Gestational trophoblastic diseases (GTD)

1. Gestational trophoblastic diseases (GTD) By MaisaHashem Assistant lecturer of pathology

2. A heterogeneous group of gestational and neoplastic conditions arising from trophoblasts. Include molar gestations and trophoblastic tumors. A common feature of these trophoblastic lesions is the production of HCG

3. The product of conception are divided into three compartments: • 1- Villi and their trophoblasts( villous trophoblasts). • 2- Implantation site (extravillous trophoblasts). • 3- Fetal tissues. • Identification of villi and trophoblasts are needed to confirm diagnosis of abortion. • While presence of placental and fetal tissues needed to exclude extrauterine pregnancy.

5. Trophoblastic cells

6. Trophoblastic cells are the epithelial components of the placenta and are devided into three cytologically and functionally-distinct populations.

7. Cytotrophoblastic cells (CT): They are the germinative cells from which other trophoblastic cells differentiate. They are uniform cells with single nucleus , one or two nucleoli, pale to faintly granular cytoplasm and well defined cell borders.

9. Syncytiotrophoblast(ST) Multinucleated cells with dense amphophilic to basophilic cytoplasm. Dark nuclei,pyknotic, do not contain mitotic figures. The cytoplasm typically contain small vacuoles and large lacunae in which maternal erythrocytes can be identified and a microvillous brush border sometimes lines these lacunae.

11. The intermediate trophoblastic cells (IT): They develop from CT cells on the villous surface. Their predominant location is at the implantation site; which explain why they often called extravillouscytotrophoblasts. Other old name is X cells. They are mononucleated cells, larger than CT cells with pale cytoplasm and large rounded nucleus.

12. WHO classification: • A )Molar lesions • Hydatidiform mole • Complete • Partial • Invasive • metastatic • B) Non molar lesions • Choriocarcinoma • Placental site trophoblastic tumor • Epitheloid trophoblastic tumor • Exaggerated placental site • Placental site nodule • C) Unclassified trophoblastic lesions

13. Hydatidiform mole:

14. Incidence: In Europeans; the disease is infrequent about 1/1000 to 2000 pregnancies. (Partial mole about 1/700) In Asian countries; the incidence of molar pregnancy is much more; however, the exact incidence cannot be determined due to statistical problems.

15. Types: Molar pregnancy can be divided into two subtypes partial and complete mole that differ in their clinicopathological picture and risk to develop persistent GTD.

16. COMPLETE MOLE ( CLASSIC MOLE)

17. Clinical picture: • Uterine enlargement usually greater than expected for gestational age. • Toxaemia of pregnancy usually in the first trimester. • Abortion or abnormal bleeding. • Passage of molar tissues (vesicles). • B. HCG • Markedly elevated • Risk of GTD • 2-3% of patients with complete mole may develop choriocarcinoma. • Risk of persistent GTD is about 20%.

18. Gross picture • Molar pregnancy curetted specimen is one of few specimens that have distinct gross picture • Voluminous bulky specimen. • Oedematous villi. • Translucent vesicles ranging from few mm to 2 cm or more. • Sometimes, oedematous villi and vesicles may not be apparent perhaps due to early gestational age, villi being passed spontaneously before curettage or collapsing villi during suction curettage.

19. Microscopic picture

20. A cistern is completely acellular central cavity within a villous filled with oedema fluid and surrounded by sharply demarcated stromal border. In complete mole. Many but not all villi show cistern formation. All villi are edematous but scattered small villi without cistern are often admixed. Villous edema and cistern formation

22. A vascularity Because fetal development ends very rapidly, villi usually do not have blood vessels.

23. Circumferential trophoblastic proliferation. Degree of trophoblastic proliferation in complete mole is highly variable; usually moderate to marked hyperplasia Occasional cases may show minimal trophoblastic proliferation but still circumfrential.

26. Karyotyping • In complete mole all chromosomes are of paternal origin. • 90% empty ovum fertilized by one sperm (22,x) then it duplicate itself. • 10% empty ovum get fertilized by two sperms. • Despite the paternal origin of complete mole, the mitochondrial DNA is of maternal origin.

27. PARTIAL MOLE

28. Usually presented as missed or spontaneous abortion. ?? the uterus is often normal or small for gestational age. ?? B. HCG is not markedly elevated. Risk of persistent trophoblastic disease is much lower than in complete mole (0,5-5%) and development of choriocarcinoma in partial mole is very rare.

29. Gross picture Like complete mole but it may contain reminants of fetal membranes or a fetus.

30. Microscopic picture:

31. Villi From its name; partial mole imply two types of villi. One is edematous and may show central cistern, other is normal non edematous villi that may be fibrotic. Typically the enlarged villi have irregular scalloped borders with deep enfolding so transverse section of these villi may show trophblastic inclusions in the villous centre. In contrast to complete molar villi that show smooth rounded contour.

33. Trophoblastic proliferation is usually limited but still circumferential. • Another frequent finding of partial mole is microscopic evidence of fetal parts.

35. Karyotyping • It is triploidy. • An apparently normal ovum get fertilized by two sperms. • If associated with fetus, it will show many congenital anomalies and growth restriction.

36. Invasive mole • It is defined as villi of hydatidiform mole (usually complete mole) within myometrium or vascular spaces. • Hysterectomy is required for histological diagnosis.

37. Metastatic mole • It is defined as extrauterine molar villi within blood vessels or tissues (usually lung or vagina)

38. DIFFERENTIAL DIAGNOSIS

39. 1- Complete or partial mole: • Villi, trophoblasts, Fetal tissues, Trophoblastic invagintion. • 2-Molar pregnancy Vs. Hydropicabortus • Hydropicabortus in the fifth week of gestation. Death of embryo causing avascularity of villi and hydropic degeneration. • Hydropic changes affect most villi but minimal or microscopic. • Central cistern is rare but may occur. • If trophoblastic proliferation occur; it is minimal and POLAR NOT CIRCUMFRENTIAL. ??? HCG. • 3- Molar Vs. gestational choriocarcinoma. • As long as chorionic villi are present , no matter how much trophoblastic proliferation is present • Presence of necrosis and destructive infiltrative growth pateren trophoblasts in the myometrium occur in choriocarcinoma.

40. CHORIOCARCINOMA

41. Gestational choriocarcinoma • It is a malignant neoplasm composed of large sheets of biphasic markedly atypical trophoblasts without chorionic villi. • 50% of gestational choriocarcinoma following molar pregnancy. • 25%after abortion. • 22.5% in normal gestation. • 2.5 % associated with ectopic pregnancy.

42. Histopathology • Admixture of syncytiotrophoblasts, cytotrophoblasts and intermediate trophoblasts with marked hge. Necrosis and vascular invasion.

44. Choriocarcinoma does not posses any stroma or blood vessels ,so diagnosis of tumor depending on visualizing viable tumor at periphery of hemorrhage.

46. Immunohistochemistry • All trophoblstic cells are strongly positive for CK. • Syncytiotrophoblasts strong reactive for (b-HCG) but weak for (hpl). Intermediate trophoblasts show the opposite.

47. Differential diagnosis • Previllous trophoblasts from an early gestation. • Persistent molar tissue following molar pregnancy. • Placental site trophoblastic tumor. • Epitheloid trophoblastic tumor. • Undifferentiated carcinoma.

48. Epitheloid trophoblastic tumor

49. Placental site trophoblastic tumor

50. The pathologist determines the histologic diagnosis of the trophoblastic disease, most importantly, if choriocarcinoma is present. In this hydatidiform mole there is atypical trophoblastic proliferation, but villi are still present. The patient is then followed with serial HCG levels