eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Oncology

Gestational Trophoblastic Neoplasia: Differential Diagnoses & Workup

Author: Enrique Hernandez, MD, FACOG, FACS, Chairman, Department of Obstetrics and Gynecology, Director of Gynecologic Oncology, Abraham Roth Professor of Obstetrics, Gynecology and Reproductive Science, Professor of Pathology, Temple University Hospital, Temple University School of Medicine
Contributor Information and Disclosures

Updated: Sep 24, 2008

Differential Diagnoses

Biliary Obstruction
Ovarian choriocarcinoma
Bladder Cancer
Pregnancy Diagnosis
Brain tumors
Quiescent GTN
Cerebrovascular accidents
Urothelial Tumors of the Renal Pelvis and Ureters
hCG-secreting germ cell tumors
Hemorrhagic Cystitis: Noninfectious
Nephrolithiasis

Other Problems to Be Considered

  • The differential diagnosis will depend on whether or not metastasis has occurred and to what organs.
  • In the absence of an identifiable preceding pregnancy, the possibility of an hCG-secreting germ cell tumor needs to be entertained. In the presence of stable low levels of serum hCG, the differential diagnosis includes a false positive or "phantom" hCG, pituitary hCG, or quiescent gestational trophoblastic disease.30,31,32
  • A normal intrauterine pregnancy needs to be excluded if the serum hCG levels start to rise in a patient being observed after evacuation of a hydatidiform mole.

Workup

Laboratory Studies

  • Serum hCG is used to assess response to therapy and disease status. 
  • A CBC may help detect anemia secondary to bleeding.
  • Liver enzymes 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 radiograph: This test is recommended because the lung is the most frequent site of metastasis.
  • CT scan of the chest (optional): Micrometastases are present in approximately 40-45% of women with nonmetastatic gestational trophoblastic neoplasia (GTN) who have normal chest radiograph findings.33,34 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.1,2,35
  • 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 frequent sites of metastases.

Procedures

  • Suction and 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.
  • 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.
  • In a patient with GTN, a hysterectomy will reduce the total number of chemotherapy cycles required to achieve a remission.36,37
  • A hysterectomy is the treatment of choice for PSTT; the ovaries do not need to be removed if the patient is premenopausal.14

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.

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.

Staging

The official International Federation of Gynecology and Obstetrics staging of gestational trophoblastic neoplasia is as follows:1,35

  • Stage I – Confined to the uterus
  • Stage II – Limited to the genital structures
  • Stage III – Lung metastases
  • Stage IV – Other metastases

Each stage is subclassified further according to a prognostic scoring index. If the risk factors are unknown, no substage is assigned. If the prognostic score is 6 or less, the substage is A (eg, IIIA is equal to lung metastasis with a prognostic score of 6 or less). If the prognostic score is 7 or greater, the substage is B.38

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, as follows:

  • Age 40 years or older = 1 point
  • Antecedent pregnancy terminated in abortion = 1 point
  • Antecedent full-term pregnancy = 2 points
  • Interval of 4 months to less than 7 months between antecedent pregnancy and start of chemotherapy = 1 point
  • Interval of 7-12 months between antecedent pregnancy and start of chemotherapy = 2 points
  • Interval of more than 12 months between antecedent pregnancy and start of chemotherapy = 4 points
  • Beta-hCG level in serum is 1000 mIU/mL but less than 10,000 mIU/mL = 1 point
  • Beta-hCG level in serum is 10,000 mIU/mL but less than 100,000 mIU/mL = 2 points
  • Beta-hCG level in serum is 100,000 mIU/mL or greater = 4 points
  • Largest tumor is 3 cm but less than 5 cm = 1 point
  • Largest tumor is 5 cm or greater = 2 points
  • Site of metastases is spleen or kidney = 1 point
  • Site of metastases is gastrointestinal tract = 2 points
  • Site of metastases is brain or liver = 4 points
  • Number of metastases is 1-4 = 1 point
  • Number of metastases is 5-8 = 2 points
  • Number of metastases is more than 8 = 4 points
  • Prior chemotherapy with single drug = 2 points
  • Prior chemotherapy with multiple drugs = 4 points

More on Gestational Trophoblastic Neoplasia

Overview: Gestational Trophoblastic Neoplasia
Differential Diagnoses & Workup: Gestational Trophoblastic Neoplasia
Treatment & Medication: Gestational Trophoblastic Neoplasia
Follow-up: Gestational Trophoblastic Neoplasia
Multimedia: Gestational Trophoblastic Neoplasia
References
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References

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Further Reading

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Keywords

gestational trophoblastic disease, gestational trophoblastic tumors, GTD, GTN, hydatidiform mole, invasive mole, chorioadenoma destruens, choriocarcinoma, placental site trophoblastic tumor, PSTT, gestational trophoblastic neoplasia, molar pregnancy, uterine cancer, uterine tumor, cancer of the uterus

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Contributor Information and Disclosures

Author

Enrique Hernandez, MD, FACOG, FACS, Chairman, Department of Obstetrics and Gynecology, Director of Gynecologic Oncology, Abraham Roth Professor of Obstetrics, Gynecology and Reproductive Science, Professor of Pathology, Temple University Hospital, Temple University School of Medicine
Enrique Hernandez, MD, FACOG, FACS is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American College of Surgeons, American Medical Association, American Society for Colposcopy and Cervical Pathology, Association of Professors of Gynecology and Obstetrics, Johns Hopkins Medical and Surgical Association, Pennsylvania Medical Society, Philadelphia County Medical Society, and Society of Gynecologist Oncologists
Disclosure: Nothing to disclose.

Medical Editor

Robert C Shepard, MD, FACP, Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International
Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals Obstetrics/Gynecology Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board; Vice Chair for Research and Education, Department of Obstetrics/Gynecology, Tufts Medical Center
David Chelmow, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Phi Beta Kappa, Sigma Xi, Society for Gynecologic Investigation, and Society for Medical Decision Making
Disclosure: Nothing to disclose.

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