Paper II
Question
What are gestational trophoblastic diseases. Design a labelled diagram to depict the origin of these lesions. Discuss the clinical features, morphology, and complications of these conditions. (2+5+8)
Answer
Definition of gestational trophoblastic disease
- Gestational trophoblastic disease (GTD) refers to a spectrum of tumours and tumour-like conditions arising from abnormal proliferation of pregnancy-associated (gestational) trophoblastic tissue, ranging from benign (hydatidiform mole) to malignant (invasive mole, choriocarcinoma, placental site trophoblastic tumour)
Origin of these lesions (conceptual diagram description) (A labelled diagram cannot be rendered in this text-based answer; the conceptual origin is described below, which would be depicted as a branching diagram from “Fertilization” downward.)
- Normal fertilization (one ovum + one sperm, normal chromosomal complement) → normal pregnancy
- Complete hydatidiform mole: An empty ovum (no maternal chromosomes) is fertilized by one sperm which duplicates its own chromosomes (or by two sperm) → entirely paternal diploid genome (46,XX typically) → no embryonic tissue forms, only diffusely hydropic (swollen) villi
- Partial hydatidiform mole: A normal ovum is fertilized by two sperm (or one sperm that duplicates) → triploid genotype (69,XXY typically) → some embryonic/fetal tissue may be present alongside focally hydropic villi
- Invasive mole: A hydatidiform mole (usually complete) that penetrates/invades the myometrium
- Choriocarcinoma: A malignant neoplasm of trophoblastic cells (cytotrophoblast and syncytiotrophoblast), arising from a preceding molar pregnancy (~50%), normal pregnancy, or spontaneous abortion/ectopic pregnancy — composed purely of malignant trophoblast without chorionic villi
Clinical features
- Hydatidiform mole: Vaginal bleeding in early pregnancy, uterus larger than expected for gestational age, markedly elevated serum beta-hCG, absence of fetal heart sounds, passage of grape-like vesicles per vaginum, early-onset pre-eclampsia, hyperemesis gravidarum (from very high hCG)
- Choriocarcinoma: Irregular vaginal bleeding, markedly elevated beta-hCG, may present with symptoms of metastatic disease (haemoptysis from pulmonary metastases, neurological symptoms from cerebral metastases)
Morphology
- Complete mole: Diffuse hydropic swelling of all chorionic villi, marked circumferential trophoblastic hyperplasia (both cytotrophoblast and syncytiotrophoblast), absence of fetal parts/embryo, “cluster of grapes” gross appearance
- Partial mole: Focal villous hydropic change admixed with normal villi, mild/focal trophoblastic hyperplasia, presence of embryonic/fetal tissue, scalloped villous contours, trophoblastic inclusions
- Choriocarcinoma: Sheets of highly anaplastic cytotrophoblast and syncytiotrophoblast, extensive haemorrhage and necrosis, no chorionic villi formed, marked vascular invasion
Complications
- Uterine perforation/haemorrhage (invasive mole)
- Persistent/malignant gestational trophoblastic neoplasia requiring chemotherapy
- Choriocarcinoma — highly aggressive with early haematogenous metastasis (lungs, brain, liver) but generally excellent response to chemotherapy
- Trophoblastic embolization to lungs (with molar evacuation)
- Recurrence in subsequent pregnancies