History

Most cases of gestational trophoblastic neoplasia are diagnosed when the serum hCG levels plateau or rise in patients being observed after the diagnosis of hydatidiform mole. If metastases are present, signs and symptoms associated with the metastatic disease, such as hemoptysis, abdominal pain, hematuria, and neurologic symptoms, may be present.

The FIGO 2000 criteria for the diagnosis of GTN after evacuation of a hydatidiform mole include: Serum hCG plateau over 4 weekly measurements (day 1, 7, 14 and 21), more than 10% rise in serum hCG level of three consecutive weekly measurements, elevated serum hCG 6 or more months after evacuation of the mole, or a histologic diagnosis of choriocarcinoma.^[59]

Physical

Note the following:

Metastasis to the lower genital tract present as purple to blue-black papules or nodules. These are extremely vascular and might bleed profusely if biopsied.^[1]
Abdominal tenderness may be present if liver or gastrointestinal metastases have occurred.
Abdominal guarding and rebound tenderness may be present if a hemoperitoneum has occurred due to bleeding from an abdominal metastasis. Bleeding from a metastasis could also result in signs and symptoms of hemorrhagic shock.^{[2, 3]}
Neurologic deficits, from lethargy to coma, can be encountered if brain metastasis has occurred.
Jaundice may be present if liver metastasis causes biliary obstruction.

Causes

Why some hydatidiform moles become malignant and others do not is unknown. However, mounting evidence shows different molecular profiles between nonmalignant and malignant gestational trophoblastic disease.^{[60, 61, 62]}

Differential Diagnoses

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Media Gallery

Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the mesenchyme of the villi.
In this microphotograph of a choriocarcinoma metastatic to the brain, the neuropil is seen on the right and the biphasic (2 cell populations) choriocarcinoma is seen to the left with hemorrhage at the left border of the photograph (H&E stain).

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Table. Prognostic Scoring Index

Table. Prognostic Scoring Index

Prognostic Factor	Points
Age ≥40 y	1
Antecedent pregnancy terminated in abortion	1
Antecedent full-term pregnancy	2
Interval of 4-7 mo between antecedent pregnancy and start of chemotherapy	1
Interval of 7-12 mo between antecedent pregnancy and start of chemotherapy	2
Interval of more than 12 mo between antecedent pregnancy and start of chemotherapy	4
Beta-hCG level in serum is 1,000 to < 10,000 mIU/mL	1
Beta-hCG level in serum is 10,000 to < 100,000 mIU/mL	2
Beta-hCG level in serum is ³100,000 mIU/mL	4
Largest tumor is 3 cm to < 5 cm	1
Largest tumor is 5 cm or greater	2
Site of metastases is spleen or kidney	1
Site of metastases is gastrointestinal tract	2
Site of metastases is brain or liver	4
Number of metastases is 1-4	1
Number of metastases is 5-8	2
Number of metastases is >8	4
Prior chemotherapy with single drug	2
Prior chemotherapy with multiple drugs	4