Placenta
Gestational trophoblastic disease
Choriocarcinoma
Authors: Sonali Lanjewar, M.B.B.S., Raavi Gupta, M.D.
Topic Completed: 1 February 2017
Minor changes: 10 December 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed search: Gestational choriocarcinoma placenta [title]
Table of Contents
Essential features | Epidemiology | Risk factors | Clinical features | Laboratory | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review answer #1Cite this page: Lanjewar S, Gupta R. Choriocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/placentachoriocarcinoma.html. Accessed August 7th, 2020.
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
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 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
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;83:175, PDF)
Case reports
- Newborn with infantile choriocarcinoma (Arch Pediatr 2005;12:1721)
- 28 year old woman with intraplacental choriocarcinoma arising in a second trimester placenta with partial hydatidiform mole (Int J Gynecol Pathol 2008;27:247)
- 69 year old man with primary gastric choriocarcinoma (Int J Surg Case Rep 2015;14:44)
Treatment
- Based on FIGO / WHO prognostic score (Int J Gynaecol Obstet 2003;83:175, ISSTD: The FIGO 2002 Staging and Risk Factor Scoring System for Gestational Trophoblastic Disease [Accessed 20 October 2017]), 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
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
- 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:
- Age
- Genetic profile
- hCG levels
- Site of tumor
- Size of tumor
Board review answer #1
