas, resolution of ascites and hydrothorax follows hysterectomy or
myomectomy.
• Hypercalcemia from autonomous production of parathyroid hormone-related
protein
 DIAGNOSTIC EVALUATION

• The clinical diagnosis of uterine leiomyomas is made based upon a

pelvic examination and pelvic ultrasound findings consistent with a
uterine leiomyoma.
• The most common symptoms are heavy or prolonged menstrual
bleeding, and fibroids may be associated with pelvic pain, infertility,
or other symptoms.
• Typically, the clinical diagnosis is confirmed with a pelvic ultrasound.
 DIAGNOSTIC EVALUATION
• A definitive diagnosis is made by pathology evaluation but histologic
confirmation of the clinical diagnosis is not necessary in most cases
• The pelvic examination findings are typically of an enlarged, mobile
uterus with an irregular contour on bimanual pelvic examination;
however, small submucosal or intramural fibroids will not produce a
noticeably enlarged uterus or an irregular contour.
 Imaging
• Sonography
•  Pelvic ultrasound is the imaging study of choice for uterine leiomyomas.
• Is initially done to define pelvic anatomy
• The sonographic appearances of leiomyomas vary from hypo- to hyperechoic depending on
the ratio of smooth muscle to connective tissue and whether there is degeneration.
• Saline infusion sonography (SIS) or hysteroscopy
• If menorrhagia, dysmenorrhea, or infertility accompanies a pelvic mass, then the
endometrial cavity may be evaluated for submucous leiomyomas, endometrial polyps,
congenital anomalies, or synechiae.
• If the endometrium is thick or irregular, then saline infusion sonography (SIS) or
hysteroscopy may provide additional information
• Hysterosalpingography (HSG)
• For the infertile woman, hysterosalpingography (HSG) may be used during initial evaluation
to define endometrial pathology as well as tubal patency.
Sonography
Saline infusion sonography and
Hysteroscopy
Saline infusion sonography (sonohysterography) is an imaging study in which pelvic ultrasound is
performed while saline is infused into the uterine cavity.
 Imaging
• Doppler imaging
• Leiomyomas have characteristic vascular patterns that can be identified by
color flow Doppler.
• A peripheral rim of vascularity from which a few vessels arise to penetrate
into the center of the tumor is traditionally seen.
• Doppler imaging can be used to differentiate an extrauterine leiomyoma from
other pelvic masses or a submucous leiomyoma from an endometrial polyp or
adenomyosis
 Magnetic resonance imaging

• May be required when imaging is limited by body habitus or distorted

anatomy.
• This tool allows more accurate assessment of the size, number, and location of
leiomyomas, which may help identify appropriate patients for alternatives to
hysterectomy such as myomectomy or uterine artery embolization
• Importantly, for a dominant fundal uterine mass, MR imaging can also aid
differentiation of a fundal leiomyoma, which is a suitable myomectomy
indication, from adenomyosis, which is an unsuitable indication for this
procedure
 DIAGNOSTIC EVALUATION

• Laboratory testing 
• Laboratory testing does not have a role in the diagnosis of uterine
leiomyomas.
• If a patient has long-term heavy or prolonged menstrual bleeding, a hematocrit
may be ordered to evaluate for anemia.
• A urine or serum human chorionic gonadotropin is ordered if the patient may
be pregnant.
 DIFFERENTIAL DIAGNOSIS 
• The differential diagnosis of uterine leiomyomas includes other
conditions that cause uterine enlargement, abnormal uterine bleeding
(AUB), pelvic pain, or infertility.

• It is important to note that leiomyomas are a common condition, and

other coexisting conditions may be the etiology of the presenting
symptoms.
• The differential diagnosis of an enlarged uterus includes both benign and
malignant conditions:
• Myometrial lesions:
•Benign leiomyoma.
•Adenomyosis (diffuse infiltration of the myometrium) or adenomyoma.
•Leiomyoma variant.
•Leiomyosarcoma.
• Endometrial lesions:
• Endometrial polyp – These tend to be small and are unlikely to cause an enlarged uterus.
• Endometrial carcinoma (may invade into the myometrium) or hyperplasia.
• Carcinosarcoma – Considered an epithelial neoplasm.
• Endometrial stromal sarcoma (mimics endometrium but invades the myometrium).
• Pregnancy
• Hematometra (blood within the uterine cavity, usually following an intrauterine
procedure, eg, dilation and curettage)
 Differential diagnosis
• Pregnancy should be excluded in any woman of reproductive age
who presents with an enlarged uterus, AUB, and/or pelvic pain.
• Most commonly, when faced with an enlarged uterus, uterine
leiomyomas must be differentiated from uterine adenomyosis.
• Women with adenomyosis more often present with a diffusely
enlarged uterus, painful menses, and AUB.
• On examination in a woman with adenomyosis, the uterus is
typically smooth, globular, and boggy.
 Management
Observation
• Regardless of their size, asymptomatic leiomyomas usually can be
observed and surveilled during annual pelvic examination
• However, assessment of the adnexa may be hindered by uterine size or
contour, and adequate uterine and adnexal assessment may be limited by
patient obesity.
• In these cases, some may choose to add annual sonographic
surveillance
 Observation
• Leiomyomas in general are slow-growing.
• Moreover, growth rates of leiomyomas within the same patient will
vary widely, and some tumors will even spontaneously regress
• Therefore, predicting leiomyoma growth or symptom onset is difficult,
and watchful waiting may be the best option for an individual
asymptomatic patient.
 Observation
• In the past, most preferred surgical removal of a large, asymptomatic
leiomyomatous uterus because of concerns regarding cancer risks and
increased operative morbidity if left to grow larger.
• These concerns have been disproven, and thus, otherwise asymptomatic
women with large leiomyomas can also be managed expectantly
• In addition, most infertile women with uterine leiomyomas are
initially managed expectantly.
• For those with symptomatic tumors, surgery should be timed closely to
planned pregnancy, if possible, to limit the risk of tumor recurrence
 Symptomatic myoma
• Relief of symptoms (eg, abnormal uterine bleeding, pain, pressure) is
the major goal in management of women with significant symptoms
• The type and timing of any intervention should be individualized,
based upon factors such as
• Type and severity of symptoms
• Size of the myoma(s)
• Location of the myoma(s)
• Patient age
• Reproductive plans and obstetrical history
 Drug Therapy
• In some women with symptomatic leiomyomas, medical therapy may
be preferred.
• In addition, because leiomyomas typically regress postmenopausally,
some women choose medical treatment to relieve symptoms in
anticipation of menopause.
• In others, medical therapy such as GnRH agonists is used as an
adjunct to surgery.
 Surgical Management
• Bleeding and pain symptoms may improve in many women
using medical treatment or radiologic interventions.
• However, for many, surgery for leiomyomas is necessary and includes
hysterectomy, myomectomy, and myolysis

• The following are indications for surgical therapy:

• Abnormal uterine bleeding or bulk-related symptoms
• Infertility or recurrent pregnancy loss
 Myomectomy 
• Myomectomy is an option for women who have not completed
childbearing or otherwise wish to retain their uterus.
• Although myomectomy is an effective therapy for heavy menstrual
bleeding and pelvic pressure, the disadvantage of this procedure is the
risk that more leiomyomas will develop from new clones of
abnormal myocytes.
• Myomectomy usually improves pain, infertility, or bleeding.
• menorrhagia improves in approximately 70 to 80 percent of patients
following tumor removal
 Hysterectomy
• Removal of the uterus is the definitive and most common surgical
treatment for leiomyomas
• The main advantage of hysterectomy over other invasive interventions
is that it eliminates both current symptoms and the chance of
recurrent problems from leiomyomas
 Hysterectomy
• Hysterectomy is indicated for

• (1) women with acute hemorrhage who do not respond to other therapies;
• (2) women who have completed childbearing and have current or increased
future risk of other diseases
• (3) women who have failed prior minimally invasive therapy for leiomyomas
• (4) women who have completed childbearing and have significant symptoms,
multiple leiomyomas, and a desire for a definitive end to symptomatology.
 Summary
• Fibroids are very common; most are asymptomatic and can be managed
expectantly
• Sonography is the most readily available and least costly imaging
technique to differentiate fibroids from other pelvic pathology
• Pregnancy should be excluded in any woman of reproductive age who
presents with an enlarged uterus, AUB, and/or pelvic pain.
• Removal of the uterus is the definitive and most common surgical
treatment for leiomyomas
 References
• Williams gynecology 3rd edition
• Berek and Novak’s gynecology 16th edition
• Ultrasonography in Obstetrics and Gynecology 2nd Edition
• Uptodate 2018