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Choriocarcinoma
Choriocarcinomas

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WIKIDATA, CC BY-SA 3.0
WIKIDATA, CC BY-SA 3.0
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WIKIDATA, CC BY-SA 4.0
WIKIDATA, CC BY-SA 4.0
WIKIDATA, CC BY-SA 4.0

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

Entire Body System

  • Pain

    Back pain Back pain occurs secondary to retroperitoneal spread.[4]. [explainmedicine.com]

    A 58-year-old female with intermittent back pain was referred to a private hospital. On examination, a mediastinal tumor and a pancreatic tumor were detected. [ncbi.nlm.nih.gov]

    Comfort Cool Tennis Elbow Braces - Elbow Wraps, Sleeves & Bands Finger - Thumb Supports Foot and Ankle Braces - Supports Foot Pain & Injury Hernia Aids and Support Hip Surgery and Injury Knee Braces & Support Orthopedic Back Cushions Orthopedic Pillows [activeforever.com]

  • Anemia

    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]

    This disease caused neonatal anemia but did not metastasize to either the mother or infant. Short tandem repeat analysis with laser microdissection revealed that the tumor had originated from the current pregnancy. [ncbi.nlm.nih.gov]

    These cases present with vaginal bleeding, anemia, hyperemesis gravidarum, hyperthyroidism, uterine and ovarian enlargement, and pregnancy-induced hypertension. [ccij-online.org]

  • Falling

    When β-hCG levels do not fall appropriately in women undergoing medical management for pregnancy of unknown location, ectopic β-hCG secretion by a malignancy must be considered. [ncbi.nlm.nih.gov]

    Everything was going great and seemed to be falling into place. They were so excited to be parents. Throughout the pregnancy there were no issues. But on December 1, 2014 Lauren noticed that Dylan wasn't moving. [gofundme.com]

    Pain Relief Parkinsons Pediatrics & Maternity Physical Therapy Skin Care Winter Products Oxygen Hospital Supplies Shop by Topic Arthritis Pain Relief Assistive Technology Care for Your Feet Carpal Tunnel Syndrome Diet and Nutrition Emergency Supplies Fall [activeforever.com]

    He was devastated to see my eyelashes and eyebrows fall out. The anxiety of this journey and being away from my children was just unbearable. [themighty.com]

  • Epilepsy

    Abstract Gabapentin (GBP) is a widely used antiepileptic drug, with potential for use in the treatment of epilepsy in pregnant women. [ncbi.nlm.nih.gov]

    Jacksonian epilepsy from this cause and status epilepticus may occur.[5]. [explainmedicine.com]

    […] diagnostic tests, consultations with fee-approved specialists and specialist treatment – including radiotherapy and chemotherapy What you're not covered for Chronic conditions We cannot cover incurable long-term illnesses such as diabetes, arthritis, epilepsy [aviva.co.uk]

  • Pallor

    Patient was thin built, vitals were normal, mild pallor with no evidence of any other abnormality found on general examination. Her systemic examination revealed normal findings of cardiovascular and respiratory system. [ccij-online.org]

    Signs –Patient looks ill –Features of shock, pallor –Features of thyrotoxicosis, enlarged thyroid gland –Uterine size may not correspond to period of amenorrhea –Uterus may feel firm elastic, doughy(absence of amniotic fluid sac) –Absent fetal heart sound [slideshare.net]

Gastrointestinal

  • Abdominal Mass

    An abdominal mass was found and resected. Pathology reported an ovaric mixed germ cell tumor with coriocarcinoma and dysgerminoma. [scielo.org.mx]

    • Varying degree of lower abdominal pain • Abdominal mass • Respiratory symptoms: dyspnoea haemoptysis • Features of hyperthyroidism: tremor palpitation. • Expulsion of grapes like vesicles(diagnostic) • Past history of molar pregnancy 9. B. [slideshare.net]

    Figure 1 A CT scan of the abdomen demonstrated a 6 cm mass (T) in the pancreas. Physical examination revealed a well-nourished man with jaundice, but no peripheral adenopathy or palpable abdominal mass. [nature.com]

  • Failure to Thrive

    Typical early symptoms of decreasing incidence are anemia, failure to thrive, hepatomegaly, hemoptysis or respiratory failure; there may be signs of precocious puberty. [omicsonline.org]

Cardiovascular

  • Hypotension

    Seven days after admission the patient presented melaena and hypotension, which required blood transfusion. Endoscopy showed a 3 cm submucosal mass with a central deep ulceration in the upper body of the stomach, but no blood was found. [scielo.isciii.es]

  • Heart Disease

    Abstract Cigarette smoke (CS) causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. [ncbi.nlm.nih.gov]

Skin

  • Alopecia

    All the patients had nausea, vomiting, anorexia; three developed alopecia. Bone marrow depression occurred in one patient. No other adverse effects were seen (Table-7). [ayubmed.edu.pk]

    Complications Complications of choriocarcinoma is primarily related to the complications of chemotherapy such as alopecia or hair loss, anorexia, muscle wasting, weight loss, nausea and vomiting and high risk for infection. [cancerwall.com]

    Treatment with methotrexate is more tolerable than treatment with EMA-CO, which can be associated with alopecia, nausea, vomiting, rash, and neutropenia ( Lurain, 2011 ). [nursingcenter.com]

Neurologic

  • Seizure

    Two weeks later, she had another seizure. An angiogram showed an unruptured pseudoaneurysm along the right posterior cerebral artery, which was embolized. [ncbi.nlm.nih.gov]

    If it spreads to your brain, it may cause headaches or seizures. Chemotherapy is used to treat choriocarcinoma and usually successfully cures it. [nhs.uk]

    […] embolus, subdural hematoma and also as an arteriovenous malformation bleed. 5,6 Case Report A twenty-two year-old unmarried female presented to the casualty with a four-hour history of sudden, severe headache associated with vomiting and generalized seizure [ispub.com]

    Seizures Also occurs due to brain metastases.[2]. The rapid onset of neurological signs related to bleeding in to necrotic tumour and compression of surrounding tissue is common. [explainmedicine.com]

  • Asthenia

    Clinical case We present a clinical case where a 25-year-old male with no significant medical background was admitted showing asthenia, adinamy, general discomfort, hiporexy, dizziness, palpitations, dyspnea, melenic stool and a six kilo weight loss within [scielo.isciii.es]

Urogenital

  • Vaginal Bleeding

    A 31-year-old multigravida woman at 27 weeks' gestation was admitted with vaginal bleeding and a hypervascular mass near the cervix on 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]

    Symptoms A woman with an hydatidiform mole (partial or complete) or choriocarcinoma may experience one or more of these symptoms: irregular, non-menstrual vaginal bleeding, possibly with blood clots or a watery brown discharge pelvic pain or discomfort [mskcc.org]

    […] 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]

    The physical examination was remarkable only for severe right adnexal pain and tenderness. The patient underwent a pelvic sonographic examination for a possible ectopic pregnancy. [doi.org]

  • Cesarean Section

    After discharge with improvement, she was readmitted the next day for uncontrolled, heavy vaginal bleeding and underwent emergency cesarean section at 29 weeks' gestation. [ncbi.nlm.nih.gov]

    A cesarean section is preferably scheduled and treatment with chemotherapy is initiated. Choriocarcinoma is a tumor very sensitive to chemotherapy and has a high survival rate, although in metastatic cases the disease is usually fatal. [pubmed.ncbi.nlm.nih.gov]

    In this paper we report the case of a 40-year-old woman, gesta 2, para 2, presenting with a cervical well vascularized mass causing vaginal bleeding two years after the delivery of her second baby at term by cesarean section. [medichub.ro]

  • Metrorrhagia

    metrorrhagia following spontaneous abortion or VTP, occasionally unexplained metrorrhagia in the weeks or months following normal childbirth or an ectopic pregnancy. [orpha.net]

    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]

    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]

    We present the case of a 22-year-old nulliparous woman who spontaneously presents metrorrhagia with hemoptysis in the course of pregnancy at the 34th week. [pubmed.ncbi.nlm.nih.gov]

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.

Serum

  • Beta-HCG Increased

    If the blood level of beta-HCG increases or does not go down to normal, more tests will be done to see whether the tumor has spread. [theoncologyinstitute.com]

Other Pathologies

  • 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]

    Thymus ICD-O-3 topography code: C37 ICD10: C37 An aggressive malignant tumour arising from trophoblastic cells. The vast majority of cases arise in the uterus and represent gestational choriocarcinomas that derive from placental trophoblastic cells. [codes.iarc.fr]

    Also called gestational trophoblastic disease, gestational trophoblastic neoplasia, gestational trophoblastic tumor, or molar pregnancy. An aggressive malignant tumor arising from trophoblastic cells. [icd9data.com]

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:

  • Persistent gestational trophoblastic disease
  • Uterine bleeding
  • Persistently high hCG levels (causes confusion for pregnancy tests)
  • Organ metastasis
  • Anemia
  • Hyperthyroidism
  • Pregnancy-induced hypertension (preeclampsia and eclampsia)
  • Death

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].

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

  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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