In the name of GOD

1. In the name of GOD

2. Dr.F Behnamfar MD Gestational trophoblastic Neoplasms (GTN)Danforth

3. GTN is divided into three histologic categories : hydatidiform mole ,  invasive mole (chorioadenoma destruens)  choriocarinoma . Partial hydatidiform moles  Placental site trophoblastic tumors (PSTT)

4. All derived from the human placental trophoblast and the paternal genome • Human chorionic gonadotropin (hCG) is secreted by these neoplasms and serves as a sensitive tumor marker that correlates well with the clinical course for all GTNs exceptPSTT.

5. The initial histologic features of any lesion identified as GTN are less important than the clinical data and hCG level.

6. Complete Hydatidiform Mole Macroscopically : Edema and swelling of virtually Villi without identifiable fetal parts or amniotic membranes Microscopically: The chorionic villi are hydropic with marked interstitial edema . fetal vessels are absent Proliferation of cytotrophoblast and syncytiotrophoblast

7. Complete moles: completely paternal chromosomal composition . most are 46,XX • An empty egg by a haploid sperm followed by reduplication • Empty ovum + 2323 endoreduplication 46xx Homozygous

8. Clinical finding : 1-one third to one half of uterine enlargement 2-Vaginal bleeding 3-Thecalutein cysts 20% 5-pregnancy – induced hypertension (PIH) 4-pulmonary decompensation 6-hyperthyroidism 7-snowstorm (ultrasonography)

9. Partial mole • partial moles often are associated with identifiable fetal parts or amniotic membranes • one haploid maternal and two haploid paternal sets of chromosomes diagnosis : until after evacuation of the pregnancy

10. complete moles : 10% to 30% incidence of malignant • partial mole : fewer than 5% of the patients

11. Invasive mole • with invasion into the myometrium without intervening endometrial stroma • uterine perforation and hemorrhage

12. choriocarcinoma • choriocarcinoma rapidly invades the myometrium and uterine vessels , and systemic metastasis • no chorionic villi are identified • hematogenous embolization • (affinity of trophoblast cell for blood vessel) • Most cases have no tissue for pathologicstudy, hCG level has raise

13. 50% of cases are preceded by hydatidform mole • Gestational choriocarcinoma has been observed several years after last known pregnancy . • Spontaneous regression of the primary uterine site

14. Placental site trophoblastic tumor (PSTT) • Locally invasive neoplasms derived from intermediate cells of the placenta • HPL from cytotrophoblast cell • small amounts of hCG • rare systemic metastasis • significantly more resistant to standard chemotherapy than other forms of GTN • hysterectomy is the initial therapy of choice

15. Risk factors for hydatidiform mole • 1-prevous molar pregnancies • 2-maternal age (advanced maternal age , younger women or adolescents) • Animal fat • Deficiency of folat –caroten and protein • Low socioeconomic state

16. Management GTD • complete physical and pelvic examinations • complete blood count determination • blood chemistry levels , including renal-liver • baseline serum hCG level • chest radiograph • pelvic ultrasonography

17. Evacuation: • suction dilation and curettage • hysterectomy • followed closely after hysterectomy • incidence of malignant squeal: 20% after suction D&C to less than 5% after hysterectomy

18. Follow-up • B-hCG levels every 1 to 2 weeks Until hCG level is undetectable • After the first normal level for 2 to 4 weeks • Every then 1 to 2 months for 6 months • Oral contraceptives

20. Algorithm for diagnosis and treatment of a patient with hydatidiform mole

21. Hysterectomy only if sterillzation desired • After completion of 6 months of hCG normal level pregnancy if desired

22. False – positive hCG Test Results • The heterogeneity of hCG and the variability between different hCG assays may in False – positive test results . • Presence of heterophilic antibodies

23. After evacuation of hydatidiform mole;(9% to 36%) of patients requiring therapy • Pattern of hCG regression • If hCG level plateau or raise for 3 or more consecutive weekly levels • appearance of metastatsis

24. higher frequency of post molar malignant GTN 1- Trophoblastic proliferation 2- Uterine enlargement 3- Theca lute in cysts 4- RDS after molar evacuation 5- post evacuation uterine hemorrhage

25. Persistent GTD • irregular vaginal bleeding • Thecalutein cysts • Uterine subinvolution • Persistently elevated serum hCG level

26. Clinical classification of malignant gestational trophoblastic neoplasia Nonmetastatic GTN A. Not defined in terms of good versus poor prognosis

27. Metastatic GTN Good prognosis (absence of high-risk factors ) • Pretreatment serum B-hCG level < 40,000 IU/ml • Less than 4-month duration of symptoms attributable to disease • No evidence of brain or liver metastasis • No significant prior chemotherapy • No antecedent term pregnancy

28. Poor pregnosis (any single high-risk factor ) • pretreatment serum B-hCG level >40,000 Iu/ml • more than 4-month duration of symptoms attributable to disease • brain or liver metastasis or both • failed prior chemotherapy • antecedent term pregnancy

29. Malignant GTN distant metastases • Gastrointestinal • urologic hemorrhage • Hemoptysis • Neurological symptoms due to cerebral hemorrhage • Clinical hyperthyroidism

30. Four principal pulmunary radiologic patterns snowstorm pattern (Alveolar pattern ) • Discrete rounded densities • Plural effusion • Embolic pattern

31. Management : • Physical and pelvic examinations • Baseline hCG level • Chest radiograph • Pelvic ultrasonography

32. CT of brain , chest , and abdomen –pelvis • Exclude an uterine pregnancy

34. Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia The total score is obtained by adding the individual scores for each prognostic factor . Total score :<4 , low risk ; 5-7 , intermediate risk ;>8 , high risk . Interval :between antecedent pregnancy and start of chemotherapy.

35. WHO Scoring system Score : <4,low risk 5-7mid risk >8 , high risk • Chemotherapy alone is successful in curing 85% of patients with non metastatic and good-prognosis

36. Hysterectomy rarely is indicated as Initial therapy for women with malignant GTN • Persistence of a lung nodule after hCG normalization Should not necessarily surgery • Whole-brain and whole-liver irradiation in conjunction with chemotherapy

37. protocol for treatment of GTD Stage I single agent chemotherapy Resistant combination chemotherapy or hysterectomy with adjuvant chemotherapy Stage II,III low risk single agent chemotherapy high risk combination chemotherapy Resistant second line chemotherapy Stage IV combination chemotherapy radiotherapy Resistant second line chemotherapy

38. liver • 2,000 rd therapy • prevent hepatic hemorrhage • selective occlusion of the hepatic artery

39. Response during therapy • Weekly intervals during therapy • After remission • hCG levels in the normal level • Every 1 month • First year of surveillance .

40. Follow up • Molar pregnancy 6 month GTN 1 year • Metastatic GTN except lung 2 year

41. Recurrence rates after therapy for GTN have been 3% to 26%

42. Late complication • Slight increase in the incidence of spontaneous abortion • Repeat molar 1% • ovarian failure as a result of prolonged multi drug chemotherapy

43. Low incidence of congenital malformations • The incidence of placenta accreta particular , appears to be increased

44. After first pregnancy • We should be a chest radiography . • Serum BhCG after 6-8 weeks of post partum • Placenta should be undergo pathology

45. Towards a safe motherhood