Gestational trophoblastic neoplasia differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]

Overview

Choriocarcinoma must be differentiated from non neoplastic diseases, neoplastic diseases, and other causes of bleeding during pregnancy.

Differentiating choriocarcinoma from other diseases

Choriocarcinoma must be differentiated from other non-neoplastic diseases such as:

• Hydatidiform mole

Choriocarcinoma must be differentiated from other neoplastic diseases such as:

• Invasive hydatidiform mole
• Placental site trophoblastic tumor (PSTT)
• Mixed germ cell tumor - esp. for testicular and ovarian tumors

Choriocarcinoma must be differentiated from other causes of bleeding during pregnancy:

• Spontaneous abortion
• Ectopic pregnancy
• Normal term pregnancy

Differential Diagnosis	Clinical Features						Karyotype	Immunostaining							Management
	Presenting Complaints	Potential for Neoplastic Conversion	Beta Human Chorionic Gonadotropin (Beta-hCG) Baseline Levels	History of Pregnancy	Theca Leutin Cysts	Metastatic Route		Cytokeratin 18	HLA-G	Human Chorionic Gonadotropin (hCG)	Transformation-Related Protein 63 (P63)	Human Placental Lactogen (hPL)	Melanoma Cell Adhesion Molecule (Mel-CAM)	Ki67
Complete Hydatidiform Mole	Vaginal bleeding Inappropriately large for date uterine size Hyperemesis Vaginal passage of grape-like vescicles	High rate of progression (15-20%)	Extremely high levels ( > 100000 mIU/ml in half of the patients	Not related	Present	Benign	46, XX or 46 XY (Paternal dispermy)	Absent	Absent	Extremely elevated	Absent	Absent	Absent	Absent	Dilation and curettage (suction)
Partial Hydatidiform Mole	Vaginal bleeding	< 5 % progression rate	Highly elevated ( > 100000 mIU/ml in one in ten patients)	Not related	Absent	Benign	69,XXY or XYY	Absent	Absent	Highly elevated	Absent	Absent	Absent	Absent	Dilation and curettage (suction)
Invasive Molar Pregnancy	Vaginal bleeding Elevated beta-hCG	Neoplastic	High	Consequence of molar pregnancy	May be present	Hematogenous	69,XXY or XYY	Positive	Positive	Highly elevated	Absent	Absent	Absent	Absent	Chemotherapy (Methotrexate)
Choriocarcinoma	Vaginal bleeding Weight loss	Neoplastic	High	Approximately half of the cases occur as a consequence of molar pregnancy Quarter of the cases follow abortion or tubal pregnancy Rest follow term or pre-term pregnancy	Present	Hematogenous
Placental-site Trophoblastic tumor (PSTT) and Epitheloid Trophoblastic Tumor (ETT)	Vaginal bleeding	Neoplastic	Moderatley elevated (< 1000 mIU/ml in majority of patients)	About 60% follow term pregnancy 40 % follow molar pregnancy or abortion	Absent	Lymphatic	46,XX or XY	Positive	Positive		Negative (Positive in ETT)	Positive (Negative in ETT)	Positive (Negative in ETT)	Positive ( >1% in PSTT and >10% in ETT)	Hysterectomy
Ovarian Tumors	Vagina bleeding or discharge Weight loss Urinary frequency/urgency Change in bowel habits Loss of appetite Pelvic pressure/pain Abdominal pain	Neoplastic	Elevated (Dysgerminoma and Embryonal carcinoma)	Overall incidence in pregnancy is 2.4-5.7% (1/300 to 1/556 pregnancies) Incidence of malignancy is 1/15,000 to 1/32,000 pregnancies Germ cell and epithelial tumors are most common	Absent	Direct extension or seeding	46,XX	Absent (Epithelial tumors may be positive for cytokeratin AE1/AE3)	Positive	Elevated in dysgerminomas and embryonal carcinoma)	Positive (especially in epithelial cancers)	Positive	Positive	Positive	Surgical debulking Intravenous/intraperitoneal chemotherapy
Spontaneous Abortion	Vaginal bleeding Lower abdominal pain Lower back pain Vaginal passage of fetal tissue Reduced uterine size and regression of signs and symtoms of pregnancy Firm cervix	Not applicable	Decline in levels within 24 hours	Aneuploid pregnancy History of recurrent pregnancy loss	Absent	Not applicable	47,XX, +21 or 47, XY, +21 (Down's syndrome) 47,XX,+18 or 47, XY, +18 (Edward's syndrome) 47,XX, +13 or 47, XY, +13 (Patau syndrome)	Absent	Absent	Progressive decline	Negative	Negative	Negative	Negative
Ectopic Pregnancy	Abdominal/pelvic pain Vaginal bleeding Amenorrhea Nausea Syncope	Not applicable	Failure of hCG doubling (especially during the first 8 weeks)	Previous ectopic pregnancy Intrauterine exposure to diethylstillbestrol Current use of intrauterine contraceptive device Advanced maternal age	Absent	Not applicable	46,XX or 46, XY	Negative	Negative	A rising β-hCG concentration that fails to reach 50% or plateaus	Negative	Negative	Negative	Negative	Expectant management (Failure of transvaginal ultrasonography to show the location of the gestational sac and the serum levels of β-hCG and progesterone are low and declining) Surgical laproscopy
Normal Term Pregnancy

Clinical Features	Complete Hydatidiform Mole	Partial Hydatidiform Mole	Invasive Molar Pregnancy	Choriocarcinoma	Placental-site trophoblastic tumor (PSTT) and Epithelioid trophoblastic tumor (ETT)
Presenting Complaints				Vaginal bleeding
Neoplastic Conversion				Neoplastic	Neoplastic
Beta Human Chorionic Gonadotropin (Beta-hCG) baseline levels			High	High
History of Pregnancies			Consequence of molar pregnancy
Metastatic Route	Benign	Benign	Hematogenous	Hematogenous	Lymphatic
Management	Dilation and curettage (suction)	Dilation and curettage (suction)		Chemotherapy (Methotrexate)	Hysterectomy