1. Uterine myoma and sarcoma Fudan University Weiwei Feng, MD,Ph
Uterine myoma and sarcoma Fudan University Weiwei Feng, MD,Ph.D

3. Terms:
Myoma
Leiomyoma
Fibroid
The commonest benign conditions of the uterus

4. an exceedingly frequent event
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

5. Etiology Related to hormones ( estrogen and progesterone)
Elevated ER expression in myoma
Abnormal cytogenetics
Arise during the period of menstrual activity, shrink after menopause

6. Classification Location Corpus ( 90%) Cervix ( 10%) Growth pattern
Intramural( 60~70%)
Subserosal (20%)
Submucosal (10~15%)
Multiple (>=2)

7. Pathology- grossly examination
Pseudo capsule
Margins : blunt,
non-infiltrating,
pushing
Cut surface
Whorled,
spiral patterns of fibers

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

9. Sarcomatous degeneration ( 0.4~0.8%)
Degenerations
Cause: gradually inadequacy of blood supply
Hyaline degeneration : commonest
Cystic degeneration
Red degeneration
Degeneration with calcification
Benign
Malignant
Sarcomatous degeneration ( 0.4~0.8%)

10. Hyaline degeneration Cause: inadequacy of the blood supply
Uniform, eosinophilic, ground-glass appearance
Cystic degenration: secondly to hyaline degeneration

11. Red degeneration Frequent during pregnancy or puerperium
A deep pink or red, softer
The ghosts of the muscle
cells and their
nuclear remain

12. Sarcomatous change 1.Margin not well defined,
blurred, merging, irregular
2. Loss of whorled pattern
3. Yellow, tan, or gray color
4. Heterogeneity
5. Softer, less rubbery
6. Absence of a bulging
surface

13. Symptoms and physical signs
40~50% asymptomatic, discovered incidentally after routine examination

14. Menorrhagia Menostaxis Irregular mense
Change of mense
Menorrhagia Menostaxis Irregular mense
Intramural myoma
Anemia
Shortness of breath
Palpitations
Weakness
Submucosal myoma

15. 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)

16. Pelvic mass and Physical signs
A firm mass extruded from the
cervical OS (submucosal)
Distortion and elongation of
the cervical canal (cervical )

17. Compressive symptoms Different location of the myoma Cervical or
lower segment
Cervical or
broad ligment
Posterior
Urethral obstruction
Ureteral
obstruction
Recto-sigmoid
compression
Frequency and retention of urine
Nephrohydrosis
Hydroureter
Constipation
Discomfort

19. Increasing of discharge
Intramural myoma—increased uterus cavity area
Submucosal myoma— purulent discharge ( infection)
lower abdominal discomfort

20. Pain Red degeneration Torsion of pendunculated myoma
Extrusion of submucosal myoma from the cervix

21. 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

22. 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.

23. Diagnostic methods History Physical signs Ultrasound/ MRI
4. Cervical cytology
5. Dilation &Curretage
4,5 : To rule out cervical cancer and endometrial cancer 23

24. 6. Hysterosalpingography
7. Hysteroscopy
8. Laparoscopy
9. Other lab tests ( HCG, Hb)

25. Differential diagnosis
Pregnant uterus
Ovarian tumor
Uterine adenomyosis
Malignant uterine neoplasms

26. Pregnant uterus VS. 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 -

27. Ovarian tumor VS. Myoma Solid ovarian tumor VS. Subserous leiomyoma
Ovarian cyst VS. Cystic /hyaline degenerative myoma

28. Adenomyosis VS. Myoma
adenomyosis
leiomyoma

29. Endometrial cancer / Cervical Cancer VS. Submucous myoma

30. Management

31. principle Factors should be taken into consideration Age
Desire of childbearing
Symptoms
Location, size and number
Malignant change

32. observation Observation with close follow-up
Indications: small and asymptomatic myoma especially for peri-menopausal women

33. Medications Indications:
Size <= 2 months pregnant uterus Mild symptoms Peri-menopausal With contraindications for operation

34. Gonadotropin-releasing hormone agonist (GnRH-a)
Mechanism: Inhibit FSH, LH and Estrogen Efficacy : 40~60% decrease in uterine volume Side 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. .

35. Indications of GnRH-a
Preservation of fertility before attempting conception
Treatment of anemia to allow recovery of Hb before surgery, minimizing the need for blood transfusion
Preoperative treatment of large leiomyomas to make surgery more feasible.
Treatment of women in menopausal period .

36. GnRH-a
gesorelin ( 3.6mg q28d× 6) ,
leuprorelin: ( 3.75mg q28d × 6)
Mifepristone ( Ru486) : 12.5mg P.O.
progesterone receptor antagonist

37. Surgery Indications: Menorrhagia with anemia, resistant to medication
Markedly enlarged uterus with compression symptoms
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

38. Surgical procedures Myomectomy Hysterectomy
Abdominal / laparoscopic / hysteroscopic or vaginal
Myomectomy
Hysterectomy 38

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

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

41. Other treatments: Uterine artery embolization, UAE
Endometrium ablation by hysteroscopy

42. 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

43. Uterine sarcoma

44. General information
Rare 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)

45. Three commonest types Leiomyosarcoma (~45%)
Endometrial stromal sarcoma (ESS) Undifferentiated endometrial sarcoma (15~25%)
Mixed epithelial and mesenchymal tumors
Adenosarcoma
Carcinosarcoma , or malignant mesodermal mixed tumor, MMMT

46. leiomyosarcoma 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

47. leiomyosarcoma mitotic figures>5/10HPF severe cytologic atypia,
mitotic figures>5/10HPF
severe cytologic atypia
coagulative tumor necrosis

48. 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%

49. ESS, low grade Originated from endometrial stromal cells,
similar to proliferative phase
ESS with invasive border

50. Undifferentiated endometrial sarcoma ( UES) UES: behave aggressively,
with 5-year survival < 40%
UES with severe atypia
Mitosis>10/10HPF

51. Mixed epithelial and mesenchymal tumors
Adenosarcoma :
Benign epithelial element
Malignant mesenchymal
element

52. Carcinosarcoma 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.

53. 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

54. Patterns of spread Directly spread (to myometrium, pelvic structures)
pelvic vessels
lymphatics

55. 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

56. Diagnosis Symptoms ( Uterine bleeding ) and signs Ultrasound / MRI
D & C
Pathological diagnosis

57. Staging New staging systems ( FIGO 2009)
Three different staging systems for
1. Leiomyosarcoma
2. ESS and adenosarcoma
3. Carcinosarcoma

58. 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

59. 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

60. Carcinosarcoma
the same as FIGO Staging for endometrial cancer

61. 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

62. 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

63. 3. Hormone therapy ( only used in ESS, low grade) progesterone, letrozol GnRH antagonist

64. 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%.

65. 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.

66. 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.

67. Questions What ‘s the diagnosis ? ( give the evidence)
Which diseases should be excluded?
What is the suitable treatment?
Does this treatment affect fertility?

68. 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.

69. 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.

70. 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.

71. Thank You !