Gestational trophoblastic disease

1. PRESENTED BY : MODERATOR:
Dr. Nandakanta Mahanta Dr. M. Naiding
2nd year PGT, Asso Professor
Pathology Dept Dept of pathology
SMCH SMCH
GESTATIONAL TROPHOBLASTIC
DISEASE

2. INTRODUCTION
 Gestational trophoblastic disease
encompasses a spectrum of tumors and tumor-
like conditions characterized by proliferation
of placental tissue, either villous or
trophoblastic.

3. WHO CLASSIFICATION OF GESTATIONAL
TROPHOBLASTIC DISEASE
 NEOPLASMS
 CHOREOCARCINOMA
 PSTT
 EPITHELIOID TROPHOBLASTIC
TUMOR
• NON NEOPLASTIC
LESIONS
 EXAGGERATED PLACENTAL SITE
 PLACENTAL SITE NODULE & PLAQUE
 MOLAR PREGNANCIES
 HYDATIDIFORM MOLE
 COMPLETE
 PARTIAL
 INVASIVE
 ABNORMAL
(NONMOLAR) VILLOUS
LESIONS

4. PLACENTA
The normal term placenta measures
 15–20 cm in diameter
 1.5-3 cm in thickness
 450–600 g
main components : umbilical cord, membranes (amnion and
chorion), villous parenchyma, maternal decidual tissue
.

5. fetal surface (chorionic
plate Maternal surface

6. EMBRYOLOGY

7. The ovum is fertilized in the FT &
develops rapidly
reaches the endometrial cavity as a
blastocyst.
outer cell layer of the blastocyst-
differentiated into trophoblast
attaches to & penetrates the
endometrium on the 6th to 7th
postovulatory day

8.  offshoots from the surface
of trophoblast- VILLI
 Trophoblast + EEM =>
chorion
 the villi arising =>
chorionic villi.

9.  trophoblast - single layer cells.
 two distinct layers- formed.
 syncytiotrophoblast or
plasmodiotrophoblast
 cytotrophoblast ( Langhan’s
layer)
Normal placenta. First-trimester chorionic villi

10. Third-trimester chorionic villi
stroma with
dense network of
dilated
capillaries
surrounded by
markedly
thinned-out ST
and CT.

11. MORPHOLOGY OF TROPHOBLAST
 dimorphic pattern composed of
mononucleate trophoblastic
cells and primitive
syncytiotrophoblastic cells
 that resemble choriocarcinoma.
PREVILLOUS TROPHOBLAST

12. CYTOTROPHOBLAST
 A layer of uniform cells -
polygonal to oval in shape
• single, round–oval nuclei,
• Clear cytoplasm,
• Distinct cell borders
• mitotic activity is evident.

13. SYNCYTIOTROPHOBLAST
 overlies the CT
 composed of - large, multinucleate cellular mass ,Dense
amphophilic cytoplasm, nuclei are dark and pyknotic.
• They do not show mitotic activity.

14. INTERMEDIATE TROPHOBLAST
 constituent of villous Trophoblast
 most prevalent in extravillous sites.
 IT developing from the trophoblastic shell invades the endometrium and
myometrium at the implantation site.
 Subpopulations of IT are-
 (villous IT),
 (implantation site IT)
 (chorionic IT).

15. IMMUNOHISTOCHEMICAL FEATURES OF
TROPHOBLAST
• β-subunit of hCG,
• hPL
• PLAP
• inhibin
• Lmw CK

16. HYDATIDIFORM MOLE
 Abnormal placentation with Hydropic
swelling of the chorionic villi &
trophoblastic proliferation.
 at any age, [teenagers & 40 and 50 years]
 Two types—complete and partial

17. R/F OF MOLAR PREGNANCY
increasing reducing
 diets deficient in vitamin
A precursors
 a history of a previous
mole
 increased consumption
of carotene
 history of previous term
birth

18. COMPLETE HYDATIDIFORM MOLE
A, most commonly
(90%):
arise from
fertilization of an
empty ovum by a
single
sperm that
undergoes
duplication of its
chromosomes.
(androgenesis)
B, Less commonly,
(10%)
complete moles
arise from dispermy
in which two sperm
fertilize an empty
ovum.

19.  hydropic swelling of the majority of villi,
 a variable degree of trophoblastic proliferation and atypia.
 Fetal tissue usually not present.
 2.5% risk of subsequent choriocarcinoma
 15% risk of persistent or invasive mole.

20. C/F
 uterus disproportionately large for the stage of pregnancy.
 Serum hCG levels continue to rise after the 14th week
 Evidence of toxemia of pregnancy (hypertension, edema,
albuminuria) during the early stages of the pregnancy
 vaginal bleeding

21. Complete hydatidiform mole

22. MICROSCOPIC
 involve all or most -villous tissue
 Two key features: trophoblastic proliferation
& villous edema.
 The chorionic villi are enlarged, scalloped in
shape
 central cistern formation - prominent central
space that is entirely acellular
 The villous stroma has a distinctive pale blue-
grey appearance

23. IMMUNOHISTOCHMICAL
 hCG
 PLAP
 P57kip2 protein.
 well expressed in the CT and villous mesenchyme of normal
pregnancy, spontaneous abortions, and partial moles,
 absent or markedly decreased in complete moles

24. THERAPY
 evacuation by curettage.
 f/b sequential quantitative determination of the ß-hCG

25. PARTIAL MOLE
 A hydatidiform mole having two populations of chorionic
villi, one of normal size and the other hydropic, with focal
trophoblastic proliferation

26.  fertilization of an egg with two
sperm
 karyotype : triploid (e.g., 69,XXY
Or 69XXX) or occasionally
tetraploid (92,XXXY).
 extra material is of paternal
derivation ( ‘diandric triploidy’)
 Fetal tissues +ve .
 increased risk of persistent molar
disease,
 not associated with
choriocarcinoma.

27. CLINICAL FEATURES
 Vaginal bleeding
 Uterus size- small for date
 At risk for preeclampsia
 S- beta hCG are in the low or normal range for
gestational age

28. GROSS
 less than 100 or 200 Ml
 villi may be grossly evident and
recognizable as molar, but are
smaller than those found in a
complete mole.

29. MICROSCOPIC FINDINGS
• two populations : small, fibrotic “normal”
villi & hydropic villi
• enlarged villi with central cavitation
 geographic, scalloped border, with irregular
trophoblastic invaginations and inclusions
• minimal trophoblast hyperplasia

30.  the presence of fetal
erythrocytes within placental
vessels - an evidence of
functioning villous circulation.

31. INVASIVE MOLE (chorioadenoma
destruens)
 hydropic villi invade the myometrium or blood vessels or,
deported to extrauterine sites.
 not a true neoplastic disease, but often clinically considered to
be malignant - can invade the myometrium and metastasize.

32.  may embolize to distant sites, lungs and brain, but do not grow in these
organs as true metastases, even without chemotherapy they eventually
regress.
 vaginal bleeding and irregular uterine enlargement.
 persistently elevated serum HCG
 responds well to chemotherapy but may result in uterine rupture and
necessitate hysterectomy.

33. GROSS FINDING
 In the uterus, erosive,
hemorrhagic lesion extending
from the uterine cavity into the
myometrium.
 Molar vesicles often are grossly
apparent.

34. MICROSCOPIC FINDING
 presence of molar villi along with
trophoblast
 Trophoblastic proliferation with atypia
 Hydropic swelling is not that marked, 4–
5 mm in diameter
 In metastatic sites, the diagnosis is based
on the presence of villi.
 Lesions at distant sites : molar villi
confined within blood vessels without
invasion into adjacent tissue

35. ABNORMAL (NONMOLAR) VILLOUS
LESIONS

36.  Various non molar, villous lesion with histological features
simulating partial HM
 HISTOPATHOLOGY:
 Chorionic villi display some degree of irregularity in size & shape,
with focal , mild, trophoblastic hyperplasia (sometimes menifested
as syncytiotrophoblastic “snouts”) & occasional trophoblastic
inclusion.

37. NON NEOPLASTIC LESIONS

38. PLACENTAL SITE NODULE
 small, well-circumscribed nodular aggregates of chorionic-
type intermediate trophoblastic cells that are embedded in a
hyalinized stroma.
 benign counterpart of the epithelioid trophoblastic tumor.

39. MICROSCOPIC FEATURES
 small nodular / plaque-like
lesions with rounded, well
circumscribed borders
 thin rim of chronic inflammatory
cells
 central hyalinized extracellular
matrix

40. EXAGGERATED PLACENTAL SITE
REACTION
 exuberant infiltration of the myometrium by implantation site
intermediate trophoblast

41. MICROSCOPIC
 extensive infiltration of the
endometrium and myometrium
by implantation site
intermediate trophoblastic
cells, multinucleated.

42. TROPHOBLASTIC TUMORS
(NEOPLASTIC DISEASES)

43. CHORIOCARCINOMA
 highly malignant epithelial tumor arising from the
trophoblast of any type of gestational event, most often a
hydatidiform mole
 a biphasic proliferation of mononucleate trophoblast and
syncytiotrophoblast
 Chorionic villi are not a component, Exception : intra
placental choreocarcinoma

44. CLINICAL FEATURES
 Abnormal uterine bleeding.
 lesions restricted to the myometrium remain asymptomatic
 lungs are the most frequent sites for metastasis.
 Thyrotoxicosis and hemorrhagic events in the central nervous
system, liver, and gastrointestinal or urinary tracts

45. GROSS FINDINGS
dark red, hemorrhagic mass with
a shaggy, irregular surface and
variable amounts of necrosis
well circumscribed and
hemorrhagic Liver mets

46.  biphasic pattern of CT &
multinucleated ST
 prominent hemorrhage, necrosis,
and vascular invasion
 Does not provoke a stromal
response or host
neovascularization.

47.  pseudovascular network and blood-lakes that are lined by trophoblastic
cells
 ‘‘vasculogenic Mimicry” : generation of microvascular-like channels by
neoplastic cells
 devoid of adequate stromal support -> hemorrhage

48. CLINICAL BEHAVIOUR & TREATMENT
 Metastasis is characteristic : lungs (50%) and vagina
(30% to 40%), followed by, brain, liver, bone and kidney
 beta-hCG monitoring and chemotherapy

49. PLACENTAL SITE TROPHOBLASTIC
TUMOR
 composed of neoplastic implantation site intermediate trophoblastic
cells.
 less than 3% of GTD cases

50. GROSS
 well circumscribed
 only focal areas of hemorrhage or necrosis, may present.
 Invasion frequently extends to the uterine serosa

51. scattered
atypical and multinucleated cells.
Neoplastic
extravillous CT cells are infiltrating
the myometrium

52.  vascular invasion in which blood
vessel walls are extensively
replaced by trophoblastic cells
and fibrinoid material
 “transformed’’ blood vessels
are are diagnostic for PSTT

53. EPITHELIAL TROPHOBLASTIC TUMOR
 neoplastic transformation of cytotrophoblastic cells that differentiate
toward chorionic-type intermediate trophoblastic cells.

54. GROSS FINDING
 solitary,discrete nodules that
deeply invaded the cervix or
myometrium
 solid or cystic

55. MICROSCOPIC FINDINGS
abundant hyalinized
stroma
infiltrated by scattered,
degenerate-appearing
intermediate
trophoblastic cells

56. DIFFERENTIAL DIAGNOSIS