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Gestational trophoblastic disease


Reviewers: Mandolin Ziadie, M.D. (see Reviewers page)
Revised: 7 December 2011, last major update November 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Clinical features

● Carcinoma derived from trophoblastic cells (Am J Surg Pathol 2002;26:914) secondary to a prior pregnancy (normal or abnormal)
● 50% arise from prior moles, 25% from prior abortions, 22% from normal pregnancies (Am J Surg Pathol 1981;5:267) and 3% from ectopic pregnancies or teratomas
● Most aggressive form of gestational trophoblastic disease
● Rapidly invasive and metastasizing; small / necrotic primary tumors may present with metastases
● Most common metastatic sites are lungs, vagina, brain, liver, kidney and bowel; may resemble clear cell carcinoma
● Rarely metastasizes to infant (Arch Pathol Lab Med 1990;114:1079)
Incidence: 1 per 40 moles (usually complete), 1 per 150,000 normal pregnancies in US vs. 1 per 2,500 pregnancies in Nigeria
Risk factors: highest risk for pregnancies of blood type A women and blood type A men (RR: 10.4:1)
● Patients present with bleeding; brown, foul-smelling discharge; high hCG (serum hCG ~ 18,000) that causes changes in other organs, including endocervical glandular hyperplasia, decidual reaction, Arias-Stella reaction, bilateral enlargement of ovaries by theca-lutein cysts (hyperreactio luteinalis) and breast epithelial ductal hyperplasia; abnormal development of uterine spiral arteries (resembles progesterone administration)
● Rarely adjacent to normal villi of normal placenta, associated with placental site trophoblastic tumor or epithelioid trophoblastic tumor
Poor prognosis: age > 39, term pregnancy, long interval to diagnosis, high hCG, blood groups B or AB, large tumor, metastases to brain, GI, liver, > 8 metastases and prior multiagent chemotherapy
● May have better prognosis if intense inflammatory infiltrate at interface between tumor and stroma

Case reports

● 2 month old girl with metastatic disease (Case of Week #200)


● Chemotherapy associated with 100% survival if restricted to uterus vs. 83% survival for all metastatic gestational trophoblastic disease
● Surgery for hemorrhage
● Monitor via serum hCG and chest Xrays

Gross description

● Soft, fleshy, yellow-white, necrotic and hemorrhagic
● May be micro- or macroscopic

Micro description

● Tumor composed of cytotrophoblasts (small, round mononuclear cells with pale cytoplasm) and syncytiotrophoblasts (multinucleated cells) with variable atypia, nuclear pleomorphism, hyperchromasia and prominent nucleoli
● High mitotic activity
● Invades perpendicular to smooth muscle bundles
● May have extensive necrosis with minimal trophoblastic tissue
● Prominent vascular invasion
● Precursor lesion may exhibit increased trophoblastic proliferation
● No villi are present

Micro images

Various images

Positive stains

● All tumor cells - keratin, CEA
● Intermediate trophoblastic cells - HLA-G, hPL and Mel-CAM
● Syncytiotrophoblast - hCG
● Mononucleate cells - Ki-67 (> 90%)

Negative stains


Molecular description

● Establishes androgenetic nature of tumor (if from prior mole)
● Differentiate gestational from germ cell choriocarcinoma

EM description

● Syncytiotrophoblasts: complex cells with multiple nuclei, dense cytoplasm containing dilated endoplasmic reticulum, lysosomes, vesicles and often with numerou microvilli in cell membranes; may have features of epithelial differentiation including tonofilaments and desmosomes
● Cytotrophoblasts: primitive epithelial cells
● Intermediate trophoblasts: transitional features (Hum Pathol 1989;20:370)

Differential diagnosis

● Non-invasive or invasive hydatidiform mole: villi are present
● Placental site trophoblastic tumor: low hCG, composed primarily of intermediate trophoblast
● Germ cell tumors: large adnexal mass, other germ cell tumor elements present, AFP+ and high serum AFP
● Carcinomas with focal choriocarcioma differentiation: usually have areas of typical carcinoma or pleomorphic carcinomas with tumor giant cells (hCG-, hPL-, MelCAM- and normal serum hCG)

End of Placenta > Gestational trophoblastic disease > Choriocarcinoma

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