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Choriocarcinoma

Choriocarcinomas


Presentation

Choriocarcinoma may present with the following symptomatology in patients:

  • First trimester bleeding (bright red to brown in color)
  • Severe nausea and vomiting due to increase beta-hCG in the serum
  • Passage of grape-like cysts per vagina (Hydatidiform mole preceding choriocarcinoma)
  • Pelvic pressure pains due to rapidly enlarging conceptus
  • Disproportionate growth of the uterus (as compared to actual age of gestation)
  • Pre-eclampsia and high blood pressure due to the constricting chorionic villi
  • Ovarian cyst forms with the hormonal imbalance states 
  • Anemia due to chronic uterine hemorrhage 
  • Acquired hyperthyroidism due to the hypothalamic-pituitary feedback disarray
Red Eye
  • CASE REPORT: A 23-year-old woman presented to our Emergency Department with a left painful red eye with decreased visual acuity and was subsequently diagnosed with choriocarcinoma with metastasis to the lungs, brain, and choroid, causing a left exudative[ncbi.nlm.nih.gov]
Neck Mass
  • Findings on an incisional biopsy of the neck mass were consistent with a choriocarcinoma. The testicles were normal on palpation and ultrasonography.[ncbi.nlm.nih.gov]
Pelvic Pain
  • Cause Chromosomal mutation and aneuploidy, and history of previous molar pregnancy Symptoms Vaginal bleeding, rapidly enlarging uterus, pelvic pain, anemia, and hypertension may occur.[symptoma.com]
  • . • Pelvic pain or pressure –If an enlarged uterus or ovarian cysts are present, the patient may report pelvic pain or pressure 30.[slideshare.net]
  • Other symptoms can include regular pregnancy symptoms, menstrual or pelvic pain, increased or high b-hcg levels, coughing, shortness of breath, dizziness, blurred vision, headaches and even seizures.[themighty.com]
  • It is particularly challenging to differentiate choriocarcinoma from the more common ectopic pregnancy in a young woman who has a positive result of a pregnancy test, pelvic pain, and an adnexal mass.[ajronline.org]
Metrorrhagia
  • The first one was manifested by neurological deterioration as the first sign of metastasis, while the second patient had firstly metrorrhagia and in the further couse neurological disturbances that suggested the presence of brain tumor.[ncbi.nlm.nih.gov]
  • metrorrhagia following spontaneous abortion or VTP, occasionally unexplained metrorrhagia in the weeks or months following normal childbirth or an ectopic pregnancy.[orpha.net]
  • We report the case of a patient who presented to the emergency department referring little metrorrhagia from a normal delivery two months ago and severe bleeding later during her hospital stay.[scielo.conicyt.cl]

Workup

The following diagnostic workups are performed in patients with choriocarcinoma and other gestational trophoblastic diseases:

  • Blood test: The serum determination of hCG is useful test in determining the presence of any GTD in the uterus. This may be used to prognosticate and manage cases of choriocarcinoma.
  • Pelvic ultrasound: In early pregnancy, a transvaginal probe may be used while those in midterm pregnancy may benefit from abdominal probes. Sonographic findings in GTD include: the absence of a fetus, oligohydramnios, presence of ovarian cysts and cystic placenta filling the uterus. 
  • Hypertensive and thyroid workup: Patients diagnosed with Choriocarcinoma and molar pregnancies usually presents with a concomitant hypertension and hyperthyroidism. The medical stabilization of these complications may lower the morbidity rate among patients.
Toxoplasma Gondii
  • BACKGROUND: Toxoplasma gondii, a single-celled parasite commonly found in mammals, has been shown to induce trophoblast cell apoptosis and subsequently cause fetal damage and abortion.[ncbi.nlm.nih.gov]
Trophoblastic Cells
  • Additionally, in the trophoblastic cell line Swan71, we found a significant induction of RARRES1 expression with increased cell density, during mitosis and in syncytial knots.[ncbi.nlm.nih.gov]
  • Expression of miR-21 in trophoblast cells and tissues was examined by quantitative real-time polymerase chain reaction.[ncbi.nlm.nih.gov]
  • […] choriocarcinoma (kor″e-o-kahr″sĭ-no�mә) a malignant neoplasm of trophoblastic cells formed by abnormal proliferation of the placental epithelium, without production of chorionic villi.[web.archive.org]
  • Immunohistochemistry showed that Griffonia simplicifolia lectin-II staining and GnT-IVa staining were intense in trophoblastic cells of invasive mole and choriocarcinoma.[ncbi.nlm.nih.gov]
  • In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways.[ncbi.nlm.nih.gov]

Treatment

The following treatment modalities are available in the treatment of choriocarcinoma:

  • Dilatation and Curettage (D and C): Hydatidiform moles as a choriocarcinoma precursor is usually removed by D and C as soon as it is diagnosed to prevent its complications.
  • Total hysterectomy: When gestational trophoblastic tumors are diagnosed and there are no further plans of conceiving, the patient and the doctor may opt to remove the whole uterus to prevent further complications.
  • Chemotherapy: Metastatic forms of choriocarcinoma may benefit with chemotherapeutic agents like methotrexate and actinomycin that retards the growth and spread of the cancer [10]. 

Prognosis

Patient diagnosed with metastatic choriocarcinoma is considered high risk and has a grim prognostic outlook [7]. Other parameters seen in choriocarcinoma which is considered high risk include: brain and liver metastasis, serum human Chorionic Gonadotropin (hCG) level of more than 40,000 mlU/ml, disease duration of more than 4 months, previous history of unsuccessful chemotherapy, and malignant choriocarcinoma following a term pregnancy.

Chemotherapy has a success rate of 75% in the treatment of high risk malignant gestational trophoblastic neoplasia with metastasis [8]. The probability of late recurrence in choriocarcinoma approaches 1% after a year of remission from chometherapy [9].

Complications

The following complications are commonly seen in cases of Choriocarcinoma:

Etiology

Choriocarcinoma and the other gestational trophoblastic diseases are caused by an abnormally fertilized egg. In a complete molar pregnancy, all of the fertilized egg chromosomes are derived from the father. The mother’s chromosomes in the egg are lost shortly after fertilization and the father’s chromosome is duplicated resulting to an egg an inactive nucleus or no nucleus at all. In cases of partial and incomplete molar pregnancies, the father provides a duplicate set of chromosomes while the chromosome set from the mother remains. This will result in an embryo with 69 chromosomes instead of 46. Such etiology usually happens when two sperms fertilize a single egg in the uterus.

Epidemiology

In the United States, gestational trophoblastic neoplasia (GTN) occurs in 15-20% of patients with a complete hydatidiform mole and only 2% from incomplete hydatidiform mole. The relative incidence of choriocarcinoma is 1 out of 40 hydatidiform molar pregnancies [1].

The pregnancy prevalence of choriocarcinoma is about 1 in 20,000 to 40,000 pregnancies [2]. However, choriocarcinoma incidence plunges to 1 out of 160,000 after a successful term pregnancy [3].

The relative prevalence of choriocarcinoma with any molar pregnancy and other GTD’s vary in every region of the globe. An increased prevalence rate of 1 in 500-600 pregnancies are observed in India [4] while a 1 in 50,000 pregnancy ratio is seen in Mexico, Paraguay and Sweden [5].

Sex distribution
Age distribution

Pathophysiology

Choriocarcinoma starts as an aneuploidy of the chromosome set which can be heterozygous depending on the type pregnancy origin. Chromosomes may appear exclusively paternal in origin if the choriocarcinoma is preceded by a molar pregnancy. Majority of choriocarcinoma is virtually preceded by a hydatidiform mole pregnancy in up to 50% of the cases. However, both paternal and maternal sets of chromosomes are present in the choriocarcinoma if it follows a term pregnancy.

The condition may also follow an ectopic pregnancy in a relative ratio of 1 is to 5,333 ectopic pregnancies [6].

Prevention

The incidence of choriocarcinoma increases significantly when the woman reaches the age of 40 years old; thus, it is prudent to avoid conceiving during this age to prevent this gestational tumor.

Women with previous history of a molar pregnancy should wait for six to twelve months before planning another conception to lower the risk given that choriocarcinoma stems out from molar pregnancies in 50% of the time. Careful monthly ultrasound monitoring of the fetus may be advised for those mothers with prior GTD histories.

Summary

Choriocarcinoma is a clinical disease described as the most aggressive form of gestational trophoblastic disease (GTD) characterized by rapid growth and a high metastatic potential. Choriocarcinoma is a cancer that originates from the trophoblast which surrounds the blastocyst. This aggressive tumor may occur during and after intrauterine pregnancy and ectopic pregnancy. When choriocarcinoma occurs during pregnancy, spontaneous abortions, preeclampsia and fetal death usually ensues with a very rare instance of fetal survival. Some forms of GTD are discovered malignant while others are benign although they may behave aggressively.

When choriocarcinoma develops in the absence of preceding gestation, it is referred to as non-gestational choriocarcinoma. These occur most often in the ovary or testes, but are very rare. It is important to distinguish the different forms because of the poor prognosis of non-gestational choriocarcinoma.

Patient Information

Definition

Choriocarcinoma is an aggressive form of gestational trophoblastic disease (GTD) characterized by rapid tumor growth and a high metastatic potential.

Cause

Chromosomal mutation and aneuploidy, and history of previous molar pregnancy

Symptoms

Vaginal bleeding, rapidly enlarging uterus, pelvic pain, anemia, and hypertension may occur.

Diagnosis

Blood tests and abdominal and transvaginal ultrasound are done to diagnose choriocarcinoma.

Treatment and follow-up

Dilatation and Curettage, hysterectomy and chemotherapy are the most common treatment options.

References

Article

  1. Smith HO, Kohorn E, Cole LA. Choriocarcinoma and gestational trophoblastic disease. Obstet Gynecol Clin North Am. Dec 2005; 32(4):661-84.
  2. Grimes DA. Epidemiology of gestational trophoblastic disease. Am J Obstet Gynecol. Oct 1 1984; 150(3):309-18.
  3. McDonald TW, Ruffolo EH. Modern management of gestational trophoblastic disease. Obstet Gynecol Surv. Feb 1983; 38(2):67-83.
  4. Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med. Mar 1994; 39(3):155-62.
  5. Chakrabarti BK, Mondal NR, Chatterjee T. Gestational trophoblastic tumor at a tertiary level cancer center: a retrospective study. J Reprod Med. Nov 2006; 51(11):875-8.
  6. Lurain JR, Sand PK, Brewer JI. Choriocarcinoma associated with ectopic pregnancy. Obstet Gynecol. Aug 1986; 68(2):286-7.
  7. Soper JT. Gestational trophoblastic disease. Obstet Gynecol. Jul 2006; 108(1):176-87.
  8. Soper JT, Evans AC, Conaway MR, et al. Evaluation of prognostic factors and staging in gestational trophoblastic tumor. Obstet Gynecol. Dec 1994; 84(6):969-73.
  9. Mutch DG, Soper JT, Babcock CJ, et al. Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer. Sep 1 1990; 66(5):978-82.
  10. Ngan HY, Odicino F, Maisonneuve P, Creasman WT, Beller U, Quinn MA, et al. Gestational trophoblastic neoplasia. FIGO 6th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. Nov 2006; 95 Suppl 1:S193-203.

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Last updated: 2018-06-22 09:45