Gestational trophoblastic disease

Topic Completed: 1 February 2017

Minor changes: 20 January 2021

Copyright: 2002-2021,, Inc.

PubMed search: Gestational choriocarcinoma placenta [title]

Sonali Lanjewar, M.B.B.S.
Raavi Gupta, M.D.
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Cite this page: Lanjewar S, Gupta R. Choriocarcinoma. website. Accessed March 4th, 2021.
Essential features
  • Malignant trophoblastic tumor comprising a trimorphic proliferation of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast with absence of chorionic villi
  • Most aggressive form of gestational trophoblastic disease
  • It is rapidly invasive with early hematogenous metastasis, however over 90% of patients are cured by treatment
  • 50% are diagnosed following a term pregnancy, 25% after a hydatidiform mole (Obstet Gynecol 2006;108:176)
  • Complete mole may progress to choriocarcinoma in 2 - 3% and partial mole in < 0.5% of cases
  • Most common symptom is vaginal bleeding (Lancet 2000;356:36)
  • Primary nongestational choriocarcinoma, though rare, has been reported in ovary, lung, liver, mediastinum and adrenal gland; also CNS, esophagus, fallopian tube, stomach, testis
  • Europe and North America: 1 per 40,000 pregnancies and 1 per 40 hydatidiform moles
  • Southeast Asia and Japan: rates are higher at 9.2 and 3.3 per 40,000 pregnancies, respectively (Am J Obstet Gynecol 2010;203:531)
Risk factors
  • Prior hydatidiform mole, ethnicity, advanced maternal age, long term oral contraceptive use and specific blood group
  • Complete mole carries 1,000 times more risk of developing choriocarcinoma than any other pregnancy event
  • Women of Asian, American Indian and African American descent are at increased risk (Am J Obstet Gynecol 2010;203:531)
  • Highest risk in women of blood group A married to men of the same blood group
Clinical features
  • Women of reproductive age; rarely young girls and postmenopausal women
  • Most common symptom is vaginal bleeding
  • Untreated choriocarcinoma characteristically presents with early hematogenous metastases
  • Common metastatic sites include lung, brain, liver, kidney and bowel
  • Metastasis may be clinically solitary and may occur in unusual locations and often present with massive hemorrhage
  • Fetus is rarely involved, even in cases of widespread metastatic disease
  • Primary uterine tumor may be inconspicuous or altogether absent in patients with disseminated choriocarcinoma
  • Patients can also have symptoms due to hypersecretion of hCG, which include hyperplasia of endocervical glands, decidual reaction (both endometrial and ectopic), Arias-¬≠Stella phenomenon, bilateral enlargement of the ovaries by theca lutein cysts ("hyperreactio luteinalis") and hyperplasia of mammary lobules
  • Detection of ovarian theca ¬≠lutein cysts long after a case of choriocarcinoma has been treated may indicate persistence of disease
  • Serum and urine hCG: patients with stages I, II and III disease are followed with weekly hCG test until undetectable, for 3 consecutive weeks and then monthly for 12 months
  • Patients with stage IV disease are followed similarly but for 24 months
  • CT, MRI: to determine the extent of uterine involvement and to detect presence of metastasis
Prognostic factors
  • Prognostic score is calculated based on following variables: age ≥ 40, antecedent pregnancy, interval months from index gestation, pretreatment hCG levels, largest tumor size, site and number of metastases and previous failed chemotherapy (FIGO / WHO scoring system, Int J Gynaecol Obstet 2003;83:175, PDF)
Case reports
Gross description
  • Bulky, destructive, single to multiple dark masses in uterus with extensive central hemorrhage and variable amount of necrosis
  • Tumor may arise in extrauterine sites such as the fallopian tube and ovary which are common sites of ectopic pregnancy
Microscopic (histologic) description
  • Tumor may be diffusely infiltrative or may have cohesive sheets of trimorphic malignant trophoblasts consisting of intermediate trophoblast and cytotrophoblast rimmed with syncytiotrophoblast
  • Presence of marked central hemorrhage and necrosis
  • Striking cytologic atypia and numerous mitotic figures
  • Lymphovascular invasion is common
  • Characteristically, there is absence of chorionic villi; presence of villi excludes choriocarcinoma
Microscopic (histologic) images

Contributed by Sonali Lanjewar, M.D.


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Metastatic choriocarcinoma

Cytology description
  • Rare reports of choriocarcinoma diagnosed on Pap smear (Diagn Cytopathol 2016;44:324)
  • Two cell populations: large atypical cells with abundant cytoplasm and intracellular globules and small atypical cells with hyperchromatic nuclei, high N/C ratios
  • Tumor cells are positive for hCG
Positive stains
Negative stains
Electron microscopy description
  • Syncytiotrophoblasts: complex cells with multiple nuclei, dense cytoplasm containing dilated endoplasmic reticulum, lysosomes, vesicles and often with numerous 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)
Molecular / cytogenetics description
  • Highly complex karyotypes with recurrent 7p amplification and 8p deletion
  • XX sex chromosome composition is present in a majority of choriocarcinoma
  • DNA polymorphism analysis can differentiate between gestational vs. nongestational choriocarcinoma, as latter exclusively has maternal alleles (Int J Gynecol Pathol 2012;31:364)
Differential diagnosis
  • Epithelial trophoblastic tumor: uniform nested population of intermediate trophoblastic cells, extensive necrosis, hyaline matrix with a geographic configuration
  • Nongestational choriocarcinoma: usually associated with mixed germ cell tumors (teratoma, embryonal carcinoma, yolk sac tumor) and endometrioid adenocarcinoma
  • Noninvasive or invasive hydatidiform mole: presence of chorionic villi
  • Placental site trophoblastic tumor: lack of a trimorphic population of trophoblasts; low hCG, paucity of hemorrhage and the presence of an interdigitating pattern of muscle invasion; Ki67 is low (10 - 30%)
Board review style question #1
FIGO / WHO prognostic scoring system of gestational trophoblastic disease includes all, except:

  1. Age
  2. Genetic profile
  3. hCG levels
  4. Site of tumor
  5. Size of tumor
Board review style answer #1
B. Genetic profile

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