Uterine Leiomyoma Case File

Uterine Leiomyoma Case File

Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG

Case 11

A 37-year-old African American nulliparous woman complains of fatigue, loss of productivity, and regular heavy prolonged menses during the last 9 months, which worsens with time. She mentions that an asymptomatic myoma less than 4 cm was incidentally detected by transvaginal ultrasound examination during her annual visit to her gynecologist 1 year ago. She has always had normal Pap smear tests and she denies sexually transmitted diseases or abnormal mucopurulent vaginal discharge. Her pregnancy test is negative despite her wish to conceive during the last 12 months. Heart and lung examinations are normal. On examination, her blood pressure is 105/70 mm Hg, heart rate 98 beats/min, and temperature 97°F. On palpation, her abdomen presents a firm, round, nontender palpable midline mass 2 cm above the pubic symphysis. On bimanual examination, an anteverted, enlarged 15-week-size uterus is revealed

with a hard painless protruding fundal mass with irregular contour, approximately 7 cm in diameter that moves together with uterus during pushing the cervix upward or laterally. No adnexal masses are palpable. On speculum examination, no abnormalities are detected in the vagina and cervix. Transvaginal ultrasound examination demonstrates a solitary fundal intramural myoma protruding into the uterine cavity. Her hemoglobulin level is 8.1 g/dL, leukocyte count 10,500/mm3, and platelet count 160,000/mm3.

➤ What is the most likely diagnosis?

➤ What is your next step?

ANSWERS TO CASE 11:

Uterine Leiomyoma

Summary: An African American 37-year-old nulliparous woman, with a history of a known asymptomatic intramural leiomyoma less than 4 cm the last year, complains of menometrorrhagia. She has also been trying to become pregnant unsuccessfully for the last 12 months. Her pregnancy test is negative. On examination, a midline hard mass seems to be contiguous to an enlarged anteverted uterus with irregular contour. Also, she has anemia and mild tachycardia.

➤ Most likely diagnosis: Symptomatic uterine leiomyoma and infertility

➤ Next step: Ultrasound examination to confirm the clinical diagnosis, and then discussion with the patient about various options, including surgery including laparoscopic myomectomy

ANALYSIS

Objectives

1. Know that most myomas are asymptomatic and require intervention when they cause clinical symptoms.
2. Understand that the location and size of a myoma are the most crucial determinants of its potential to become symptomatic.
3. Know that the most common symptoms associated with uterine leiomyomas in reproductive age women are abnormal uterine bleeding manifested as menorrhagia or hypermenorrhea.
4. Describe the treatment options for uterine leiomyomata, including conservative, minimally invasive surgical procedures, medical therapies, and hysterectomy.

Considerations

This 37-year-old woman complains of fatigue, loss of productivity, and irregular menstrual pattern due to hypermenorrhea and menorrhagia. Clinical examination and history are consistent with a fundal myoma, because of the presence of a midline hard mass contiguous with the uterus that also explains its irregular contour. The prevalence of myomas in African American women is two to three times higher in comparison to white Caucasian women. Moreover, this uterine abnormal mass may be a possible cause of her infertility. The movement of this mass together with the uterus during lateral or upward displacement of cervix is another argument that this mass is of uterine origin. Furthermore, the absence of pelvic tenderness and fever with normal leukocyte count excludes pelvic inflammatory disease as a cause of abnormal uterine bleeding. The normal clinical findings on speculum examination and, also, the negative Pap smear tests make the diagnosis of vaginal or cervical pathology such as cervical or vaginal endometriosis, ectropion, cervical polyps, endometrial pedunculated myomas or polyps protruding through the external cervical os, cervical intraepithelial neoplasia, or malignancy remote. Dysfunctional uterine bleeding is excluded from the differential diagnosis, as it is frequent in adolescent and perimenopausal women and is a manifestation of anovulatory cycles in the absence of any uterine pathology or medical illness. Furthermore, in this case the patient seems to have ovulatory cycles because she has regular menses. Ectopic pregnancy as a cause of abnormal uterine bleeding is impossible due to her negative pregnancy test. Benign or malignant ovarian tumors are absent on bimanual examination. The clinical differential diagnosis between leiomyoma and adenomyoma as causes of menorrhagia is difficult without the use of transvaginal ultrasound or preferably magnetic resonance imaging (MRI) (ill-defined borders of the adenomyoma within myometrium in contrast to the pseudocapsule of myomas with clear contour). However, the main dominant symptom of adenomyoma or endometriosis is chronic pelvic pain and not menorrhagia that is the main complaint of women with symptomatic myomas. Adenomyosis is presented in the fourth or fifth decade of life and affects 1% of usually multiparous women. In general, endometrial sampling is performed with abnormal vaginal bleeding in women older than age 35 years. Finally, a Pipelle office endometrial biopsy is mandatory when the ultrasound findings raise the suspicion of endometrial hyperplasia or carcinoma, though they appear in peri- or postmenopausal women with metrorrhagia and not with menorrhagia. They are rarely found as a cause of abnormal uterine bleeding in women of reproductive age and especially younger than 40 years without the coexistence of risk factors such as excessive BMI, diabetes, or hypertension, which are not present in our case. Finally, the workup of menorrhagia except from platelet count should include further investigation of the thyroid function and clotting factors in order to exclude hyperthyroidism or coagulation disorders such as von Willebrand disease.

APPROACH TO

Uterine Leiomyoma

DEFINITIONS

HYPERMENORRHEA: It is defined as heavy, profuse periods that exceed 80 mL blood loss.

MENORRHAGIA: It is defined as heavy and prolonged periods that exceed 7 days.

METRORRHAGIA: It is defined as abnormal uterine bleeding at irregular intervals, particularly between the expected menstrual periods.

LEIOMYOMA: Benign smooth muscle tumor, which arises from the myometrium, also called myoma or fibroma. It is classified by its location in relation to the uterine wall: serosal (which may be broad-based or pedunculated), intramural, and submucosal. The latter is further distinguished as type 0 (pedunculated, totally protruding in the uterine cavity), type I (> 50% protrudes in the uterine cavity), and type II (< 50% protrudes in the uterine cavity or has an intramural portion of > 50%).

ADENOMYOSIS: It is the presence of heterotopic endometrial glands and stroma in the myometrium at least 2.5 mm below the endometrial-myometrial interface with adjacent smooth muscle hyperplasia. It can be either diffuse or focal, leading to the formation of the so-called “adenomyoma.”

ADENOMYOMA: It is a circumscribed nodule of hypertrophic and distorted endometrium and myometrium, which is usually embedded within the myometrium.

CLINICAL APPROACH

Uterine leiomyomas are among the most frequent pathologic entities encountered in gynecologic clinical practice. Myomas are the most common benign gynecologic neoplasms and the primary indication for hysterectomy, accounting for over 200,000 hysterectomies per year in the United States. Although in the pathology reports of hysterectomy specimens leiomyomas can be identified in up to 77%, they are clinically apparent in approximately 20% to 35% of women of reproductive age. Despite the high prevalence of these tumors, there is paucity of data available regarding the natural clinical history of myomas. They are monoclonal-independent lesions, such that multiple tumors from the uterus arise independently and may have distinct chromosomal abnormalities, while their growth is estrogen and progesterone dependent. Increased prevalence of leiomyomas is observed two- to threefold higher in African American women, who have earlier age at first diagnosis with multiple and larger myomas in comparison to that in white women. The prevalence of myomas increases with age until 50 years and then declines sharply. In pregnant women, the prevalence of myomas has been reported to be approximately 1.4%. Oral contraceptives, parity, and smoking decrease the risk of myoma development due to low oestrogen levels. On the other hand, obesity with higher oestrogen levels, diastolic hypertension with cytokine release, or injury of uterine smooth muscle as well as pelvic inflammatory disease with intrauterine irritation are associated with increased risk of fibroids. Malignant transformation of leiomyomas is extremely rare, and according to cytogenetic studies it has been documented that leiomyosarcomas arise de novo and rarely from a specific subset of myomas. However, the incidence of uterine sarcoma in symptomatic premenopausal women undergoing surgical removal is less than 0.3%. Current studies do not support any association between rapid growth of a leiomyoma and increased risk of malignancy. So, the rapid growth of an asymptomatic myoma that gains 6 weeks or more in gestational size within an interval of 1 year or less is an outdated indication for surgical intervention.

Most uterine myomas cause no symptoms. Approximately 62% of women with symptomatic myomas present with multiple symptoms, which correlate with their location, number, size, or concomitant degenerative changes. Excessive menstrual bleeding that leads to iron deficiency and subsequent anemia is the most common and often the sole symptom associated with myomas, particularly when there is protrusion in the endometrial cavity or distortion of it. Metrorrhagia, that is, alteration of the menstrual regularity, is not characteristic of myomas, and it should be worked up to exclude other pathologies. Pelvic pressure due to increased uterine size is responsible for the mass effect symptoms to the adjacent organs such as urinary frequency, urinary incontinence, hydronephrosis, constipation, tenesmus, infertility, and pregnancy complications (painful red degeneration, spontaneous miscarriage, and obstetric complications). Pelvic pain is attributed to degeneration changes or torsion of pedunculated myomas. Leiomyomas are considered to impair fertility by interference with sperm or embryo transport, causing anatomic distortion of the uterine cavity or cervix, by obstruction of tubal ostia, or by altering the uterine contractility and endometrial environment, but their precise role has not been clearly demonstrated.1

The gold standard for assessing the number, location, and size of uterine myomas is the transvaginal ultrasound. The combination of transvaginal and abdominal ultrasound is necessary for mapping myomas of an enlarged uterus with size greater than 10 weeks’ of gestation and especially for subserosal ones. Of course, its diagnostic accuracy for the detection of submucosal myomas and in the mapping of multiple ones is operator dependent and is enhanced by the addition of sonohysterography. Although MRI has the same accuracy in the detection of uterine myomas with ultrasound, it is much more expensive and it certainly consists of a reasonable disadvantage. However, MRI is a superior imaging technique in the mapping of multiple leiomyomas and in diagnostic differentiation from leiomyosarcomas or adenomyomas due to the precise depiction of well-defined pseudocapsule margins of benign myomas.2

The symptomatology of leiomyomas dictates the need and the urgency for medical or surgical intervention. But, regarding the impact of myomas on reproductive outcome, there are no definitive answers. However, submucosal and intramural leiomyomas distorting the uterine cavity and/or measuring larger than 5 to 7 cm seem to reduce pregnancy rates and pregnancy outcome and therefore they should be removed, especially if they are associated with multiple failed in vitro fertilization (IVF) cycles.

The target of medical treatment is to relieve the symptoms and regress the uterine or myoma volume by manipulating ovarian steroids due to its hormonal responsiveness. Gonadotropin-releasing hormone agonists (GnRH-a) are the most well-established agents for medical treatment of myomas, achieving temporary amenorrhoea and reduction in uterine or myoma size by 30% to 65% within 3 months of treatment. Add-back therapy, especially with raloxifene or tibolone, is necessary due to the significant side effects of hypoestrogenism caused by GnRH-a. However, prolonged use (6 months) should be avoided in premenopausal women, except in perimenopausal ones or in the preoperative period for the control of anemia. In addition, GnRH-a facilitate the ability to perform a hysterectomy laparoscopically or vaginally instead of abdominally, as well as permit a smaller or Pfannenstiel skin incision in a woman having an abdominal approach by reducing the size and vascularity of myomas. Exclusion criteria involve women with multiple small myomas that might subsequently be missed during myomectomy. Nonsteroidal anti-inflammatory agents and oral contraceptives with progestins only help to control the symptoms, without reducing the size of myomas or uterus. GnRH-antagonists, mifepristone, aromatase inhibitors, steroid receptor modulators, and levonorgestrel intrauterine device need further investigation before reaching definite conclusions about their effects on myomas.1,2

Although hysterectomy is considered the definitive treatment of uterine myomas, there is increasing demand for more conservative surgical approaches of myomas, which allow to preserve the uterus in situ. Abdominal myomectomy remains the treatment of choice for solitary myomas larger than 10 cm. When more than four multiple fibroids measuring greater than 7 cm are present, these must be removed if concomitant pathology that involves major surgery is encountered. Laparoscopic myomectomy compared with abdominal myomectomy has clear advantages in terms of postoperative pain relief, recovery time, hospital stay and demand for fewer transfusions, less postoperative fever, and de novo adhesion formation, but with no significant difference in terms of pregnancy and miscarriage rates in the few prospective, well-designed published studies. Of course, its application depends on gynecologist’s skills and mastering in endoscopic suturing, and also availability of the necessary instrumentation. Under these prerequisites, the need for conversion to laparotomy is reported only in 1.4% of cases.3,4,5

Adhesion formation can be eliminated by performing the incision (transverse incision is preferable to vertical in order to avoid incoming arcuate vessels, except from the corneal areas) on the anterior uterine wall or fundus in order to remove myomas, even if they are located posterior, by reducing the use of electrocautery and by using absorbable adhesion barriers. The risk of uterine rupture following myomectomy is ranged from 0.002% to 5% and usually occurs between 29 and 36 weeks’ of gestation. This is related to the following factors: (1) single instead of multilayer suturing, which minimizes the hematoma formation and maximizes the strength of uterine wall, (2) the excessive use of bipolar electrocoagulation for hemostasis that might impair the healing process, and (3) the poor suturing skills of the gynecologist to achieve uniform closure of the uterine defect by symmetric hickness of the scar in relation to the adjacent myometrium. Finally, hysteroscopic myomectomy is established as the gold standard for the treatment of submucosal myomas types 0 and I due to the advantage of no incision or suturing on the

Figure 11–1. A myomectomy is performed laparoscopically. The myoma is grasped with a corkscrew and dissected from the myometrium (A), and then the uterine defect is sutured closed (B).

normal myometrium (Figure 11–1). However, this approach can be rarely complicated by perforation, bleeding, infection, and intracavitary adhesion formation. Other techniques such as electromyolysis, uterine and ovarian artery ligation, or embolization have been proposed as conservative minimally invasive approaches with short-term results in women who desire to preserve their uterus, but with unknown effect on their fertility potential and risk of recurrence.

The recurrence of fibroids is diagnosed by ultrasound demonstrating myomas at least 2 cm in diameter. The 5-year risk of recurrence is 62% with a 9% risk of additional major surgery, a crucial issue when counselling patients for myomectomy. The majority of recurrences (75%) occur between 10 and 30 months after surgery. This risk is greater in patients with multiple myomas and large size of uterus. Moreover, the decreased tactile ability of laparoscopy may account for the increased rate of recurrence at laparoscopy.

Comprehension Questions

11.1 A 42-year-old woman is noted on pelvic examination to have an irregularly shaped mobile midline uterine mass. The gynecologist explains to the patient that this is likely to be uterine fibroids. The patient has no symptoms. Which of the following is the incidence rate of clinically apparent myomas?

A. 5%

B. 30%

C. 70%

D. 90%

11.2 Which type of myoma should be removed in infertile women to increase their pregnancy rates?

A. Submucosal

B. Intramural

C. Subserosal

D. Broad ligamental

11.3 To decrease the risk of adhesion formation with laparoscopic myomectomy, which one of the following incisions should be avoided?

A. Midline fundal

B. Anterior transverse

C. Anterior horizontal

D. Posterior

11.4 A gynecology case manager is reviewing charts for appropriate surgery. This month the focus is on myomectomy. Which of the following cases would most likely be flagged as an inappropriate indication for surgery?

A. Patient complains of pain

B. Patient complains of vaginal bleeding

C. Patient has pressure symptoms

D. Patient is informed that surgery would help protect against malignant transformation

ANSWERS

11.1 B. It is estimated that myomas are clinically apparent in approximately one out of every three or four women of the reproductive age. However, the prevalence of uterine myomas is higher in pathology reports of hysterectomy specimens.

11.2 A. Neither intramural nor subserosal myomas seem to affect fertility rates and removal has not been shown to increase fertility. Broad ligament myomas are outside the uterus.

11.3 D. Posterior uterine incision should be avoided, if possible, to decrease the risk of adhesion formation. The midline fundal incision has been popularized to decrease the risk of extending the uterine incision into the cornua. A horizontal incision has been advocated to avoid sectioning the blood vessels that run transversely to minimize blood loss.

11.4 D. Malignant transformation of uterine myomas is not acceptable indication for myomectomy in otherwise asymptomatic women. The risk of malignant transformation in an otherwise asymptomatic patient is less than 1:1000. However, if the uterus is noted to be growing in a postmenopausal woman, or uterine fibroids are noted in a patient with prior pelvic irradiation, surgery should be strongly considered.

Clinical Pearls

See Table 1-2 for definition of level of evidence and strength of recommendation

➤ Most myomas are asymptomatic common benign tumors of the myometrium with the highest incidence in women of reproductive age, affecting African American population three times as often as Caucasian women (Level A).

➤ The clinical suspicion of myomas can be confirmed by ultrasonography. MRI and sonohysterography are complementary diagnostic tools in complicated cases (Level A).

➤ Large intramural myomas (> 5 cm) and/or those distorting the endometrial cavity may adversely affect fertility (Level B).

➤ Medical treatment of myomas with GnRH-agonists is indicated for symptom relief during the preoperative period or in perimenopausal women (Level A).

➤ Laparoscopic myomectomy is a conservative surgical treatment in women who desire to preserve their uterus.However,hysterectomy is the definitive treatment of myomas (Level B).

REFERENCES

1. Arici A, Rayburn W. Myomas. In: Obstetrics and Gynecology Clinics of North America. Philadelphia, PA: Elsevier Saunders; 2006;33(1):1-225. 

2. Nowak R. Fibroids: pathophysiology and current medical treatment. Baillieres Best Pract Res Clin Obstet Gynaecol. 1999;13(2):223-238. 

3. Parker W. Laparoscopic myomectomy and abdominal myomectomy. Clin Obstet Gynecol. 2006;49(4):787-797. 

4. Carter JE, McCarus SD. Laparoscopic myomectomy. Time and cost analysis of power vs. manual morcellation. J Reprod Med. 1997 Jul;42(7):383-388. 

5. Alessandri F, Lijoi D, Mistrangelo E, et al. Randomized study of laparoscopic versus minilaparotomic myomectomy for uterine myomas. J Minim Invasive Gynecol. 2006 Mar-Apr;13:92-97. 

6. Walker C, Stewart E. Uterine fibroids: the elephant in the room. Science. 2005;308: 1589-1592. 

7. Hurst BS, Matthews ML, Marshburn PB. Laparoscopic myomectomy for symptomatic uterine myomas. Fertil Steril. 2005 Jan;83(1):1-23. 

8. Palomba S, Zupi E, Falbo, A, et al. A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: reproductive outcomes. Fertil Steri. 2007 Oct;88:933-941. 

9. Sinha R, Hegde A, Warty N, Patil N. Laparoscopic excision of very large myomas. J Am Assoc Gynecol Laparosc. Nov 2003;10(4):461-468. 

10. Parker W. Uterine myomas: management. Fertil Steril. 2007 Aug;88:255-271.

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