SYNOPSIS

GESTATIONAL
TROPHOBLASTIC
DISEASES
Dr. Jeena Raj
Dept. Of Pathology
KAP Viswanatham Medical College
SYNOPSIS

1. Normal Trophoblastic Subpopulations

2. WHO Classification of GTD
3. Hydatidiform mole
4. Benign Trophoblastic Lesions
5. Malignant Trophoblastic Lesions
6. Trophogram in GTD
7. Staging of GTD
8. References
 Primitive Trophoblast

Villous/Extravillous Trophoblast

Cytotrophoblast Syncytiotrophoblast Intermediate Trophoblast

• Small,
• Multinucleated.
mononucleate cell. • Nuclei appear dark and
• Distinct cell border. pyknotic. Villous Chorionic IT
• Small amount of • Numerous microvilli. IT
Implantation IT
eosinophilic • Deeply eosinophilic to
cytoplasm. basophilic cytoplasm.
HYDATIDIFORM MOLES
 HYDATIDIFORM MOLES

 Sporadic :- Complete Hydatidiform mole, Partial Hydatidiform mole

 Inherited forms:- Familial biparental complete hydatidiform moles

COMPLETE HYDATIDIFORM MOLE

 Classic Symptoms/Signs:- Vaginal bleeding accompanied by passing

tissues resembling grape like structures, enlarged uterus, hyperemesis,
hyperthyroidism, preclampsia, Pulmonary embolization, Ovarian theca
lutein cysts.

 Invx:- Elevated Serum Beta- HCG levels, USG- No evidence of fetal

development, Snowstorm appearance
COMPLETE HYDATIDIFORM MOLE
MACROSCOPY

1. Hallmark of “hydatid” or grape like appearance.

2. Voluminous with diffuse hydropic changes
(Hydropic vesicles).
3. No identifiable fetal tissue or normal placental
structures.
 WELL DEVELOPED CHM

•Chorionic villi- Diffuse hydropic changes + Cistern formation.

•Abnormal circumferential trophoblastic hyperplasia.

•Trophoblastic pseudo inclusions.

•Trophoblastic bridging between villi.

VERY EARLY CHM

•Chorionic villi- Small, bulbous, polypoid to phyllodes like configurations

•Abnormal randomly distributed trophoblastic hyperplasia

•Stroma- Cellular myxoid stroma, stellate to plump stromal cells, apoptotic

bodies+.
PROGNOSIS AND RX OF CHM

•15-20% Post molar GTD

•2-3%- Gestational Choriocarcinoma

•Serum B-HCG monitoring.

•P57 (-ve ) Immunohistochemistry.
•Molecular genotyping.
PARTIAL HYDATIDIFORM MOLE

 Clinical Symptoms/ Signs:- Vaginal bleeding is less common, Small or

appropriate uterine size for gestational age.

 Invx:- Serum BHCG normal/ Mildly elevated

 USG- Focal placental cystic changes and a fetus maybe +.

GENETICS OF PHM
MACROSCOPY

Semi transparent hydropic

vesicles involving some but
not all of the chorionic villi.
 MICROSCOPY

• Two populations of chorionic villi:- Enlarged hydropic villi + cistern formation and
surface scalloping and the smaller villi with fibrotic stroma.

• Mild to moderate circumferential trophoblastic hyperplasia.

• Round to oval trophoblastic psuedoinclusions.

• Wandering trophoblast.

• Syncytiotrophoblast “Knuckles”.

• Fetal blood vessels/Nucleated

RBC’s +.
ANCILLARY DIAGNOSTIC STUDY

• P57 + Immunohistochemistry.
• DNA genotyping.
DIFFERENTIAL DIAGNOSIS
 Non Molar Hydropic Abortions
 Digynic Nonmolar Triploid Gestations

 CHM arising in twin gestation or Mosaic gestation

 Trisomy Gestations

 Placental Mesenchymal Dysplasia

Non Molar Hydropic Abortions • Villi with smooth contour.
• No abnormal trophoblastic hyperplasia,
• No trophoblastic atypia, or pseudoinclusions.
• Genotyping- Balanced biallelic genetic profile.

Digynic Nonmolar Triploid • Hydropic villi+.

Gestations • Cistern formation and irregular villous shape.
• Trophoblastic pseudoinclusions and syncytiotrophoblastic
knuckles.
• STR genotyping- To distinguish from partial mole
CHM arising in twin gestation or • Nonmolar villi without trophoblastic hyperplasia + molar villi
Mosaic gestation with trophoblastic hyperplasia and hydropic changes.
• P57/ DNA genotyping.
Trsiomy Gestations • Abnormal villous configurations with
trophoblastic pseudoinclusions and villous hydrops.
• STR genotyping.

Placental Mesenchymal Dysplasia • No significant trophoblastic hyperplasia

and trophoblastic pseudoinclusions.
• The fetus --> IUGR or
signs of Beckwith-Wiedemann syndrome.
PROGNOSIS & RX

 0-5% Persistent GTD.

 0.15% Choriocarcinoma.

 Molar surveillance.
INVASIVE AND METASTATIC HM

 Either a CHM or less often PHM invasion into uterine myometrium

and/ vasculatures.

 Grossly Invasive hydropic villi, Uterine perforations.

 Metastatic mole Molar chorionic villi identified at extrauterine sites,

most common at vaginal wall or pelvis.

 Chemotherapy Highly effective in over 80% of cases.

BENIGN LESIONS
EXAGGERATED PLACENTAL SITE

 Benign, non neoplastic lesion.

 Represents an exaggeration of normal physiological process.

 Increased number of Implantation site Intermediate trophoblastic cells

infiltrating the endomyometrium.

 Overall architecture of implantation site is NOT disturbed.

 DX OF EPS
 Presence of Chorionic villi or fetal parts.
 Lack of confluent/Sheet like growth.

 Absence of macroscopic lesion.

 Preserved endomyometrial architecture.

 Lack of mitosis, Low Ki67 proliferation index(zero).

 More multinucleated trophoblastic cells.

 DDx:- PSTT
PROGNOSIS AND RX
 Involutes following curettage.

 Not associated with persistent GTD.

 No specific treatment or follow up necessary.

PLACENTAL SITE NODULE
 Microscopic lesions with sharply circumscribed borders.

 If Grossly visible- Yellow, tan or hemorrhagic nodule, located in

endometrium or superficial myometrium.

 Microscopy:- Clusters of hyperchromatic and vacuolated chorionic type

intermediate trophoblastic cells in a hyaline matrix.

 DDx: PSTT, ETT, Cervical Squamous Carcinoma.

 Rx- Curettage or hysterectomy.

 No local recurrence or metastasis reported.

NEOPLASTIC LESIONS
CHORIOCARCINOMA
 Highly aggressive malignant tumour Hematogenous dissemination.

 Hydatidiform Mole is the most common preceding gestation. (CHM-

50%).

 Malignant transformation of cytotrophoblastic cells differentiating into

either syncytiotrophoblast or intermediate trophoblast.
 Grossly- Small pin point sized lesions to large circumscribed
hemorrhagic and necrotic masses.

 Microscopy:- Bilaminar/Dimorphic/Biphasic Alternating arrangement

of mononucleate trophoblastic cells and syncytiotrophoblastic cells with
prominent nucleoli, pleomorphic and hyperchromatic nuclei.

 Absence of chorionic villi.

 Blood lakes lined by trophoblastic cells communicate with vascular

channels in normal surrounding tissue.
PROGNOSIS AND RX
 DDx:- Early gestation, Hydatidiform mole, Invasive mole, Gonadal germ
cell tumours, Epithelial malignancies with choriocarcinomatous
differentiation.

 Disseminates hematogenously Lungs> Brain, Liver, GIT, Vagina

 Rx:- Serum BHCG monitoring + Chemotherapy (EMA/CO) 100%

survival.
PLACENTAL SITE TROPHOBLASTIC TUMOUR
 Neoplastic transformation of cytotrophoblastic cells differentiating into
implantation site intermediate trophoblast.
 Macroscopy:- Soft, tan, circumscribed and some poorly demarcated
enlarge and project into uterine cavity or grow into myometrium, with
areas of hemorrhage or necrosis.
MICROSCOPY
 Large polygonal, Implantation site intermediate trophoblastic cells
most often in large nests or masses invading blood vessels.
 Or Multinucleated intermediate trophoblastic cells with vacuolated
cytoplasm and highly atypical nuclei.
 Extensive deposition of eosinophilic fibrinoid material.

 Lumen of blood vessel is preserved.

 No chorionic villi/fetal parts.

PROGNOSIS AND RX
 DDx:- Chroiocarcinoma, ETT, Exaggerated implantation site

 Most are self limited/cured by curettage alone.

 If confined to Uterus Hysterectomy.

 10% to 30%  malignant or extensive disease

Chemotherapy( EMA/CO).
EPITHELOID TROPHOBLASTIC TUMOUR
 Neoplastic transformation of cytotrophoblast differentiating into
chorionic type intermediate trophoblastic cells.
 Altered PI3K signalling pathway.
MACROSCOPY
 Well circumscribed, solid, brown tan, expansile nodule in the
endomyometrium or cervix with cystic areas, hemorrhage and necrosis.
 Microscopy:- Nests and cords of Mononucleate chorionic type
intermediate trophoblastic cells infiltrating the myometrium. Necrosis
and fibrillar eosinophilic material resembling keratin.
 Ability to replace and re epithelialize the endocervical / endometrial
surface epithelium Similarity to keratinizing squamous carcinoma.
PROGNOSIS AND RX
 DDx:-PSTT, Placental site nodule, keratinizing squamous carcinoma of
cervix.

 Majority Behave in benign fashion.

 Some Metastatic diseases Refractory to conventional chemotherapy.

IMMUNOHISTOCHEMISTRY APPROACH
GESTATIONAL TROPHOBLASTIC NEOPLASIA
STAGING SYSTEM
REFERENCES:-