Gestational Trophoblastic Neoplasia (GTN)

Prof. Gamze Mocan Kuzey M.D.Near East UniversityFaculty of MedicineDepartment of Pathology

Gestational Trophoblastic Neoplasia (GTN) Proliferation of pregnancy-associated

trophoblastic tissue of progressive malignant potential

Benign hydatiform mole Invasive mole (chorioadenoma

destruens) Placental site trophoblastic tumor

(PSTT) Choriocarcinoma

GTN Pathogenesis geographic distribution, dietary,

genetic components An accentuation of the hydropic

swelling encountered in a blighted ovum (Hertig&Mansell)

Cytogenetic studies of moles 90% have 46XX diploid patterns

GTN Androgenesis : chromosome banding

patterns of cells from molar tissues and parents strongly suggest that the entire chromosome complement of the mole comes from the SPERM 80% of moles → BENIGN 20% of moles → further complications

( + invasive mole) 2-3% of moles → choriocarcinoma

Importance of GTN Benign mole – common complication of

gestation, one in every 2000 pregnancies

Monitoring the circulating levels of HCG Determination of the early development of

the more malignant forms Once a dreaded and fatal complication

Choriocarcinoma – highly responsive to chemotherapy

Mole Hydatiform Hydropic swelling of chorionic villi Absence or inadequate development

of vascularization of villi Variable degrees of hyperplasia and

anaplasia of the chorionic epithelium Thin layer of chorionic epithelium

Cytotrophoblast Syncytial trophoblast

Incomplete mole(Partial Mole) Diffuse & massive villous edema (in some villi) No trophoblastic proliferation Focal slight trophoblastic proliferation Fetus is present or amnion is present Triploid karyotype Rarely followed by choriocarcinoma Absence of atypia HCG staining in tissue is weak

in specimens from Spontaneous abortions

Invasive Mole (Chorioadenoma Destruens) Biologically benign cellular invasive

mole Penetrates Perforates

Invasion of the myometrium by well-developed embryonic villi

Proliferation of both cuboidal and syncytial chorionic epithelial components

Uterine wall

Invasive Mole

Locally destructive tumor Invasion of parametrial tissues Embolization → lungs, brain Regression vaginal bleeding, irregular uterine

enlargement Rupture of the uterus → Hemorrhage Sepsis

Death

Placental Site Trophoblastic Tumor (PSST) Β-hCG Excellent prognosis

Stage I or II (localized disease) Less than 2 year interval from the prior

pregnancy to diagnosis Poor prognosis

Tumor diagnosed 4 or years following pregnancy

Lung involvement Advanced stage 10% disseminated metastasis & death

Placental Site Trophoblastic Tumor Syncytial cytotrophoblasts - on the

chorionic villi Intermediate trophoblast – in the

implantation site & placental membranes

MONONUCLEAR CELLS with abundant cytoplasm

Syncytiotrophoblasts produce hCG Intermediate trophoblast cells – weakly

immunoreactive human placental lactogen (HPL)

Placental Site Trophoblastic Tumor

Less than 2% GTT Endometrial infiltration + PSST’s may be preceded by:

Normal pregnancy (1/2 of the cases) Spontaneous abortion (1/6 of the

cases) Hydatidiform mole (1/5 of the cases)

Placental Site Trophoblastic Tumor

Intermediate trophoblasts compose the placental site trophoblasts & residual plasental site (implantation site nodule) following pregnancy → may give rise to PSTT’s

Differential diagnosis

Normal exaggerated placental implantation site trophoblasts

Mel-Cam Ki-67

Biomarkers that detect trophoblastic cell proliferation

Synctialendometritis

Choriocarcinoma Uncommon condition

1/20,000 – 30,000 pregnancies in USA 1/2500 pregnancies in Asian & African

countries 50% arise in hydatiform moles 25% arise in previous abortions 22% arise in normal pregnancies The rest in ectopic pregnancies, genital

and extragenital teratomas Occurence in males

Choriocarcinoma Epithelial malignancy of trophoblastic

cells Derived from any form of previous

normal or abnormal pregnancy Most cases arise in the uterus Ectopic pregnancies – extrauterine sites

of origin One of the most rapidly invasive widely

metastasizing malignancies

Choriocarcinoma 1/40 hydatiform moles →

choriocarcinoma 1/150,000 normal pregnancies →

choriocarcinoma

Morphology Epithelial, cellular Chorionic villi (-) Abnormal proliferation of cytotrophoblast & syncytial trophoblast

Anaplasia Abnormal mitoses (+) Invasion of the myometrium Penetration of blood vessels & lymphatics Extension out (uterine serosa, adjacent structures) Hemorrhage Ischemic necrosis, cystic softening Secondary inflammatory infiltration

Metastases: lungs, bone marrow, liver, vagina, brain, kidney

HCG titers to levels above those encountered in moles. SUCH EXTREME ELEVATIONS → DIAGNOSIS OF CHORIOCARCINOMA