Gestational Trophoblastic Disease (GTD) - Trophoblastic Tumours

1. Hydatidiform Mole (Complete and Partial)
2. Invasive Mole
3. Choriocarcinoma
4. Placental Site Trophoblastic Tumour (PSTT)
5. Epithelioid Trophoblastic Tumour (ETT)

1. HYDATIDIFORM MOLE

Etiology / Genetics

Fig. Origin of complete and partial moles - (A) Monospermic complete mole (46,XX), (B) Dispermic complete mole, (C) Partial mole (triploid 69,XXY)

• Incidence: 1 in 1000-2000 pregnancies in the US; twice as common in Southeast Asia
• Risk is higher at extremes of reproductive life (teenagers and women 40-50 years)

Complete Mole - Pathogenesis

• 90%: fertilisation of an "empty" egg (no maternal chromosomes) by a single sperm that undergoes chromosome duplication (monospermic androgenesis) → 46,XX
• 10%: dispermy (two sperm fertilise an empty egg) → 46,XX or 46,XY
• No embryonic development is possible

Partial Mole - Pathogenesis

• An egg with intact maternal chromosomes is fertilised by two sperm → triploid karyotype (69,XXY most commonly)
• Fetal development may occur but with lethal central nervous system and skeletal abnormalities (syndactyly)

GROSS MORPHOLOGY - Hydatidiform Mole

Fig. Complete hydatidiform mole. (A) Gross: markedly distended uterus filled with enlarged, vesicular chorionic villi (grape-like clusters). Adnexa visible on sides. (B) Histology: marked villous enlargement, oedema, cisternae, and circumferential trophoblast proliferation.

• The complete mole appears as a delicate, friable mass of thin-walled, translucent, cystic, grape-like structures - swollen oedematous (hydropic) villi that distend the uterus
• The partial mole shows only focal villous swelling; the rest of the villi appear normal

MICROSCOPY - Hydatidiform Mole

Fig. Partial hydatidiform mole - enlarged oedematous villi with irregular outlines and focal trophoblast proliferation. Normal-sized villi coexist alongside the enlarged ones.

• All or most villi are affected
• Chorionic villi are enlarged, smooth, and oval with central cavitation (cisterns)
• Covered by circumferential biphasic trophoblast proliferation (both cytotrophoblast and syncytiotrophoblast)
• Loose, oedematous stroma; fetal blood vessels typically absent

• Only some villi are enlarged; others are normal
• Trophoblast proliferation is focal and slight
• Irregular villous outlines; "scalloped" contour of villi
• Fetal/embryonic elements may be present

2. INVASIVE MOLE

Gross

• Infiltrative lesion that penetrates and sometimes perforates the uterine wall
• Haemorrhagic areas in the myometrium; hydropic villi visible within the muscle wall

Microscopy

• Hydropic chorionic villi lined by proliferating cytotrophoblast and syncytiotrophoblast invade the myometrium
• Villi may invade parametrial tissue and blood vessels; can embolise to lungs and brain (~5% of complete moles)

Clinical features

• Vaginal bleeding, irregular uterine enlargement, persistently elevated serum hCG after evacuation

3. CHORIOCARCINOMA

GROSS MORPHOLOGY

Fig. Choriocarcinoma. (A) Gross: bulky haemorrhagic mass invading the uterine wall. (B) Microscopy: malignant cytotrophoblast and syncytiotrophoblast with no villi.

• Soft, fleshy, yellow-white tumour with large pale areas of necrosis and extensive haemorrhage
• Invades the myometrium and may extend to the uterine serosa and adjacent structures
• Bulky, destructive, haemorrhagic mass

MICROSCOPY

• Proliferating syncytiotrophoblasts and cytotrophoblasts arranged in sheets and columns
• Chorionic villi are ABSENT - this is the key distinguishing feature
• Abundant mitoses, sometimes abnormal
• Tumour invades the myometrium and penetrates blood vessels
• Extensive areas of necrosis and haemorrhage surrounding viable tumour at the periphery

Metastases

• Hematogenous spread is characteristic
• Lungs (50%), vagina (30-40%), brain, liver, bone, kidney - in descending frequency
• hCG is typically very elevated

Prognosis

• Despite widespread metastases, responds extremely well to chemotherapy (methotrexate ± actinomycin D)
• Near 100% remission rate; most patients can have normal subsequent pregnancies

4. PLACENTAL SITE TROPHOBLASTIC TUMOUR (PSTT)

Gross

• Uterine mass; may follow normal pregnancy (50%), spontaneous abortion, or hydatidiform mole
• Presents with abnormal uterine bleeding or amenorrhea; moderately elevated hCG (much lower than choriocarcinoma)

MICROSCOPY

Fig. PSTT - Markedly atypical trophoblasts splaying apart smooth muscle fibres as they invade the myometrium.

• Composed of polygonal mononuclear or binucleated extravillous trophoblasts with abundant cytoplasm
• Invades without local destruction or haemorrhage (unlike choriocarcinoma)
• Shows tropism for maternal vessels
• No biphasic pattern (no syncytiotrophoblast sheets); no villi

Prognosis

• Localised disease: good prognosis with surgical removal alone
• 10-15% die of disseminated disease

5. EPITHELIOID TROPHOBLASTIC TUMOUR (ETT)

Gross / Clinical

• Most commonly presents following pregnancy with amenorrhea, sometimes a palpable mass
• Most are intrauterine or cervical; extrauterine tumours also occur

MICROSCOPY

Fig. ETT - Sheets of mononuclear trophoblasts with abundant clear cytoplasm and characteristic pink hyaline material (lower right).

• Sheets of mononuclear trophoblast cells with abundant clear cytoplasm
• Characteristic pink hyaline material within the tumour
• Lacks the overt invasive/destructive features of PSTT
• Metastasises most commonly to lungs and bone
• ~10-15% of patients with metastatic disease eventually succumb

Summary Table