Case 41. Uterine Leiomyomata

 A 40-year-old G5P5 woman complains of heavy vaginal bleeding with clots of

2-year duration. She denies bleeding or spotting between periods. She states

that several years ago a doctor had told her that her uterus was enlarged. Her

records indicate that 1 year ago she underwent a uterine dilation and curettage, with the tissue showing benign pathology. She denies fatigue, cold

intolerance, or galactorrhea. She takes ibuprofen without relief of her vaginal

bleeding. On examination, her blood pressure (BP) is 135/80 mm Hg, heart

rate (HR) is 80 beats per minute (bpm), weight is 140 lb, and temperature

is 98°F (36.6°C). The heart and lung examinations are normal. The abdomen

reveals a lower abdominal midline irregular mass. On pelvic examination,

the cervix is anteriorly displaced. An irregular midline mass approximately 18

weeks’ size seems to move in conjunction with the cervix. No adnexal masses

are palpated. Her pregnancy test is negative. Her hemoglobin level is 9.0 g/dL,

leukocyte count is 6,000/mm3, and platelet count is 160,000/mm3.

» What is the most likely diagnosis?

» What is your next step?

CASE 41

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ANSWERS TO CASE 41:

Uterine Leiomyomata

Summary: A 40-year-old G5P5 woman with a history of an enlarged uterus complains of menorrhagia and anemia despite ibuprofen. A prior uterine dilation and

curettage showed benign pathology. Examination reveals an irregular midline mass

approximately 18 weeks’ size that is seemingly contiguous with the cervix, and

there is an anteriorly displaced cervix.

 Most likely diagnosis: Symptomatic uterine leiomyomata.

 Next step: Offer the patient a hysterectomy.

ANALYSIS

Objectives

1. Understand that the most common reason for hysterectomy in the United States

is symptomatic uterine fibroids.

2. Know that hysterectomy is generally reserved for women with symptomatic

uterine fibroids that are refractory to an adequate trial of medical therapy.

3. Know that menorrhagia is the most common symptom of uterine leiomyomata.

Considerations

This 40-year-old woman complains of menorrhagia. The physical examination is

consistent with uterine fibroids, because of the enlarged midline mass that is irregular and contiguous with the cervix. If the mass were lateral or moved apart from

the cervix, another type of pelvic mass, such as ovarian, would be suspected. This

patient complains of menorrhagia (excessive bleeding during menses), the most

common symptom of uterine fibroids. If she had intermenstrual bleeding, the clinician would have to consider other diseases, such as endometrial hyperplasia, endometrial polyp, or uterine cancer, in addition to the uterine leiomyomata. Irregular

cycles (menometrorrhagia) may suggest an anovulatory process. The patient has

anemia despite medical therapy, constituting the indication for intervention, such

as hysterectomy. If the uterus were smaller, consideration may be given toward

another medical agent, such as medroxyprogesterone acetate (Provera). Also,

a gonadotropin-releasing hormone (GnRH ) agonist can be used to shrink the

fibroids temporarily, to correct the anemia, or make the surgery easier. The maximum shrinkage of fibroids is usually seen after 3 months of GnRH agonist therapy.

After the GnRH agonist is stopped, the fibroids would regrow.

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APPROACH TO:

Suspected Uterine Leiomyomata

DEFINITIONS

LEIOMYOMATA: Benign, smooth muscle tumors, usually of the uterus.

LEIOMYOSARCOMA: Malignant, smooth muscle tumor, with numerous mitoses.

SUBMUCOSAL FIBROID: Leiomyomata that are primarily on the endometrial

side of the uterus and protrude into the uterine cavity (Figure 41– 1).

INTRAMURAL FIBROID:Leiomyomata that are primarily in the uterine muscle.

SUBSEROSAL FIBROID: Leiomyomata that are primarily on the outside of

the uterus, on the serosal surface. Physical examination may reveal a “knobby”

sensation.

PEDUNCULATED FIBROID: Leiomyoma that is on a stalk.

CARNEOUS DEGENERATION: Changes of the leiomyomata due to rapid

growth; the center of the fibroid becomes red, causing pain. This is synonymous

with red degeneration.

Figure 41–1. Uterine leiomyomata. Various uterine leiomyomata are depicted based on their location in the uterus.

Pedunculated

Subserosal

Cervical

Submucosal

Intramural

Prolapsed

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CLINICAL APPROACH

Evaluation

Uterine leiomyomata are the most common tumors of the pelvis and the leading indication for hysterectomy in the United States. They occur in up to 25%

of women, and have a variety of clinical presentations. The most common clinical manifestation is menorrhagia, or excessive bleeding during menses. The exact

mechanism is unclear and may be due to an increased endometrial surface area or

the disruption of hemostatic mechanisms during menses by the fibroids. Another

speculated explanation is ulceration of the submucosal fibroid surfaces.

Many uterine fibroids are asymptomatic and only need to be monitored. Very

rarely, uterine leiomyomata degenerate into leiomyosarcoma. Some signs of this

process include rapid growth, such as an increase of more than 6 weeks’ gestational

size in 1 year. A history of radiation to the pelvis is a risk factor.

If the uterine leiomyomata are sufficiently large, patients may also complain of

pressure to the pelvis, bladder, or rectum. Rarely, the uterine fibroid on a pedicle

may twist, leading to necrosis and pain. Also, a submucous leiomyomata can prolapse through the cervix, leading to labor-like uterine contraction pain.

The physical examination typical of uterine leiomyomata is an irregular, midline,

firm, nontender mass that moves contiguously with the cervix. This presentation

is approximately 95% accurate. Most of the time, ultrasound examination is performed to confirm the diagnosis. Lateral, fixed, or fluctuant masses are not typical

for fibroids. The differential diagnosis includes ovarian masses, tubo-ovarian masses,

pelvic kidney, and endometrioma. Significant menorrhagia often leads to anemia.

Treatment

The initial treatment of uterine fibroids is pharmacological, such as with nonsteroidal anti-inflammatory agents or progestin therapy. Gonadotropin-releasing

hormone agonists lead to a decrease in uterine fibroid size, reaching its maximal

effect in 3 months. After the discontinuation of this agent, the leiomyomata usually regrow to the pretreatment size. Thus, GnRH agonist therapy is reserved for

tumor shrinkage or correction of anemia prior to operative treatment. Other treatments include the levonorgestrel intrauterine device (IUD), selective progesterone

receptor antagonists, or oral contraceptives. Notably, the levonorgestrel IUD can be

used for women with uterine fibroids without marked distortion of the uterine cavity. With intracavitary (submucosal) uterine fibroids, hysteroscopic resection is the

best conservative treatment option.

Hysterectomy is considered the proven treatment for symptomatic uterine

fibroids when future pregnancy is undesired. The indication for surgery is persistent symptoms despite medical therapy. Myomectomy is still considered the procedure of choice for women with symptomatic uterine leiomyomata who desire

pregnancy. One in four women who undergo myomectomy will require a hysterectomy in the following 20 years. Myomectomy can be accomplished through several

approaches including hysteroscopic, open abdominal, laparoscopic and robotically.

Advantages to robotic-assisted laparoscopic myomectomy include decreased intraoperative blood loss, shorter hospital stays; however, the technique incurs higher

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cost and greater intraoperative time. Myomectomy is not indicated in women who

have uterine fibroids unless there have been pregnancy complications due to uterine fibroids in the past.

Uterine artery embolization is a technique performed by cannulizing the femoral artery and catheterizing both uterine arteries directly, and infusing embolization particles that preferentially float to the fibroid vessels. Fibroid infarction and

subsequent hyalinization and fibrosis result. Short-term results appear promising;

initial studies with follow-up over 5 years show symptom relief for approximately

75% of patients. This intervention should not be used in women who want to get

pregnant in the future since there is an increased risk of placentation abnormalities.

Very large uteri (> 20 weeks size) or very large fibroids may not respond as well;

also, submucosal fibroids may cause bleeding, pain, cramping, and expulsion which

can be unpleasant for the patient. Pregnancy, a suspected gynecologic malignancy,

history of PID, or renal failure are contraindications to the procedure.

Recent Advances

In 2014, the FDA issued a warning on the use of laparoscopic power morcellation

during hysterectomy or myomectomy for women with suspected uterine fibroids

due to the concerns of undiagnosed uterine leiomyosarcoma. This was due to concerns raised by the case of an unsuspected Boston anesthesiologist who underwent

laparoscopic power morcellation for suspected fibroids. The risk calculated by the

FDA was 1:350 cases, and that the power morcellation would spread the malignant

cells in the peritoneal cavity and worsen the prognosis. Various hospitals and physicians have taken different approaches to this FDA warning; however, the use of

laparoscopic power morcellation has been dramatically reduced.

COMPREHENSION QUESTIONS

41.1 A 29-year-old woman is noted to have three consecutive first-trimester spontaneous abortions. After an evaluation for the recurrent abortions including

karyotype of the parents, hysterosalpingogram, vaginal sonogram, and testing for antiphospholipid syndrome, the obstetrician concludes the uterine

fibroids are the etiology. Which of the following types of uterine fibroids

would most likely lead to recurrent abortion?

A. Submucosal

B. Intramural

C. Subserosal

D. Parasitic

E. Pedunculated

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41.2 A 39-year-old woman is diagnosed as having probable uterine fibroids based

on a pelvic examination revealing an enlarged irregular uterus. She is currently asymptomatic and expressed surprise that she had “growths” of the

uterus. If she were to develop symptoms, which of the following would be the

most common manifestation?

A. Infertility

B. Menorrhagia

C. Ureteral obstruction

D. Pelvic pain

E. Recurrent abortion

41.3 A 29-year-old G2P1 woman at 39 weeks’ gestation had a myomectomy for

infertility previously. While pushing during the second stage of labor, she is

noted to have fetal bradycardia associated with some vaginal bleeding. The

fetal head, which was previously at + 2 station, is now noted to be at – 3 station. Which of the following is the most likely diagnosis?

A. Submucosal myomata

B. Umbilical cord prolapse

C. Uterine rupture

D. Placental abruption

E. Fetal congenital heart block

41.4 A 65-year-old woman is noted to have suspected uterine fibroids on physical

examination. Over the course of 1 year, she is noted to have enlargement of

her uterus from approximately 12 weeks’ size to 20 weeks’ size. Which of the

following is the best management?

A. Continued careful observation

B. Monitoring with ultrasound examinations

C. Exploratory laparotomy with hysterectomy

D. Gonadotropin-releasing hormone agonist

E. Progestin therapy

41.5 A 38-year-old woman is diagnosed with uterine fibroids of approximately

18 weeks’ size and irregular in contour. She has significant menorrhagia with

symptomatic anemia. The patient has finished her childbearing, but adamantly refuses surgical management for her fibroids. Which of the following

is the best management for this patient?

A. Endometrial ablation procedure

B. Intramuscular GnRH agonist therapy

C. Levonorgestrel IUD

D. Oral contraceptive therapy

E. Uterine artery embolization

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41.6. A 45-year-old G2P2 woman has significant heavy menstrual bleeding due to

uterine fibroids. The pelvic ultrasound shows two large uterine fibroids—

one in the anterior corpus and one in the uterine fundal region. The patient

is considering uterine artery embolization. Which of the following is the best

way to ensure that the uterine fibroids are not leiomyosarcoma?

A. Endometrial biopsy

B. Uterine dilatation and curettage

C. Percutaneous biopsy of the fibroid

D. Magnetic resonance imaging

E. Serum markers for CA125 and CEA

ANSWERS

41.1 A. Submucousal fibroids are the fibroids most likely to be associated with

recurrent abortion because of their effect on the uterine cavity. The contours

of the endometrium are altered and therefore, less favorable for implantation.

There may be insufficient vasculature to provide adequate blood supply to

the growing embryo if it were to implant along the side of the endometrium

containing a submucosal fibroid. In the second trimester of pregnancy, the

other answer choices are not associated with an increased risk of recurrent

abortion because they do not alter the integrity of the endometrium.

41.2 B. Menorrhagia is the most common symptom of uterine fibroids, and

severe menorrhagia often leads to anemia. Infertility and recurrent abortion

may occur with submucosal fibroids due to the effects on the uterine cavity,

whereas impingement on the ureters is most likely to occur with subserosal fibroids, but these are much less common than menorrhagia. Pelvic pain

is not very common, and many uterine fibroids are asymptomatic and only

require monitoring. If the uterine leiomyomata are large enough, patients

may complain of pressure to the pelvis, bladder, or rectum. Though rare, a

uterine fibroid on a pedicle may twist, leading to necrosis and severe pain.

41.3 C. Extensive myomectomies sometimes necessitate cesarean delivery

because of the risk of uterine rupture. Most practitioners use the rule of

thumb that if the endometrial cavity is entered during myomectomy, a

cesarean delivery should be performed with pregnancy. As with uterine

rupture, fetal bradycardia may also occur if the umbilical cord becomes prolapsed, but cord prolapse is not a risk factor from having a myomectomy.

A submucosalmyomata is related to problems with fertility and implantation of the embryo, not problems during labor such as uterine rupture.

Placental abruption is not associated with fetal bradycardia or as a risk after

myomectomy. Myomectomies do not cause congenital anomalies or disease

processes to occur in a developing fetus.

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41.4 C. The rapid growth of the uterus suggests leiomyosarcoma; the diagnosis

and treatment are surgical, especially in a woman of nonchildbearing age.

Also, substantial growth of uterine fibroids in postmenopausal women is

unusual due to the lower estrogen levels. In other words, uterine fibroids

typically grow in response to estrogen. Once a fibroid degenerates into cancer, progestin therapy and gonadotropin-releasing hormone agonists have no

more effect on the tumor and are no longer treatment options for shrinking

the mass.

41.5 E. For a relatively large uterus due to fibroids, uterine artery embolization is

the best alternative therapy to surgery. The majority of patients treated with

this modality will have improvement. The IUD would likely not stay in place

with an irregular uterine cavity; endometrial ablation is technically difficult

if not impossible with a large irregular uterine cavity. GnRH agonist is useful in the short term (3-6 months) and is effective in shrinking the fibroids

and slowing the bleeding; but its use is limited to 6 months due to the risk of

osteoporosis.

41.6 C. Although rare, leiomyosarcoma does occur and can be very difficult if not

impossible to distinguish from a uterine fibroid. MR imaging usually reveals a

large heterogenous mass in the uterus with areas of both hyper- and hypoenhancement; however, there is considerable overlap between leiomyosarcoma

and benign leiomyomata. Thus, percutaneous biopsy or even better surgical

resection and pathological examination are the best ways to assess for leiomyosarcoma. Endometrial biopsy and uterine D&C are usually not helpful to

evaluate for leiomyosarcoma.

CLINICAL PEARLS

» The most common reason for hysterectomy is symptomatic uterine

fibroids.

» The most common symptom of uterine fibroids is menorrhagia, heavy

bleeding during menses.

» The physical examination consistent with uterine leiomyomata is an

irregular pelvic mass that is mobile, midline, and moves contiguously

with the cervix.

» Leiomyosarcoma rarely arises from leiomyoma; rapid growth or a history

of prior pelvic irradiation should raise the index of suspicion.

» Significant growth in suspected uterine fibroids in a postmenopausal

woman is unusual and generally requires surgical evaluation.

» Asymptomatic uterine fibroids require surgical intervention in the presence of unexplained rapid growth, ureteral obstruction, or the inability to

differentiate the fibroid from other types of pelvic masses.

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REFERENCES

American College of Obstetricians and Gynecologists. Alternatives to hysterectomy in the management

of leiomyomata. ACOG Practice Bulletin 96. Washington, DC; 2008. (Reaffirmed 2014.)

Barakat EE, Bedaiwy MA, Z imberg S, Nutter B, Nosseir M, Flacone T. Robotic-assisted, laparoscopic, and abdominal myomectomy: a comparison of surgical outcomes. Obstet Gynecol. 2011;117:

256-266.

FDA Safety Communication. FDA discourages use of laparoscopic power morcellation for removal

of uterus or uterine fibroids. http:/ / www.fda.gov/ NewsEvents/ Newsroom/ PressAnnouncements/

ucm393689.htm; Accessed 20.09.2015.

Katz VL. Benign gynecologic lesions. In: Lentz GM, Lobo RA, Gersenson DM, Katz VL, eds. Comprehensive Gynecology. 6th ed. St. Louis, MO: Mosby-Year Book; 2012:419-470.

Nelson AL, Gambone JC. Congenital anomalies and benign conditions of the uterine corpus and

cervix. In: H acker N F, Gambone JC, H obel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed.

Philadelphia, PA: Saunders; 2009:240-247.

Spies JB, Bruno J, Czeyda-Pommersheim F, Magee ST, Ascher SA, Jha RC. Long-term outcome of

uterine artery embolization of leiomyomata. Obstet Gynecol. 2005;106:933.

Steward EA. Uterine fibroids. New Engl J Med. 2015;372:1646-1655.

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