Leiomyomas

Endometriosis

asistent universitar, d.ș.m.,

Rodica Catrinici
Leiomyomas
 benign smooth muscle neoplasms that typically
originate from the myometrium, often referred to as
uterine myomas and incorrectly called fibroids
because the considerable amount of collagen
contained in many of them creates a fibrous
consistency
 Their incidence among women is generally cited as
20 to 25 %
 In many women, leiomyomas are clinically
insignificant. In some, their number, size, or location
within the uterus can provoke a myriad of symptoms
Pathologic Appearance

 leiomyomas are round, pearly white, firm, rubbery tumors

 A typically involved uterus contains 6 to 7 tumors of varying size
 Leiomyomas possess a distinct autonomy from their
surrounding myometrium because of a thin outer connective
tissue layer. This clinically important arrangement allows
leiomyomas to be easily "shelled out" of the uterus during
surgery!
 Histologically, leiomyomas contain elongated smooth muscle
cells aggregated in bundles. Mitotic activity is rare and is a key
point in differentiation from leiomyosarcoma
Pathologic Appearance

 The appearance of leiomyomas may vary when

normal muscle tissue is replaced with various
degenerative substances following hemorrhage and
necrosis – degeneration. Degeneration develops
frequently in leiomyomas because of the limited
blood supply within these tumors. Acute pain may
accompany degeneration.
Cytogenetics

 Each leiomyoma is derived from a single

progenitor myocyte

 The primary mutation initiating tumorigenesis

is unknown, but a number of unique defects
involving chromosomes 6, 7, 12, and 14
have been identified to correlate with rates
and direction of tumor growth
Role of Hormones

 Uterine leiomyomas are estrogen- and progesterone-

sensitive tumors. Consequently, they develop during the
reproductive years and regress in size and incidence after
menopause.
 Leiomyomas themselves create a hyperestrogenic
environment, which appears requisite for their growth and
maintenance
 Because pregnancy is a progesterone-dominant state, it should
provide an interlude from chronic estrogen exposure and
should discourage leiomyoma development.
 Classification of Uterine Leiomyomas

Leiomyomas are classified 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.
 Parasitic leiomyomas are subserosal variants that attach
themselves to nearby pelvic structures from which they derive
vascular support, and then may or may not detach from the
parent myometrium.
 Intramural leiomyomas are those with growth centered within
the uterine walls.
 Submucous leiomyomas are proximate to the endometrium and
grow toward and bulge into the endometrial cavity.
Symptoms

 Most women with leiomyomas are

asymptomatic
 Symptomatic patients typically complain of
bleeding, pain, pressure sensation, or
infertility
 The larger the leiomyoma, the greater the
amount of symptoms
Symptoms

Bleeding

 is the most common symptom and usually presents

as menorrhagia.
 tumors are thought to exert pressure and impinge on
the uterine venous system, which causes venular
dilatation within the myometrium and endometrium
 Dysregulation of local vasoactive growth factors are
also thought to promote vasodilatation
Symptoms

Pelvic Discomfort and Dysmenorrhea

 A sufficiently enlarged uterus can cause
pressure sensation, urinary frequency,
incontinence, and constipation.
 Rarely, leiomyomas extend laterally to
compress the ureter and lead to obstruction
and hydronephrosis.
Symptoms

Infertility and Pregnancy Wastage

 infertility effects of leyomiomas include occlusion of

tubal ostia and disruption of the normal uterine
contractions that propel sperm or ova
 Distortion of the endometrial cavity may diminish
implantation and sperm transport.
 leiomyomas are associated with endometrial
inflammation and vascular changes that may disrupt
implantation
Symptoms

Other Clinical Manifestations

 Less than 0. 5 percent of women with leiomyomas develop

myomatous erythrocytosis syndrome. This results from
excessive erythropoietin production by the kidneys or by the
leiomyomas themselves. In either case, red cell mass returns to
normal after hysterectomy.

 Leiomyomas occasionally may cause pseudo-Meigs syndrome.

Meigs syndrome consists of ascites and pleural effusions that
accompany benign ovarian fibromas. Resolution of ascites and
hydrothorax follows hysterectomy
Diagnosis

 Leiomyomas are often detected by pelvic

examination with findings of uterine enlargement,
irregular contour.

Imaging (USG)
- sonographic appearances of leiomyomas vary from
hypo- to hyperechoic, depending on the ratio of
smooth muscle to connective tissue and whether
there is degeneration
- Calcification and cystic degeneration create the most
sonographically distinctive changes
◄intramural leyomioma
with calcified borders
Diagnosis
Imaging

 If menorrhagia, dysmenorrhea, or infertility accompanies a pelvic mass, then

the endometrial cavity should be evaluated for submucous leiomyomas

 Saline-infusion sonography (SIS), hysteroscopy, and hysterosalpingography

(HSG) may also have a role in diagnosis.

 Leiomyomas have characteristic vascular patterns that can be identified by

color flow Doppler

 Magnetic resonance (MR) imaging may sometimes be required. 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
Management

Observation

 asymptomatic leiomyomas usually can be managed

expectantly by annual pelvic examination
 asymptomatic women with large leiomyomas can be
managed expectantly
 For those with symptomatic tumors, surgery should
be timed closely to planned pregnancy, if possible, to
limit the risk of leiomyoma recurrence
Management. Drug Therapy
 In some women with symptomatic leiomyomas, medical therapy may
be preferred

Nonsteroidal Anti-Inflammatory Drugs

 Women with dysmenorrhea have higher endometrial levels of
prostaglandins F2 and E2 than asymptomatic women. Accordingly,
treatment of dysmenorrhea and menorrhagia associated with
leiomyomas is based on the role of prostaglandins as mediators of
these symptoms
Hormonal Therapy
 Both combination oral contraceptive pills (COCs) and progestins
have been used to induce endometrial atrophy and decrease
prostaglandin production in women with leiomyomas
 Androgens - both danazol and gestrinone have been found to shrink
leiomyoma volume and improve bleeding symptoms
Management. Drug Therapy

GnRH (Gonadotropine-Releasing Hormone) Agonists

 They are inactive if taken orally, but intramuscular,

subcutaneous, and intranasal preparations are available
 These drugs shrink leiomyomas by targeting the growth effects
of estrogen and progesterone
 Most women experience a mean decrease in uterine volume of
40 to 50 percent, with most shrinkage occurring during the first
3 months of therapy
 Clinical benefits of reduced leiomyoma volumes include pain
relief and diminished menorrhagia
 Unfortunately, leiomyomas then regrow and uterine volumes
regain pretreatment sizes within 3 to 4 months
Management. Drug Therapy
GnRH (Gonadotropine-Releasing Hormone) Agonists

 Side effects result from a profound drop in serum estrogen levels and include
vasomotor symptoms, libido changes, and vaginal epithelium dryness. 6 months of
agonist therapy can result in a 6 percent loss in trabecular bone. To obviate the
severity of these side effects, several medications have been added to GnRH
agonist treatment. Add-back therapy is typically begun 1 to 3 months following
GnRH agonist initiation. Add-back therapy traditionally includes estrogen combined
with a progestin.
Management. Drug Therapy
GnRH Antagonists (cetrorelix, Nal-glu ) - although their profound
hypoestrogenic effects are similar to those of GnRH agonists, they
avoid the initial gonadotropin flare and have a more rapid action. Daily
subcutaneous injections induce leiomyoma shrinkage comparable with
GnRH agonists.

Antiprogestins (Mifepristone)

 Mifepristone diminishes leiomyoma volume by approximately

half.
 Various doses have been used and include 5, 10, 25, or 50 mg
given orally daily during 12 weeks
 Mifepristone therapy, however, has several drawbacks. 40
percent of treated women complain of vasomotor symptoms.
Serum levels of hepatic transaminases become elevated in
about 4 percent of women
Management

Uterine Artery Embolization

 This is an angiographic interventional procedure that delivers

polyvinyl alcohol (PVA) microspheres or other particulate
emboli into both uterine arteries. blood flow is therefore
obstructed, producing ischemia and necrosis. Because vessels
serving leiomyomas have a larger caliber, these microspheres
are preferentially directed to the tumors, sparing the
surrounding myometrium.

 An angiographic catheter is placed in either femoral artery and

advanced under fluoroscopic guidance to selectively
catheterize both uterine arteries
 Management. Uterine Artery
Embolization

 As a result of leiomyoma necrosis, there typically are significant

postprocedural symptoms—the postembolization syndrome.
This usually lasts 2 to 7 days, and it is classically marked by
pelvic pain and cramping, nausea and vomiting, low-grade
fever, and malaise.
 There are a number of complications associated with UAE.
Transient amenorrhea, which lasts at most a few menstrual
cycles. Rarely, serious complications occur following
embolization and include necrosis of surrounding tissues such
as the uterus, adnexa, bladder, and soft tissues.
 Increased risks for preterm delivery and malpresentation in
women who were treated by UAE when compared with
pregnancies that followed laparoscopic myomectomy.
 Increased incidence of abnormal placentation has also been
identified
Surgical Management

Hysterectomy

 Removal of the uterus is the definitive and most

common surgical treatment for leiomyomas
 Hysterectomy for leiomyoma can be performed
vaginally, abdominally, or laparoscopically. Removal
of the ovaries is not required. In some cases,
preoperative GnRH agonist use may provide
advantages.
 There were marked improvements in pelvic pain,
urinary symptoms, fatigue, psychological symptoms,
and sexual dysfunction after hysterectomy.
Surgical Management

Myomectomy

 Resection of tumors is an option for symptomatic

women who desire future childbearing or for those
who decline hysterectomy
 This can be performed laparoscopically,
hysteroscopically, or via laparotomy incision
 Myomectomy usually improves pain, infertility, or
bleeding.
Surgical Management

Laparoscopic Myomectomy
 Limitations to a laparoscopic approach, however,
include uterine size and laparoscopic surgical skills,
especially suturing techniques. Several investigators
have recommended limiting resection to those
tumors less than 8 to 10 cm because of increased
hemorrhage and operating time with larger tumors
 There are risks associated with laparoscopic
myomectomy. Excision sites have been associated
with uteroperitoneal fistula or with uterine rupture
during subsequent pregnancy
Surgical Management

Hysteroscopy
 Resection of submucous leiomyomas through a
hysteroscope has long-term effectiveness of 60 to 90
percent for the treatment of menorrhagia
 Hysteroscopic leiomyoma resection also improves
fertility rates, especially when tumors are the sole
cause of infertility

Endometrial Ablation

Myolysis - includes mono- or bipolar cautery, laser

vaporization, or cryotherapy
Endometriosis: Introduction

 a common benign gynecologic disorder defined as

the presence of endometrial glands and stroma
outside of the normal location.
 endometriosis is most commonly found on the pelvic
peritoneum but may also be found on the ovaries,
rectovaginal septum, ureter, and rarely in the
bladder, pericardium, and pleura
 Endometriosis is a hormonally dependent disease
and as a result is chiefly found in reproductive-aged
women.
Endometriosis: Ethiology

Several theories with supporting evidence have been

described:
1. Retrograde Menstruation
 The earliest and most widely accepted theory
 retrograde menstruation through the fallopian tubes
with subsequent dissemination of endometrial tissue
within the peritoneal cavity
 Refluxed endometrial fragments adhere to and
invade the peritoneal mesothelium and develop a
blood supply, which leads to continued implant
survival and growth
Endometriosis: Ethiology

2. Lymphatic or Vascular Spread

3. Coelomic Metaplasia
 suggests that the parietal peritoneum is a pluripotential tissue
that can undergo metaplastic transformation to tissue
histologically indistinguishable from normal endometrium.

4. Induction Theory
 proposes that some hormonal or biologic factor(s) may induce
the differentiation of undifferentiated cells into endometrial
tissue
 These substances may be exogenous or released directly from
the endometrium
Endometriosis: Ethiology
Hormonal Dependence
 One factor that has been definitively established as having a causative
role in the development of endometriosis is estrogen

 Endometriotic implants have been shown to express aromatase and

17 -hydroxysteroid dehydrogenase, the enzymes responsible for
conversion of androstenedione to estrone and of estrone to estradiol.
This enzymatic combination ensures that implants will be exposed to
an estrogenic environment. Furthermore, the locally produced
estrogens within endometriotic lesions may exert their biologic effect
within the same tissue or cell in which they are produced, a process
referred to as intracrinology.

 This concept of locally produced estrogens and intracrine estrogen

action in endometriosis serves as the basis for pharmacologic
inhibition of aromatase activity in cases of endometriosis that are
refractory to standard therapy
Endometriosis: Ethiology

Role of the Immune System

 Although most women experience retrograde menstruation,

which may play a role in the seeding and establishment of
implants, few develop endometriosis. Menstrual tissue and
endometrium that is refluxed into the peritoneal cavity is usually
cleared by immune cells such as macrophages, natural killer
(NK) cells, and lymphocytes
 For this reason, immune system dysfunction is one likely
mechanism for the genesis of endometriosis in the presence of
retrograde menstruation.
 Impaired cellular and humoral immunity and altered growth
factor and cytokine signaling have each been identified in
endometriotic tissues.
Endometriosis: Risk Factors

 Familial Clustering

 Genetic Mutations and Polymorphisms

 Anatomic Defects - reproductive outflow tract

obstruction can predispose to development of
endometriosis, likely through exacerbation of
retrograde menstruation

 Environmental Toxins
 Classification and Location of
Endometriosis

 endometriosis is classified as stage I (minimal), stage II

(mild), stage III (moderate), and stage IV (severe)

Anatomic Sites
 Endometriosis may develop anywhere within the pelvis
and on other extrapelvic peritoneal surfaces.
 The ovary, pelvic peritoneum, anterior and posterior cul-
de-sac, and uterosacral ligaments are frequently
involved.
 The rectovaginal septum, ureter, and rarely the bladder,
pericardium, surgical scars, and pleura may be affected
Classification and Location of
Endometriosis
Patient Symptoms

Pain - the underlying cause of this pain is unclear, but

proinflammatory cytokines and prostaglandins released
by endometriotic implants into the peritoneal fluid may
be one source
Dysmenorrhea - typically, endometriosis-associated
dysmenorrhea precedes menses by 24 to 48 hours and
is less responsive to nonsteroidal anti-inflammatory
drugs (NSAIDs) and combination oral contraceptives
(COCs).
Dysuria - although less frequent symptoms of
endometriosis, bladder complaints of painful urination
as well as cyclic urinary frequency and urgency may be
noted in affected women
Patient Symptoms

Defecatory Pain - reflects rectosigmoid involvement with

endometriotic implants. Symptoms may be chronic or cyclic, and
they may be associated with constipation, diarrhea, or cyclic
hematochezia
Noncyclical Pelvic Pain - approximately 40 to 60 percent of women
with chronic pelvic pain are found to have endometriosis at the time
of laparoscopy. If the rectovaginal septum or uterosacral ligaments
are involved with disease, pain may radiate to the rectum or lower
back. Alternatively, pain radiating down the leg and causing cyclic
sciatica may reflect posterior peritoneal endometriosis or direct
sciatic nerve involvement.
Infertility - may result from adhesions which are caused by
endometriosis and impair normal oocyte pick-up and transport by
the fallopian tube. Other defects include perturbations in ovarian
and immune function as well as implantation.
Patient Symptoms
Folliculogenesis and Embryogenesis Effects
 Embryo development and quality in women with endometriosis was
characterized by significantly fewer blastomeres per embryo and a
significantly greater rate of embryonic developmental arrest in the
endometriosis group
 This suggests a possible decreased developmental competence of
oocytes originating from the ovaries of women with endometriosis.
Another investigation found that oocyte number may be decreased
in women with endometriosis

Endometrical Changes

Intestinal Obstruction
Differential Diagnosis

 Gynecologic diseases - Tubo-ovarian

abscess,salpingitis,Endometritis, Hemorrhagic
ovarian cyst, Ovarian torsion, Primary
dysmenorrhea, Degenerating leiomyoma
 Nongynecologic diseases - Interstitial cystitis,
Chronic urinary tract infection, Renal calculi,
Inflammatory bowel disease, Irritable bowel
syndrome, Diverticulitis, Mesenteric
lymphadenitis, Musculoskeletal disorders
Diagnosis: Physical Examination

Visual Inspection

Speculum Examination - occasionally, bluish or red powder-burn lesions

may be seen on the cervix or the posterior fornix of the vagina.
Bimanual Examination - Uterosacral ligament nodularity and tenderness
may reflect active disease or scarring along the ligament; an enlarged
cystic adnexal mass may represent an ovarian endometrioma.
Diagnosis: Laboratory Testing

 Initially, a complete blood count (CBC), urinalysis and urine

cultures, vaginal cultures, and cervical swabs may be obtained to
exclude infections or sexually transmitted infections that may cause
pelvic inflammatory disease
 Serum CA125(cancer antigen 125) - in the diagnosis of
endometriosis revealed a sensitivity of only 28 percent and a
specificity of 90 percent. This marker appeares to be a better test in
diagnosing stage III and IV endometriosis.
 Other Serum Markers - Cancer antigen 19-9 (CA 19-9), Serum
placental protein 14; Interleukin-6 (IL-6) serum levels above 2
pg/mL (90-percent sensitivity and 67-percent specificity) and tumor
necrosis factor- (TNF- ) peritoneal fluid levels above 15 pg/mL
(100-percent sensitivity and 89-percent specificity) may be used.
Diagnostic Imaging: USG

 Endometriomas can be diagnosed by TVS (Trans Vaginal

Sonography) with adequate sensitivity in most settings if they are
20 mm in diameter or greater;
 Endometriomas often present as cystic structures with low-level
internal echoes, and occasional thick septations, thickened walls,
and echogenic wall foci

Ovarian endometrioma►

A cyst with diffuse internal

low-level echoes is seen

 Diagnosis: Magnetic Resonance
Imaging

 An endometrioma appears as a hyperintense mass on T1-

weighted sequences, with a tendency towards hypointensity in
T2-weighted sequences

T2- (A) and T1-weighted (B) images reveal

an endometrioma (arrows) just lateral to

the rectum
Diagnosis: Laparoscopy
 The primary method used for diagnosing endometriosis.
 Laparoscopic findings are variable and may include discrete
endometriotic lesions, endometrioma, and adhesion formation

Endometriotic Lesions - The appearance of these lesions by

laparoscopy is varied and colors may include red (red, red-pink, or
clear), white (white or yellow-brown), and black (black or black-
blue). Dark lesions are pigmented by hemosiderin deposition from
trapped menstrual debris. White and red lesions most commonly
correlate with the histologic findings of endometriosis.
endometriotic lesions may differ morphologically. They can appear
as smooth blebs on peritoneal surfaces, as holes or defects within
the peritoneum, or as flat stellate lesions whose points are formed
by surrounding scar tissue. Endometriotic lesions may be
superficial or may deeply invade the peritoneum or pelvic organs.
 Below the irrigator tip, a red and white
endometriotic lesion is seen on the pelvic
peritoneum during laparoscopy
Diagnosis: Laparoscopy

Endometriomas
 Endometriomas are cystic endometrial lesions contained within the
ovary
 They have the appearance of smooth-walled, brown cysts filled
with thick, chocolate-appearing liquid

A bisected endometrioma showing a shaggy

hemorrhagic lining ►
Diagnostic Algorithm

▲
Diagnosis Algorithm
Treatment
 Treatment for endometriosis depends on the woman's specific
symptoms, severity of symptoms, location of endometriotic
lesions, goals for treatment, and desire to conserve future fertility

Expectant Management
 for those with mild symptoms or for asymptomatic women
diagnosed incidentally, expectant management may be
appropriate

Medical Treatment of Endometriosis-Related Pain and Dysmenorrhea

1. Nonsteroidal Anti-Inflammatory Drugs - These agents
nonselectively inhibit the cyclooxygenase isoenzymes 1 and 2
(COX-1 and COX-2). These enzymes are responsible for the
synthesis of prostaglandins involved in the pain and inflammation
associated with endometriosis
Treatment

2. Combination Oral Contraceptives - These drugs appear to act

by inhibiting gonadotropin release, decreasing menstrual flow,
and decidualizing implants. These drugs can be used
conventionally in a cyclic regimen or may be used continuously,
without a break for withdrawal menses.
3. Progestins – they antagonize estrogenic effects on the
endometrium, causing initial decidualization and subsequent
endometrial atrophy.
4. Selective Progesterone Receptor Modulators (Mifepristone)
- These are progesterone-receptor ligands (molecules that bind
and activate or inactivate the progesterone receptor) and have
both progesterone antagonist and antagonist activities. It
reduces pelvic pain and extent of endometriosis, when used for
6 months at oral dosages of 50 mg daily.
Treatment
5. Androgens (Danazol, Gestrinone) - The predominant mechanism of
action appears to be suppression of midcycle luteinizing hormone (LH)
surge, creating a chronic anovulatory state. Danazol creates a
hypoestrogenic, hyperandrogenic state, inducing endometrial atrophy in
endometriotic implants. The recommended dosage of Danazol is 600 to
800 mg daily. Gestrinone predominantly induces a progesterone
withdrawal effect and decreases the number of estrogen and
progesterone receptors. Gestrinone is administered orally, 2.5 to 10 mg
weekly, given daily or three times weekly.

6. GnRH Agonists - Continuous, nonpulsatile GnRH administration results

in pituitary desensitization and subsequent loss of ovarian
steroidogenesis. With loss of ovarian estradiol production, the
hypoestrogenic environment removes the stimulation normally provided
to the endometriotic implants and creates a pseudomenopausal state
during treatment.
 Surgical Treatment of Endometriosis-
Related Pain

1. Lesion Removal and Adhesiolysis – done by laser ablation

or electrosurgical ablation.

2. Endometrioma Resection

3. Presacral Neurectomy - transection of presacral nerves lying

within the interiliac triangle may provide relief of chronic pelvic
pain.

4. Hysterectomy with Bilateral Oophorectomy - the definitive

and most effective therapy for women with endometriosis who
do not wish to retain their reproductive function. Limitations of
hysterectomy with bilateral oophorectomy include surgical
risks, pain recurrence, and the effects of hypoestrogenism.
 Treatment of Endometriosis-Related
Infertility

 Surgical ablation has been suggested to be

beneficial for women with infertility and minimal to
mild endometriosis
 Moderate to severe endometriosis may be treated
with surgery to restore normal anatomy and tubal
function.
 Patients with endometriosis and infertility are
candidates for fertility treatments such as controlled
ovarian hyperstimulation, intrauterine insemination,
and in vitro fertilization
THANK YOU ALL for your attention!
Have a nice day!