Choriocarcinoma

Gynecological Oncology

Clinicals - History

Fact Explanation
Previous history of molar pregnancy and abortion Choriocarcinoma is a rare and highly malignant neoplasm of trophoblastic origin among the GTDs. This tumour is known for its association with molar pregnancy.Choriocarcinoma is associated with a high human chorionic gonadotrophin (HCG) level. It is preceded by several clinical conditions, it is observed that about 50% arise in molar pregnancies, 25% arise after previous abortions, 22.5% arise in normal pregnancies, and 2.5% arise subsequent to ectopic pregnancies.. Previous history of molar pregnancy and abortion
Choriocarcinoma is a rare and highly malignant neoplasm of trophoblastic origin among the GTDs. This tumour is known for its association with molar pregnancy.Choriocarcinoma is associated with a high human chorionic gonadotrophin (HCG) level. It is preceded by several clinical conditions, it is observed that about 50% arise in molar pregnancies, 25% arise after previous abortions, 22.5% arise in normal pregnancies, and 2.5% arise subsequent to ectopic pregnancies..
Risk of metastasis It has a rapid haematogenous spread to multiple organs.The favoured sites are the lung (94%), vagina (44%), liver (28%), and brain (28%), followed by the skin, gastrointestinal tract,kidney, breast, and bones.Approximately 30% of patients with choriocarcinoma show metastasis at the time of diagnosis.. Risk of metastasis
It has a rapid haematogenous spread to multiple organs.The favoured sites are the lung (94%), vagina (44%), liver (28%), and brain (28%), followed by the skin, gastrointestinal tract,kidney, breast, and bones.Approximately 30% of patients with choriocarcinoma show metastasis at the time of diagnosis..
Intraparenchymal bleeding Because choriocarcinomas are very vascular lesions and are often perfused by fragile vessels, as well as due to the tendency of trophoblastic cells to invade and erode vessel walls, they are frequently haemorrhagic. Thus, intraparenchymal bleeding in any woman of child-bearing age with this malignancy is well explained.. Intraparenchymal bleeding
Because choriocarcinomas are very vascular lesions and are often perfused by fragile vessels, as well as due to the tendency of trophoblastic cells to invade and erode vessel walls, they are frequently haemorrhagic. Thus, intraparenchymal bleeding in any woman of child-bearing age with this malignancy is well explained..
Intra cerebral bleeding There are cases of choriocarcinoma presenting as intra cerebral bleed with aneurysmal dilatation. The proposed pathogenesis is not clearly understood but is probably due to the involvement of vessels because of the higher affinity of these malignant cells for blood vessels.. Intra cerebral bleeding
There are cases of choriocarcinoma presenting as intra cerebral bleed with aneurysmal dilatation. The proposed pathogenesis is not clearly understood but is probably due to the involvement of vessels because of the higher affinity of these malignant cells for blood vessels..
Torrential vaginal bleeding The second common site of hematogenous dissemination is vagina. Hypervascular metastases may present with features of hemorrhage. Vaginal metastases may result in torrential vaginal bleeding. Hence, a biopsy should be avoided.. Torrential vaginal bleeding
The second common site of hematogenous dissemination is vagina. Hypervascular metastases may present with features of hemorrhage. Vaginal metastases may result in torrential vaginal bleeding. Hence, a biopsy should be avoided..
Hemoptysis Most common site of hematogenous spread is lung.Lung metastases may be asymptomatic or present with hemoptysis.. Hemoptysis
Most common site of hematogenous spread is lung.Lung metastases may be asymptomatic or present with hemoptysis..
Dyspnea Resulted due to lung metastases.. Dyspnea
Resulted due to lung metastases..
Chest pain Also occurred due to lung metastases.. It will cause a pleuritic type chest pain.. Chest pain
Also occurred due to lung metastases.. It will cause a pleuritic type chest pain..
Headache Brian metastasis also can occur. Brain metastases may present with headache.. Headache
Brian metastasis also can occur. Brain metastases may present with headache..
Seizures Also occurs due to brain metastases.. The rapid onset of neurological signs related to bleeding in to necrotic tumour and compression of surrounding tissue is common. Jacksonian epilepsy from this cause and status epilepticus may occur.. Seizures
Also occurs due to brain metastases.. The rapid onset of neurological signs related to bleeding in to necrotic tumour and compression of surrounding tissue is common. Jacksonian epilepsy from this cause and status epilepticus may occur..
Excessive vomiting Gestational trophoblastic disease is comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor.They cause elevation of β-hCG leading to excessive vomiting..Hyperemesis gravidarum is a common symptom in patients with hyperthyroidism resulted due to choriocarcinoma.. Excessive vomiting
Gestational trophoblastic disease is comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor.They cause elevation of β-hCG leading to excessive vomiting..Hyperemesis gravidarum is a common symptom in patients with hyperthyroidism resulted due to choriocarcinoma..
Intrauterine demise or neonatal death One of the potential fatal outcome of placental choriocarcinoma.Most of the infants born showed no evidence of disease after 1 year.. Intrauterine demise or neonatal death
One of the potential fatal outcome of placental choriocarcinoma.Most of the infants born showed no evidence of disease after 1 year..
Back pain Back pain occurs secondary to retroperitoneal spread.. Back pain
Back pain occurs secondary to retroperitoneal spread..
Cough The main symptoms in the patients with pulmonary presentations were haemoptysis, dyspnoea, pleuritic pain, and cough without haemoptysis.In the lungs distortion of the bronchial tree by metastases
may produce chronic non productive cough..
Cough
The main symptoms in the patients with pulmonary presentations were haemoptysis, dyspnoea, pleuritic pain, and cough without haemoptysis.In the lungs distortion of the bronchial tree by metastases
may produce chronic non productive cough..
Malena Malena can be resulted from metastases within the bowel.. Malena
Malena can be resulted from metastases within the bowel..
Deterioration of memory and disturbances of consciousness Clinical features produced by compression of surrounding
structures may be variable. Slowly growing intracranial tumours may give rise to headaches, deterioration of memory and intellect,disturbances of consciousness, and clinical signs of raised intracranial pressure..
Deterioration of memory and disturbances of consciousness
Clinical features produced by compression of surrounding
structures may be variable. Slowly growing intracranial tumours may give rise to headaches, deterioration of memory and intellect,disturbances of consciousness, and clinical signs of raised intracranial pressure..
Haematuria. Extension of the tumour into the surrounding parenchyma may occur. Infarction distal to the obstruction is common and may result in pleuritic pain, pleural effusion, haemoptysis, and haematuria.. Haematuria.
Extension of the tumour into the surrounding parenchyma may occur. Infarction distal to the obstruction is common and may result in pleuritic pain, pleural effusion, haemoptysis, and haematuria..
Disease recurrence Women with history of GTN have a potential risk of disease recurrence that is largely dependent on their initial stage. Recurrence rates is about 2% in patients with nonmetastatic GTN, 4% in patients with low-risk, metastatic GTN, and 13% in patients with high-risk, metastatic disease.. Disease recurrence
Women with history of GTN have a potential risk of disease recurrence that is largely dependent on their initial stage. Recurrence rates is about 2% in patients with nonmetastatic GTN, 4% in patients with low-risk, metastatic GTN, and 13% in patients with high-risk, metastatic disease..

Clinicals - Examination

Fact Explanation
Pulmonary artery hypertension Resulted due to lung metastases.. One form of obstructive vascular disease is that involving the pulmonary arteries, producing progressive pulmonary hypertension with its accompanying dyspnoea and sometimes chronic cough.. Pulmonary artery hypertension
Resulted due to lung metastases.. One form of obstructive vascular disease is that involving the pulmonary arteries, producing progressive pulmonary hypertension with its accompanying dyspnoea and sometimes chronic cough..
Motor, or sensory deficit A manifestation of brain metastasis.. Motor, or sensory deficit
A manifestation of brain metastasis..
Enlarged uterus Abnormally enlarged uterus can be found.. Abnormal masses in abdominal viscera can be found in some occasions.. Enlarged uterus
Abnormally enlarged uterus can be found.. Abnormal masses in abdominal viscera can be found in some occasions..
Hyperthyroidism They some times present with hyperthyroidism..The mechanism of the hyperthyroidism is probably due to the ability of HCG to stimulate the TSH receptors, as it has an identical alpha subunit to that of the TSH.. Hyperthyroidism
They some times present with hyperthyroidism..The mechanism of the hyperthyroidism is probably due to the ability of HCG to stimulate the TSH receptors, as it has an identical alpha subunit to that of the TSH..
Papilloedema Metastasis to the brain may occur.Raised intracranial pressure, frequently present with papilloedema and disturbances of consciousness.. Papilloedema
Metastasis to the brain may occur.Raised intracranial pressure, frequently present with papilloedema and disturbances of consciousness..
Hemiplegic syndrome and paraplegia Rapid onset of neurological signs related to bleeding into necrotic tumour and compression of surrounding tissue can occur.by far the commonest manifestation is a hemiplegic syndrome.Paraplegia from spinal cord involvement has been described as a presenting feature.. Hemiplegic syndrome and paraplegia
Rapid onset of neurological signs related to bleeding into necrotic tumour and compression of surrounding tissue can occur.by far the commonest manifestation is a hemiplegic syndrome.Paraplegia from spinal cord involvement has been described as a presenting feature..

Investigations - Diagnosis

Fact Explanation
Serum β-hCG Immunohistochemistry analysis is useful in differential diagnosis of choriocarcinoma. Strong diffuse β-hCG immunoreactivity confirms the diagnosis of choriocarcinoma.. However β-hCG levels are usually lower in nongestational variants in comparison to gestational types.. Serum β-hCG
Immunohistochemistry analysis is useful in differential diagnosis of choriocarcinoma. Strong diffuse β-hCG immunoreactivity confirms the diagnosis of choriocarcinoma.. However β-hCG levels are usually lower in nongestational variants in comparison to gestational types..
Tumor markers CD-30 is a member of the tumor necrosis factor superfamily of cytokine receptors. Positive staining for CD-30 has been used for diagnosis of embryonal carcinoma. OCT-3/4 and CD-30 can be used in combination to establish the germ cell origin of any metastatic tumor. Negative staining for both markers helps in ruling out a germ cell origin of such tumors.Various serum tumor markers (β-hCG, AFP and CA-125) are also useful in the differential diagnosis of choriocarcinoma.. Tumor markers
CD-30 is a member of the tumor necrosis factor superfamily of cytokine receptors. Positive staining for CD-30 has been used for diagnosis of embryonal carcinoma. OCT-3/4 and CD-30 can be used in combination to establish the germ cell origin of any metastatic tumor. Negative staining for both markers helps in ruling out a germ cell origin of such tumors.Various serum tumor markers (β-hCG, AFP and CA-125) are also useful in the differential diagnosis of choriocarcinoma..
DNA polymorphism analysis A search for paternal DNA in tumor allows a definite distinction between gestational and nongestational types. Tumors with gestational origin have paternal genomic structure while nongestational tumors have genomes of only maternal origin without any alleles from paternal origin.But DNA polymorphism analysis is not a generally available laboratory technique in most centers.. DNA polymorphism analysis
A search for paternal DNA in tumor allows a definite distinction between gestational and nongestational types. Tumors with gestational origin have paternal genomic structure while nongestational tumors have genomes of only maternal origin without any alleles from paternal origin.But DNA polymorphism analysis is not a generally available laboratory technique in most centers..
USS Invasive mole, choriocarcinoma, and PSTT are seen on grey-scale ultrasound as nonspecific focal masses with myometrial epicenter and are sonographically indistinguishable from one another. The mass may be echogenic, hypoechoic, complex, or multicystic. It may show anechoic spaces which represent hemorrhage, necrosis, cysts, or vascular spaces. More extensive disease may appear as a heterogeneously enlarged uterus with lobulated contour or large pelvic mass which may extend to involve other pelvic organ.. USS
Invasive mole, choriocarcinoma, and PSTT are seen on grey-scale ultrasound as nonspecific focal masses with myometrial epicenter and are sonographically indistinguishable from one another. The mass may be echogenic, hypoechoic, complex, or multicystic. It may show anechoic spaces which represent hemorrhage, necrosis, cysts, or vascular spaces. More extensive disease may appear as a heterogeneously enlarged uterus with lobulated contour or large pelvic mass which may extend to involve other pelvic organ..
Doppler ultrasound Color flow and spectral Doppler are routinely performed in addition to grey-scale ultrasound for diagnosis of the primary or recurrent GTD and post treatment follow-up.lower resistive indices (RI) seen in invasive mole and choriocarcinoma than complete or partial hydatiform mole indicative of greater degree of vascular invasion in the first two.. Doppler ultrasound
Color flow and spectral Doppler are routinely performed in addition to grey-scale ultrasound for diagnosis of the primary or recurrent GTD and post treatment follow-up.lower resistive indices (RI) seen in invasive mole and choriocarcinoma than complete or partial hydatiform mole indicative of greater degree of vascular invasion in the first two..
Computed Tomography (CT) CT is principally used for detection of metastatic disease. CT can also identify vascular malformations resulting from GTN.. Computed Tomography (CT)
CT is principally used for detection of metastatic disease. CT can also identify vascular malformations resulting from GTN..
Magnetic Resonance Imaging (MRI) MRI does not have a role in routine assessment of pelvic disease. It is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases, suspected PSTT, and recurrent GTN.. Magnetic Resonance Imaging (MRI)
MRI does not have a role in routine assessment of pelvic disease. It is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases, suspected PSTT, and recurrent GTN..
Conventional Angiography Although color Doppler ultrasound is the modality of choice for diagnosing uterine vascular malformations, angiography is the Preferred method in patients who may potentially undergo embolization for management of the vascular malformations persisting despite complete response to chemotherapy and complicated by refractory, life threatening vaginal, or intraperitoneal hemorrhage.. Conventional Angiography
Although color Doppler ultrasound is the modality of choice for diagnosing uterine vascular malformations, angiography is the Preferred method in patients who may potentially undergo embolization for management of the vascular malformations persisting despite complete response to chemotherapy and complicated by refractory, life threatening vaginal, or intraperitoneal hemorrhage..

Investigations - Management

Fact Explanation
Serial serum β-hCG levels All choriocarcinomas secrete hCG, which can be useful for monitoring the patient's response to treatment. Serum β-hCG should be determined weekly during treatment, then every 2 weeks for 3 months, then monthly for next 3 months, and then every 2 months for the next 6 months. If the treatment fails to elicit a continued fall in β-hCG titers, or if disease recurs after cessation of chemotherapy, then the patient should be reevaluated, and therapy different from that previously employed should be initiated. Alternatively, if the β-hCG level reaches an undetectable level, treatment should be continued for two more courses in the case of gestational disease.. Serial serum β-hCG levels
All choriocarcinomas secrete hCG, which can be useful for monitoring the patient's response to treatment. Serum β-hCG should be determined weekly during treatment, then every 2 weeks for 3 months, then monthly for next 3 months, and then every 2 months for the next 6 months. If the treatment fails to elicit a continued fall in β-hCG titers, or if disease recurs after cessation of chemotherapy, then the patient should be reevaluated, and therapy different from that previously employed should be initiated. Alternatively, if the β-hCG level reaches an undetectable level, treatment should be continued for two more courses in the case of gestational disease..
Preoperative imaging studies Preoperative imaging studies such as ultrasound, MRI, arteriography, and positron emission tomography (PET) scans may be helpful in identifying the site of residual tumor and can, therefore, facilitate surgical planning.. Preoperative imaging studies
Preoperative imaging studies such as ultrasound, MRI, arteriography, and positron emission tomography (PET) scans may be helpful in identifying the site of residual tumor and can, therefore, facilitate surgical planning..

Management - Supportive

Fact Explanation
Chemotherapy Multi agent chemotherapy is the treatment of choice in high-risk choriocarcinoma. Currently, the most widely used combination regime is EMACO. However, 14% of the high-risk patients who received the EMACO chemotherapy as well as 1% of the low-risk patients who initially received methotrexate followed by the EMACO regimen require further treatment..Gestational choriocarcinoma is highly sensitive to chemotherapy, that arising from the testis and ovary is less so but the mortality due to choriocarcinoma in males has fallen from 70% to 20% after the introduction of chemotherapy. Principally using actinomycin D, methotrexate, cyclophosphamide, and recently, etoposide. The treatment of choriocarcinoma with cerebral metastases involves chemotherapy in conjunction with cranial irradiation.. Patients with stage I and low-risk stage II and III GTN (FIGO prognostic score of ≤6) generally respond well to single agent chemotherapy.But with an hCG value exceeding 100,000 mIU/mL frequently require combination chemotherapy. Patients with stage II or III GTN and an FIGO prognostic score ≥7 have a high-risk disease and are unlikely to be cured with single-agent therapy. Therefore, they should be treated with combination chemotherapy [.3]. Chemotherapy
Multi agent chemotherapy is the treatment of choice in high-risk choriocarcinoma. Currently, the most widely used combination regime is EMACO. However, 14% of the high-risk patients who received the EMACO chemotherapy as well as 1% of the low-risk patients who initially received methotrexate followed by the EMACO regimen require further treatment..Gestational choriocarcinoma is highly sensitive to chemotherapy, that arising from the testis and ovary is less so but the mortality due to choriocarcinoma in males has fallen from 70% to 20% after the introduction of chemotherapy. Principally using actinomycin D, methotrexate, cyclophosphamide, and recently, etoposide. The treatment of choriocarcinoma with cerebral metastases involves chemotherapy in conjunction with cranial irradiation.. Patients with stage I and low-risk stage II and III GTN (FIGO prognostic score of ≤6) generally respond well to single agent chemotherapy.But with an hCG value exceeding 100,000 mIU/mL frequently require combination chemotherapy. Patients with stage II or III GTN and an FIGO prognostic score ≥7 have a high-risk disease and are unlikely to be cured with single-agent therapy. Therefore, they should be treated with combination chemotherapy [.3].
Hysterectomy In women who no longer desire fertility, a hysterectomy may be considered in stage I disease to decrease exposure to multiple doses of chemotherapeutic agents. In this treatment strategy, the patient receives one course of single-agent chemotherapy at the time of surgery. This is imperative to treat occult metastases that may be present at the time of surgery, to reduce the likelihood of disseminating viable tumor cells during surgery, and to maintain a cytotoxic level of chemotherapy in the blood and tissues in case viable tumor cells are disseminated during surgery.. Hysterectomy
In women who no longer desire fertility, a hysterectomy may be considered in stage I disease to decrease exposure to multiple doses of chemotherapeutic agents. In this treatment strategy, the patient receives one course of single-agent chemotherapy at the time of surgery. This is imperative to treat occult metastases that may be present at the time of surgery, to reduce the likelihood of disseminating viable tumor cells during surgery, and to maintain a cytotoxic level of chemotherapy in the blood and tissues in case viable tumor cells are disseminated during surgery..
Local uterine resection of the tumor mass If a large tumor volume is identified within the uterus, a hysterectomy may be performed to remove the focus of drug resistance. If the woman desires to retain her fertility, local uterine resection of the tumor mass can be attempted. This management option should be reserved for carefully selected patients. Women should be counseled about the potential future obstetrical risks associated with this procedure, including uterine rupture.. Local uterine resection of the tumor mass
If a large tumor volume is identified within the uterus, a hysterectomy may be performed to remove the focus of drug resistance. If the woman desires to retain her fertility, local uterine resection of the tumor mass can be attempted. This management option should be reserved for carefully selected patients. Women should be counseled about the potential future obstetrical risks associated with this procedure, including uterine rupture..
Vaginal packing and/or wide local excision Vaginal metastases are often highly vascular and friable and may bleed profusely. Bleeding is often controlled by packing the vagina. However, other modalities may become necessary such as wide local excision of the lesions or angiographic embolization of the hypogastric vessels.. Vaginal packing and/or wide local excision
Vaginal metastases are often highly vascular and friable and may bleed profusely. Bleeding is often controlled by packing the vagina. However, other modalities may become necessary such as wide local excision of the lesions or angiographic embolization of the hypogastric vessels..

Management - Specific

Fact Explanation
Thoracotomy An interesting procedure in the management of stage III GTN is thoracotomy, which has a limited yet important role in the management of lung metastases. Thoracotomy can be useful to establish the diagnosis of GTN if the diagnosis cannot be clarified using less invasive measures. In addition, in patients with persistent, viable pulmonary nodules that are resistant to chemotherapy, pulmonary resection may be curative.. Thoracotomy
An interesting procedure in the management of stage III GTN is thoracotomy, which has a limited yet important role in the management of lung metastases. Thoracotomy can be useful to establish the diagnosis of GTN if the diagnosis cannot be clarified using less invasive measures. In addition, in patients with persistent, viable pulmonary nodules that are resistant to chemotherapy, pulmonary resection may be curative..
Craniotomy Craniotomy is performed to relieve intracranial pressure.. However surgery is associated with a high incidence of haemorrhagic complications and should only be performed if the haemorrhage itself is life threatening. . Craniotomy
Craniotomy is performed to relieve intracranial pressure.. However surgery is associated with a high incidence of haemorrhagic complications and should only be performed if the haemorrhage itself is life threatening. .
Angiographic uterine embolization In patients who are hemodynamically stable, angiographic uterine embolization can be effective in the management of uterine bleeding, especially in women who wish to retain their fertility.. Angiographic uterine embolization
In patients who are hemodynamically stable, angiographic uterine embolization can be effective in the management of uterine bleeding, especially in women who wish to retain their fertility..
Hepatic resection The management of complications from hepatic metastases can be particularly challenging in patients with advanced GTN. In rare instances, hepatic resection may be required to control bleeding.. Hepatic resection
The management of complications from hepatic metastases can be particularly challenging in patients with advanced GTN. In rare instances, hepatic resection may be required to control bleeding..

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