Laboratory Studies
Serum quantitative hCG is used to assess response to therapy and disease status.
A CBC may help detect anemia secondary to bleeding.
Liver enzymes levels may become elevated in the presence of metastasis to the liver.
Imaging Studies
Pelvic ultrasonography
This may show persistent molar tissue in the uterus.
Chest radiography
This test is recommended because the lung is the most frequent site of metastasis.
Computed tomography scanning and magnetic resonance imaging
Chest computed tomography (CT) scanning (optional)
Micrometastases are present in approximately 40-45% of women with nonmetastatic gestational trophoblastic neoplasia (GTN) who have normal chest radiograph findings. [68, 69] The significance of this is not clear. However, having metastasis elsewhere is extremely rare if pulmonary or lower genital tract metastases has not occurred.
If metastases are found on chest CT and not on chest radiograph, they cannot be used for purpose of staging. [4, 5, 30] Only lesions seen on chest radiograph are used to assign the WHO score. However, it has been suggested that a retrocardiac lesion that measures 1 cm or greater on CT can be used for scoring since this may be difficult to detect on a plain chest radiograph. [70]
CT scan of the abdomen and pelvis with contrast and MRI of the head (preferable to CT)
CT and MRI are recommended if the patient has GTN (hydatidiform mole with metastasis to the lungs, choriocarcinoma, or persistent hydatidiform mole).
The lungs, lower genital tract, brain, liver, kidney, and gastrointestinal tract are common sites of metastases.
Procedures
Note the following:
-
Suction and careful sharp curettage could be performed in patients being observed for a hydatidiform mole who have persistent vaginal bleeding and tissue within the endometrial cavity on pelvic ultrasonography.
-
A uterine dilatation and curettage (D&C) performed in a woman with abnormal vaginal bleeding and a positive pregnancy test result may reveal a choriocarcinoma.
-
A D&C may be part of the evaluation of a patient with an elevated serum hCG levels of unknown origin: The tissue is sent for histopathologic examination; examination may reveal a hydatidiform mole (complete or partial) or a choriocarcinoma.
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Rarely is a histopathologic diagnosis of an invasive mole made on a D&C specimen because this requires the identification of destructive invasion of the myometrium by the trophoblasts. Typically, scant or no myometrium is recovered on a D&C specimen.
-
Rarely is the diagnosis of placental site trophoblastic tumor (PSTT) made on a D&C specimen since this usually presents as intermediate trophoblasts infiltrating the myometrium.
-
A complete response (normalization of serum hCG) occurs in 30-40% of patients with newly diagnosed low-risk non-metastatic GTN who undergo a repeat D&C. [71]
-
A hysterectomy is the treatment of choice for PSTT and epithelioid trophoblastic tumor (ETT); the ovaries do not need to be removed if the patient is premenopausal. [29]
Histologic Findings
Complete hydatidiform moles have edematous placental villi, hyperplasia of the trophoblasts, and lack or scarcity of fetal blood vessels.
In the incomplete or partial hydatidiform mole, scalloping of the villi and trophoblastic inclusions occur within the villi. Fetal blood vessels are present.
In a hydropic degeneration of a normal pregnancy, edema of the villi is present, but no trophoblastic hyperplasia. Ghost villi may be observed.
Immunohistochemical staining for p57 may help differentiate between a complete mole and hydropic degeneration. P57 is a paternally imprinted gene that is only expressed in maternal chromosomes. Because all chromosomes of a complete mole are paternal in origin, the nuclei of the villous stroma and the cytotrophoblasts of complete moles do not stain for p57. Hydropic degeneration and partial moles do stain for p57 because they contain maternal chromosomes. [72]
The invasive mole has the same appearance as the hydatidiform mole, but the myometrium is invaded with the presence of hemorrhage and tissue necrosis.
Although the choriocarcinoma has no chorionic villi, it has sheets of trophoblasts, hemorrhage, and necrosis.
In placental site trophoblastic tumor (PSTT), intermediate trophoblasts are found between myometrial fibers, without tissue necrosis. [39]
The epithelioid trophoblastic tumor (ETT) displays nodular nests and cords growth of monomorphic epithelioid cells. [39]
Staging
The official International Federation of Gynecology and Obstetrics staging of gestational trophoblastic neoplasia is as follows [4, 5] :
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Stage I – Confined to the uterus
-
Stage II – Limited to the genital structures
-
Stage III – Lung metastases
-
Stage IV – Other metastases
Each anatomical stage (roman numeral) is followed by the sum of the prognostic scores (see table below) separated by a colon (eg, stage III:5). [73] The FIGO oncology committee at its 2000 meeting recommended that patients could be assigned to a low-risk group if the prognostic score was 0-6 and a high-risk group if the score was 7 or higher.
For patients who relapse, a full restaging to include response to previous chemotherapy can be done. This is different from other gynecologic cancers.
The currently used prognostic scoring index is a modification of the World Health Organization (WHO) classification. It provides points for the presence of a number of prognostic factors.
Table. Prognostic Scoring Index (Open Table in a new window)
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 |
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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.
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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).
Tables
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 |
