Uterine myoma and sarcoma Fudan University Weiwei Feng, MD,Ph.D Email:jingsakura@gmail

1. Uterine myomaand sarcomaFudan UniversityWeiwei Feng, MD,Ph.DEmail:jingsakura@gmail.com

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

4. 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. 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 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

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

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 Submucous myoma Cervical cancer Endometrial cancer

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

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 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