Placenta
Gestational trophoblastic disease
Choriocarcinoma

Author: Sonali Lanjewar, M.D. (see Authors page)
Editor: Ravi Gupta, M.D.

Revised: April 21 2017, last major update February 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed search: gestational choriocarcinoma placenta

Cite this page: Choriocarcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/placentachoriocarcinoma.html. Accessed September 19th, 2017.
Essential features
  • A 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
Epidemiology
  • 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 1000 times more risk of developing choriocarcinoma than any other pregnancy event
  • Women of Asian, American Indian descent 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
  • The 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
  • The detection of ovarian theca ­lutein cysts long after a case of choriocarcinoma has been treated may indicate persistence of disease
Laboratory
  • 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 Suppl 1:175, PDF)
Case reports
Treatment
  • Based on FIGO / WHO prognostic score (Int J Gynaecol Obstet 2003;83 Suppl 1:175, PDF), patients are classified into low risk (≤ 6 score) and high risk (≥ 7)
    • Low risk: Single chemotherapeutic agent - Methotrexate or Actinomycin
    • High risk: Intensive combination chemotherapy
    • Cranial metastasis: Radiation therapy
  • Over 90% of patients are cured by treatment
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

Images hosted on PathOut server:

Contributed by Sonali Lanjewar, M.D.:

Arrow: syncytio-
trophoblast

Sheets of malignant
trophoblasts with
central hemorrhage
and necrosis

Long arrow: intermediate
trophoblasts; small arrow:
cytotrophoblasts



Images hosted on other servers:

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
  • An 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 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 answer #1
B. Genetic profile