Uterine myomaand sarcoma

Fudan University

Weiwei Feng, MD,Ph.DEmail:jingsakura@gmail.com

Terms:

Myoma Leiomyoma

Fibroid

The commonest benign conditions of the uterus

Incidence• True incidence--- uncertain

• Common in women between 20~50y

• Clinically evident in 20%~30% of the women over 30 years old.

an exceedingly frequent event

Etiology

1.Related to hormones ( estrogen and progesterone)

2.Elevated ER expression in myoma

3.Abnormal cytogenetics

Arise during the period of menstrual activity, shrink after menopause

Classification

Subserosal (20%)

Intramural( 60~70%)

Submucosal (10~15%)

Corpus ( 90%) Cervix ( 10%)

Location

Growth pattern

Multiple (>=2)

Pathology- grossly examination

Pseudo capsule Margins : blunt, non-infiltrating, pushing

Cut surfaceWhorled,spiral patterns of fibers

Microscopic features

Elongated smooth muscle cells and fibrous tissue. No nuclear atypia, mitotic figures are absent or sparse.

Degenerations （变性）

Hyaline degeneration : commonest

Cystic degeneration

Red degeneration

Degeneration with calcification

Sarcomatous degeneration ( 0.4~0.8%)Malignant

Benign

Cause: gradually inadequacy of blood supply

Hyaline degeneration （透明样变）Cause: inadequacy of the blood supply

Uniform, eosinophilic (嗜伊红） , ground-glass appearance

Cystic degenration: secondly to hyaline degeneration

Red degeneration (红色变性）

Frequent during pregnancy or puerperium

A deep pink or red, softer

The ghosts of the muscle cells and their nuclear remain

Sarcomatous change（肉瘤样变）

1.Margin not well defined, blurred, merging, irregular2. Loss of whorled pattern3. Yellow, tan, or gray color

4. Heterogeneity5. Softer, less rubbery6. Absence of a bulging surface

Symptoms and physical signs

40~50% asymptomatic, discovered incidentally after routine examination

Menorrhagia (月经过多）

Menostaxis (经期延长）

Irregular mense

Intramural myoma

Anemia

Shortness of breathPalpitationsWeakness

Submucosal myoma

Change of mense

Pelvic mass and physical signs

Depend on the size, location, number and degeneration type

•Asymmetric enlargement of uterus

•Consistency Firm or rubbery Hard or stony ( calcification) Soft ( cystic)

Pelvic mass and Physical signs

•A firm mass extruded from the cervical OS (submucosal)

•Distortion and elongation of the cervical canal (cervical )

Compressive symptoms

NephrohydrosisHydroureter NephrohydrosisHydroureter

Frequency and retention of urine

Frequency and retention of urine

ConstipationDiscomfortConstipationDiscomfort

Different location of the myoma

Ureteralobstruction

Urethral obstruction

Recto-sigmoid compression

Cervical or lower segment

Cervical or broad ligment

Posterior

Increasing of discharge

Intramural myoma—increased uterus cavity area

Submucosal myoma— purulent discharge ( infection)

lower abdominal discomfort

PainRed degeneration

Torsion of pendunculated myoma

Extrusion of submucosal myoma from the cervix

Myoma and infertility

• infrequent primary cause of infertility

• 27% of women who received myomectomy had a history of infertility

• Usually caused by submucosal and intramural myoma

Myoma and pregnancy•Pregnancy loss , abortion

•Increased cesarean section ( Obstruction of labor) Question: Can myoma be removed during cesarean section?

•Postpartum hemorrhage

•Red degeneration

•Growth of myoma

•Most patients have uncomplicated pregnancies and deliveries.

Diagnostic methods1. History

2. Physical signs

3. Ultrasound/ MRI

4. Cervical cytology

5. Dilation &Curretage

4,5 : To rule out cervical cancer and endometrial cancer

6. Hysterosalpingography

7. Hysteroscopy

8. Laparoscopy

9. Other lab tests ( HCG, Hb)

Differential diagnosis

1. Pregnant uterus

2. Ovarian tumor

3. Uterine adenomyosis

4. Malignant uterine neoplasms

Pregnant uterus VS. Myoma Pregnant uterus

Myoma

History Amenorrhoea Regular period, menorrhagia

Signs Symmetric enlarged uterus

Asymmetric enlarged uterus

Ultra-sound

Sac or fetus in cavity

Low-echoed mass

Lab. test HCG + HCG -

Ovarian tumor VS. MyomaSolid ovarian tumor VS. Subserous leiomyoma

Ovarian cyst VS. Cystic /hyaline degenerative myoma

Adenomyosis VS. Myoma

adenomyosis leiomyoma

Endometrial cancer / Cervical Cancer VS. Submucous myoma

Endometrial cancer Cervical cancer Submucous myoma

Management

principle

Factors should be taken into consideration

• Age• Desire of childbearing • Symptoms• Location, size and number • Malignant change

observation• Observation with close follow-up Indications: small and asymptomatic myoma

especially for peri-menopausal women

Medications

Indications:

Size <= 2 months pregnant uterusMild symptomsPeri-menopausal With contraindications for operation

Gonadotropin-releasing hormone agonist (GnRH-a)

Mechanism: Inhibit FSH, LH and Estrogen

Efficacy : 40~60% decrease in uterine volumeSide effects: hypoestrogenism reversible bone loss and hot flashes obvious for long use (>6 months) estrogen add-back therapy Regrowth : within a few months after stopping therapy.

Indications of GnRH-a

1. Preservation of fertility before attempting conception

2. Treatment of anemia to allow recovery of Hb before surgery, minimizing the need for blood transfusion

3. Preoperative treatment of large leiomyomas to make surgery more feasible.

4. Treatment of women in menopausal period

• GnRH-a gesorelin ( 3.6mg q28d× 6) , leuprorelin: ( 3.75mg q28d × 6)

• Mifepristone ( Ru486) : 12.5mg P.O. progesterone receptor antagonist

Indications:

1. Menorrhagia with anemia, resistant to medication

2. Markedly enlarged uterus with compression symptoms

3. Chronic pain, dyspareunia, Acute pain, as in torsion of a pedunculated myoma, or

prolapsing submucosal fibroid

4. Rapid enlargement of uterus-sarcomatous change?

5. Infertility or spontaneous abortion with myoma as the only abnormal finding

Surgery

Surgical procedures

Myomectomy

Hysterectomy

Abdominal / laparoscopic / hysteroscopic or vaginal

• Myomectomy Indications: young patients who desire for childbearing Recurrence risk: as high as 50%, and up to 1/3 requiring repeat surgery

Hysterectomy Indications: no requirement of uterine preservation Note: : Cervical or endometrial cancer must be excluded before

operation

Other treatments:

Uterine artery embolization, UAE

Endometrium ablation by hysteroscopy

Video 1: Laparoscopic myomectomy

Advantages : Minimizes incision, quicker recovery

Disadvantages: Risks of convertion to a laparotomy Immature suture technique: uterine rupture during pregnancy

Video 2: Laparoscopic hysterectomy

Uterine sarcoma

General informationRare tumors of mesodermal origin (myometrium, connective tissue, stroma of endometrium, or secondly to myoma)

2~4% of uterine malignancies

Poor prognosis ( death occurring within 1 to 2 years after diagnosis, except ESS)

Leiomyosarcoma (~45%)

Endometrial stromal sarcoma (ESS) Undifferentiated endometrial sarcoma (15~25%)

Mixed epithelial and mesenchymal tumors Adenosarcoma Carcinosarcoma , or malignant mesodermal mixed tumor, MMMT

Three commonest types

leiomyosarcoma(平滑肌肉瘤）• Age: 45-55 yr, • Usually arise de novo from uterine smooth muscle,

rarely arise in a preexisting myoma • Diagnosis usually is not made before surgery. D&C

are diagnostic only for ~10% of tumors that are submucous.

• Poor prognosis

leiomyosarcoma

mitotic figures>5/10HPF severe cytologic atypia coagulative tumor necrosis

Endometrial stromal sarcoma • Before 2003, low grade ESS, low grade (低度恶性子宫内膜间质肉瘤） Most ESS involve endometrium, infiltrate muscles, sometimes protrude from the OS.

D&C lead to diagnosis (about half).

The only uterine sarcoma related to hormone, ER, PR (+), response to hormone treatment

Behaviour : indolent, late recurrence and metastasis may occur. 5-yr survival >80%

ESS, low grade

ESS with invasive borderOriginated from endometrial stromal cells, similar to proliferative phase

• Undifferentiated endometrial sarcoma ( UES)未分化子宫肉瘤）

UES: behave aggressively, with 5-year survival < 40%

UES with severe atypiaMitosis>10/10HPF

Mixed epithelial and mesenchymal tumors

• Adenosarcoma :

Benign epithelial element Malignant mesenchymal element

• Carcinosarcoma (癌肉瘤） Malignant mesodermal mixed tumor, MMMT

Both epithelial and mesenchymal elements are malignant

In FIGO 2009, carcinosarcoma was regarded as type II endometrial carcinoma, because the prognosis is mainly determined by epithelial elements.

• most patients being postmenopausal

• Enlarged or irregular uterus Tumor protrudes through the cervical OS like a polyp (50%)

• Behaviour: aggressive Recurrence rate: 53% 5 year survival 11~35%

Carcinosarcoma

Patterns of spread

• Directly spread (to myometrium, pelvic structures) • pelvic vessels• lymphatics

Symptoms and signs

• Uterine Bleeding ( 75%~95%)

• Pelvic pain (33%)

• Pelvic mass

Enlarged uterus ( 15%~50%)

Prolapsed necrotic tissue through cervical OS

• Other :

Compressive symptoms

Discharge

Diagnosis

Symptoms ( Uterine bleeding ) and signs

Ultrasound / MRI D & C

Pathological diagnosis

Staging

New staging systems ( FIGO 2009)

Three different staging systems for 1. Leiomyosarcoma 2. ESS and adenosarcoma 3. Carcinosarcoma

Staging FIGO 2009 leiomyosarcoma

• I Tumor limited to uterus IA<5CM

IB ≥ 5CM• II Tumor grows outside of uterus but not outside the pelvis IIA tumor is growing into adnexa IIB tumor is growing to the tissue of pelvis other than adnexa

• III tumor grows into tissue of abdomen ( not just intruding into abdomen) IIIA in one place IIIB in 2 or more places IIIC tumor has spread to pelvic/ para-aortic lymph nodes

• IV The tumorr has spread to the urinary bladder or the rectum, and/or to distant organs, such as the bones or lung

IVA spread to bladder or the rectum IVB distant metastasis

Staging FIGO 2009 ESS and adenosarcoma

• I Tumor limited to uterus IA limited to endometrium

IB <1/2 myometrium IC ≥ 1/2 myometrium

• II Tumor grows outside of uterus but not outside the pelvis IIA tumor is growing into adnexa IIB tumor is growing to the tissue of pelvis other than adnexa

• III tumor grows into tissue of abdomen ( not just intruding into abdomen) IIIA in one place IIIB in 2 or more places IIIC tumor has spread to pelvic/ parpaotic lymphnodes

• IV The tumor has spread to the urinary bladder or the rectum, and/or to distant organs, such as the bones or lung

IVA spread to bladder or the rectum IVB distant metastasis

Carcinosarcoma

the same as FIGO Staging for endometrial cancer

Treatment 1. Surgery: only treatment of proven curative value

Stage I and II : hysterectomy + bilateral oorphorectomy

Pelvic and or para-aortic lymphnectomy: ESS/UES and Carcinosarcoma: required Leiomyosarcoma: not certain

• cytoreductive surgery for advanced stage ( III or IV) patients

2. Adjunvant therapy: Chemotherapy +/- radiotherapy

Radiotherapy improves tumor control in the pelvis without influencing final outcome

chemotherapy : response rate (~20%) Drugs: doxorubicin, cisplatin, ifosfamide, palitaxel

3. Hormone therapy ( only used in ESS, low grade)

progesterone, letrozol GnRH antagonist

Prognosis

Generally poor, 5-year survival 20%~30% Stage is the most important prognostic factor.

Cell type, grade, metastasis, and treatment

• If the leiomyosarcoma arises in a benign myoma, the prognosis is improved

• ESS: 5-yr survival >80%.

Case discussion

History : A 33 year old woman complains heavy bleeding during period for 1 year. The duration of bleeding usually lasts 9 days. Sometimes she has blotting.

Physical examination : shows pale and short of breath. Pelvic examination revealed enlarged uterus with a size of two-month pregnancy.

Case discussion

Ultrasound: A 65/55/50 mm low-echoes mass with clear margin in myometrium was seen by ultrasound. In addition, a 23/20/19mm low echoes mass protrudes from uterus cavity.

Lab test: Hb: 80g/L.

Questions

•What ‘s the diagnosis ? ( give the evidence)

•Which diseases should be excluded?

•What is the suitable treatment?

•Does this treatment affect fertility?

Take home message

About the myoma

•The symptoms are related to the types of location and degenerations. Half of the patients are asymptomatic. The commonest symptom is change of mense.

•Ultrasound is the common and accurate diagnostic tool.

Take home message

About the myoma

•No treatment is required for asymptomatic patients. Medications are suitable for peri-menopausal patients with mild symptoms.

•Surgery is the effective way to treat symptomatic patients or suspicious for sarcomatous change.

Take home message

About the sarcoma

•Rare tumors with poor prognosis

•The commonest symptom is irregular vaginal bleeding with pain. Diagnosis is by pathology results.

•Surgical treatment is the main option. Adjunvant therapy depends on stage and type.