Gestational trophoblastic neoplasia overview: Difference between revisions
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{{CMG}}{{AE}}{{ | {{Gestational trophoblastic neoplasia}} | ||
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==Overview== | |||
[[Gestational trophoblastic disease|Gestational trophoblastic disease (GTD)]] includes several rare [[Tumor|tumors]] that occur in the [[uterus]] and start in the [[Cell (biology)|cells]] that form the [[placenta]] during [[pregnancy]]. In 6th century, Aetius of Amida, a [[physician]] at Justinian's court came up with the term 'hydatid'. Next mention of 'mole' is from 1276 when Margaret, Countess of Henneberg, delivered approximately 300 babies on Good Friday (the Friday before Easter Sunday). In 1827, Marie Anne Victoire Boivin, a Parisian [[Midwifery|midwife]], proposed her findings of this condition in 'Nouvelles Recherches de la Mole Visiculaire' (News Searches of the Vesicular Mole). In 1840, William Wilton reported a case of invasive mole that was complicated by [[Uterine rupture|uterine]] [[perforation]] and fatal [[Internal bleeding|internal hemorrhage]]. In 1867, Richard von Volkmann, a German [[surgeon]], also described a [[lesion]] resembling an invasive mole. In 1877, Hans Chiari, an Austrian [[Pathology|pathologist]], reported three cases of choriocarcinoma. He recognized the [[Tumor|tumors]] as [[Epithelium|epithelial]]. In 1888, Max Sanger, a German [[Obstetrics|obstetrician]], proposed his [[theory]] that these [[Tumor|tumors]] were actually [[Sarcoma|sarcomas]] ('deciduoma malignum'). In 1890, Pfeiffer, a student of Hans Chiari, re-examined Chiari's cases and added a fourth case. He named them all 'deciduoma malignum'. In 1891, Pestalozza from Italy, reported three cases of a [[malignant]][[Uterus|uterine]] [[tumor]] associated with [[pregnancy]]. He described these cases as 'sarcoma hemorrhagicum sen infectiosum'. Gestational trophoblastic neoplasia may be classified according to [[histology]] into four subtypes: invasive mole, choriocarcinoma, placental-site trophoblastic[[ tumor]], and epithelioid trophoblastic tumor. [[Pregnancy]] occurs when an [[Ovum|egg]], which is released from the [[ovary]] during [[ovulation]], is fertilized by a [[sperm]]. Human [[pregnancy]] takes approximately 40 weeks. Gestational trophoblastic neoplasia arises from the [[Trophoblast|trophoblastic]] tissue, which provides nutrients to the [[embryo]] and develops into a large part of the [[placenta]]. Invasive mole is basically a [[benign]] [[tumor]] which arises from the invasion of the [[myometrium]] of a [[hydatidiform mole]]. Choriocarcinoma is a [[malignant]] [[tumor]] of the [[Trophoblast|trophoblastic]] [[epithelium]]. Placental-site trophoblastic tumor (PSTT), a rare [[tumor]], arises from the [[implantation]] site of [[placenta]]. Epithelioid trophoblastic tumor (ETT) is basically a rare variant of placental-site trophoblastic tumor (PSTT) which arises from the [[malignant]] transformation of [[Chorion|chorionic]]-type intermediate [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]]. Invasive mole is usually [[Ploidy|diploid]] but can also be [[Aneuploidy|aneuploid]] in [[Karyotype|karyotype.]] Choriocarcinoma has an [[Aneuploidy|aneuploid]][[karyotype]] and majority of the cases have a [[Y chromosome]]. [[Hydatidiform mole|Complete hydatidiform mole]] arises when an [[ovum]] without maternal [[Chromosome|chromosomes]] is [[Fertilization|fertilized]] by one [[sperm]] which duplicates its [[DNA]], resulting in a 46XX androgenetic [[karyotype]]. [[Hydatidiform mole|Partial hydatidiform moles]] are almost always [[Polyploidy|triploid]], resulting from the [[fertilization]] of a healthy [[ovum]] by two [[Sperm|sperms]]. Abnormal [[Trophoblast|trophoblastic]] population undergoing [[hyperplasia]] and [[anaplasia]] can give rise to choriocarcinoma. [[Gestation|Gestational]] type choriocarcinoma arises following a [[hydatidiform mole]], normal [[pregnancy]], or most commonly, abortion. Non-[[Gestation|gestational]] type choriocarcinoma arises from [[Pluripotency|pluripotent]] [[Germ cell|germ cells]]. [[Placenta|Placental]]-site [[Trophoblast|trophoblastic]] [[tumor]] (PSTT) arises from the [[Placenta|placental]] implantation site when the [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]] infiltrate the [[myometrium]]. [[Epithelioid]] [[Trophoblast|trophoblastic]] [[tumor]] (ETT) arises from the intermediate [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]] of [[chorion]].Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar [[symptoms]] and signs such as increase in [[uterine]] size, [[vaginal bleeding]] and [[amenorrhea]]. The differentials include [[molar pregnancy]] ([[Complete mole|complete]] and [[Molar pregnancy|partial moles]]), [[Ovarian tumor|ovarian tumors]], [[Spontaneous abortions|spontaneous abortion]], [[ectopic pregnancy]] and normal [[Pregnancy|term pregnancy]].The reported [[incidence]] of choriocarcinoma in the United States is 2 to 7 per 100,000 [[Pregnancy|pregnancies]]. The U.S. age-standardized (1960 World Population Standard) [[incidence]] rate of choriocarcinoma is approximately 0.18/100,000 women between the ages of 15 - 49 years. The [[prevalence]] of choriocarcinoma in the United States is 0.075 - 0.01 per 100, 000. The [[prevalence]] rates from Southeast Asia are 1.5 - 2.5 times higher. The 5-year overall [[mortality rate]], after the exclusion of [[Placenta|placental]] site [[Trophoblast|trophoblastic]] [[Tumor|tumors]] and [[epithelioid]] [[Trophoblast|trophoblastic]] [[Tumor|tumors]], is 2%. High-risk [[Patient|patients]] have a 5-year [[mortality rate]] of 12%. [[Patient|Patients]] with an [[International Federation of Gynecology and Obstetrics|International Federation of Gynecology and Obstetrics (FIGO)]] score of ≥13 have a 5-year [[mortality rate]] of 38.4%. The [[incidence]] of gestational trophoblastic neoplasia is higher in the extremes of [[Reproduction|reproductive]] ages. In Southasia, the [[incidence]] rates are double for Eurasians as compared to people of Chinese, Malaysian, or Indian origin. African Americans have a decreased [[incidence]] rate as compared to caucasians. The [[incidence]] is also higher in the Latin American population. Europe, North America, Australia, some areas of Latin America, and the Middle East have low [[incidence]] ratios.[[Symptoms]] of choriocarcinoma include [[vaginal bleeding]], passing of [[Tissue (biology)|tissue]] resembling a “bunch of grapes” from the vagina, and [[abdominal distention]]. Elevated serum [[human chorionic gonadotropin]] suggests diagnostic of choriocarcinoma.[[Chest radiography]] (CXR) may be helpful in the diagnosis of [[pulmonary]] [[metastasis]] of choriocarcinoma. The characteristic findings of [[pulmonary]] [[metastasis]] are peripheral, rounded nodules of variable size scattered throughout both [[lungs]].[[CT scan]] may be performed to detect [[metastasis]] of choriocarcinoma to [[lung]], [[brain]], and [[liver]].[[MRI]] may be performed to detect [[metastasis]] of choriocarcinoma to [[brain]] and [[spinal cord]]. | |||
== | == Historical Perspective == | ||
In 6th century, Aetius of Amida, a [[physician]] at Justinian's court came up with the term 'hydatid'. Next mention of 'mole' is from 1276 when Margaret, Countess of Henneberg, delivered approximately 300 babies on Good Friday (the Friday before Easter Sunday). In 1827, Marie Anne Victoire Boivin, a Parisian [[Midwifery|midwife]], proposed her findings of this condition in 'Nouvelles Recherches de la Mole Visiculaire' (News Searches of the Vesicular Mole). In 1840, William Wilton reported a case of invasive mole that was complicated by [[Uterine rupture|uterine]] [[perforation]] and fatal internal [[Bleeding|hemorrhage]]. In 1867, Richard von Volkmann, a German [[surgeon]], also described a [[lesion]] resembling an invasive mole. In 1877, Hans Chiari, an Austrian [[Pathology|pathologist]], reported three cases of choriocarcinoma. He recognized the [[Tumor|tumors]] as [[Epithelium|epithelial]]. In 1888, Max Sanger, a German [[Obstetrics|obstetrician]], proposed his [[theory]] that these [[Tumor|tumors]] were actually [[Sarcoma|sarcomas]]('deciduoma malignum'). In 1890, Pfeiffer, a student of Hans Chiari, re-examined Chiari's cases and added a fourth case. He named them all 'deciduoma malignum'. In 1891, Pestalozza from Italy, reported three cases of a [[malignant]][[Uterus|uterine]] [[tumor]] associated with [[pregnancy]]. He described these cases as 'sarcoma hemorrhagicum sen infectiosum'. | |||
==Classification== | ==Classification== | ||
Gestational trophoblastic neoplasia may be classified according to [[histology]] into four subtypes: invasive mole, choriocarcinoma, placental-site trophoblastic[[ tumor]], and epithelioid trophoblastic tumor. | Gestational trophoblastic neoplasia may be classified according to [[histology]] into four subtypes: invasive mole, choriocarcinoma, placental-site trophoblastic[[ tumor]], and epithelioid trophoblastic tumor. | ||
==Pathophysiology== | ==Pathophysiology== | ||
Gestational trophoblastic neoplasia | [[Pregnancy]] occurs when an [[Ovum|egg]], which is released from the [[ovary]] during [[ovulation]], is fertilized by a [[sperm]]. Human [[pregnancy]] takes approximately 40 weeks. Gestational trophoblastic neoplasia arises from the [[Trophoblast|trophoblastic]] tissue, which provides nutrients to the [[embryo]] and develops into a large part of the [[placenta]]. Invasive mole is basically a [[benign]] [[tumor]] which arises from the invasion of the [[myometrium]] of a [[hydatidiform mole]]. Choriocarcinoma is a [[malignant]] [[tumor]] of the [[Trophoblast|trophoblastic]] [[epithelium]]. Placental-site trophoblastic tumor (PSTT), a rare [[tumor]], arises from the [[implantation]] site of [[placenta]]. Epithelioid trophoblastic tumor (ETT) is basically a rare variant of placental-site trophoblastic tumor (PSTT) which arises from the [[malignant]] transformation of [[Chorion|chorionic]]-type intermediate [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]]. Invasive mole is usually [[Ploidy|diploid]] but can also be [[Aneuploidy|aneuploid]] in [[Karyotype|karyotype.]] Choriocarcinoma has an [[Aneuploidy|aneuploid]][[karyotype]] and majority of the cases have a [[Y chromosome]]. | ||
== Causes == | |||
[[Hydatidiform mole|Complete hydatidiform mole]] arises when an [[ovum]] without maternal [[Chromosome|chromosomes]] is [[Fertilization|fertilized]] by one [[sperm]] which duplicates its [[DNA]], resulting in a 46XX androgenetic [[karyotype]]. [[Hydatidiform mole|Partial hydatidiform moles]] are almost always [[Polyploidy|triploid]], resulting from the [[fertilization]] of a healthy [[ovum]] by two [[Sperm|sperms]]. Abnormal [[Trophoblast|trophoblastic]] population undergoing [[hyperplasia]] and [[anaplasia]] can give rise to choriocarcinoma. [[Gestation|Gestational]] type choriocarcinoma arises following a [[hydatidiform mole]], normal [[pregnancy]], or most commonly, abortion. Non-[[Gestation|gestational]] type choriocarcinoma arises from [[Pluripotency|pluripotent]] [[Germ cell|germ cells]]. [[Placenta|Placental]]-site [[Trophoblast|trophoblastic]] [[tumor]] (PSTT) arises from the [[Placenta|placental]] implantation site when the [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]] infiltrate the [[myometrium]]. [[Epithelioid]] [[Trophoblast|trophoblastic]] [[tumor]] (ETT) arises from the intermediate [[Trophoblast|trophoblastic]] [[Cell (biology)|cells]] of [[chorion]]. | |||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar [[symptoms]] and signs such as increase in [[uterine]] size, [[vaginal bleeding]] and [[amenorrhea]]. The differentials include [[molar pregnancy]] ([[Complete mole|complete]] and [[Molar pregnancy|partial moles]]), [[Ovarian tumor|ovarian tumors]], [[Spontaneous abortions|spontaneous abortion]], [[ectopic pregnancy]] and normal [[Pregnancy|term pregnancy]]. | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
The [[incidence]] of choriocarcinoma is approximately | The reported [[incidence]] of choriocarcinoma in the United States is 2 to 7 per 100,000 [[Pregnancy|pregnancies]]. The U.S. age-standardized (1960 World Population Standard) [[incidence]] rate of choriocarcinoma is approximately 0.18/100,000 women between the ages of 15 - 49 years. The [[prevalence]] of choriocarcinoma in the United States is 0.075 - 0.01 per 100, 000. The [[prevalence]] rates from Southeast Asia are 1.5 - 2.5 times higher. The 5-year overall [[mortality rate]], after the exclusion of [[Placenta|placental]] site [[Trophoblast|trophoblastic]] [[Tumor|tumors]] and [[epithelioid]] [[Trophoblast|trophoblastic]] [[Tumor|tumors]], is 2%. High-risk [[Patient|patients]] have a 5-year [[mortality rate]] of 12%. [[Patient|Patients]] with an [[International Federation of Gynecology and Obstetrics|International Federation of Gynecology and Obstetrics (FIGO)]] score of ≥13 have a 5-year [[mortality rate]] of 38.4%. The [[incidence]] of gestational trophoblastic neoplasia is higher in the extremes of [[Reproduction|reproductive]] ages. In Southasia, the [[incidence]] rates are double for Eurasians as compared to people of Chinese, Malaysian, or Indian origin. African Americans have a decreased [[incidence]] rate as compared to caucasians. The [[incidence]] is also higher in the Latin American population. Europe, North America, Australia, some areas of Latin America, and the Middle East have low [[incidence]] ratios. | ||
==Risk Factors== | ==Risk Factors== | ||
Common risk factors in the development of | Common [[Risk factor|risk factors]] in the development choriocarcinoma include extremes of parental [[Reproduction|reproductive]] age, history of [[gestational trophoblastic disease]], [[Reproduction|reproductive]] factors such as [[Parity (medicine)|parity]] and abortion, parental [[Blood type|blood group]], [[oral contraceptive]] use, [[Genetics|genetic]] factors, and environmental and lifestyle factors. | ||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
[[Patient|Patients]] with gestational trophoblastic neoplasia (GTN) initially present with abnormal [[Vagina|vaginal]] [[bleeding]]. The [[Vagina|vaginal]] [[bleeding]] can also be associated with elevation of [[Human chorionic gonadotropin|βhCG]]. In rare instances, [[Patient|patients]] can also initially present with [[Symptom|symptoms]] related to distant [[metastasis]] to different [[Organ (anatomy)|organs]]. [[Patient|Patients]] can experience [[nausea and vomiting]] similar to the course of normal [[pregnancy]]. If left untreated, [[Patient|patients]] with gestational trophoblastic neoplasia (GTN) may develop [[Metastasis|metastatic]] [[Lesion|lesions]] in different [[Organ (anatomy)|organs]] and can result in death. [[Complication (medicine)|Complications]] of gestational trophoblastic neoplasia (GTN) include disseminated [[Disease|disease,]] [[Exsanguination|hemorrhagic shock]], massive [[hemoptysis]], [[Acute abdomen]], [[Ovarian hyperstimulation syndrome|ovarian hyperstimulation]], [[Kidney|renal]] [[Bleeding|hemorrhage]], severe [[hyperthyroidism]], cardiothyreosis, and death. Poor prognostic factors include age > 35 years, interval since the last [[pregnancy]] of over 2 years, deep [[Myometrium|myometrial]] invasion, advanced stage, maximum [[Human chorionic gonadotropin|βhCG]] level > 1000 mIU/ml, extensive [[coagulative necrosis]], high [[Mitosis|mitotic]] rate, and presence of [[Cell (biology)|cells]] with clear [[cytoplasm]]. | |||
==Diagnosis== | ==Diagnosis== | ||
===Staging=== | ===Staging=== | ||
According to the Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) [[cancer staging]] system, there are 4 stages of choriocarcinoma. | According to the Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) [[cancer staging]] system, there are 4 stages of choriocarcinoma. | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
Symptoms of choriocarcinoma include [[vaginal bleeding]], passing of tissue resembling a “bunch of grapes” from the vagina, and abdominal distention. | [[Symptoms]] of choriocarcinoma include [[vaginal bleeding]], passing of [[Tissue (biology)|tissue]] resembling a “bunch of grapes” from the vagina, and [[abdominal distention]]. | ||
===Physical Examination=== | ===Physical Examination=== | ||
Common physical examination findings of choriocarcinoma include [[abdominal distention]], [[pelvic]]/adnexal mass, and blood in vaginal discharge. | Common physical examination findings of choriocarcinoma include [[abdominal distention|abdominal distension]], [[pelvic]]/adnexal mass, and [[blood]] in [[vaginal discharge]]. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Elevated serum [[human chorionic gonadotropin]] is diagnostic of choriocarcinoma. | Elevated serum [[human chorionic gonadotropin]] is diagnostic of choriocarcinoma. | ||
===Chest Xray=== | ===Chest Xray=== | ||
[[Chest radiography]] (CXR) may be helpful in the diagnosis of [[pulmonary]] [[ | [[Chest radiography]] (CXR) may be helpful in the diagnosis of [[pulmonary]] [[metastasis]] of choriocarcinoma. The characteristic findings of [[pulmonary]] [[metastasis]] are peripheral, rounded nodules of variable size scattered throughout both [[lungs]]. | ||
===CT=== | ===CT=== | ||
[[CT scan]] may be performed to detect [[ | [[CT scan]] may be performed to detect [[metastasis]] of choriocarcinoma to [[lung]], [[brain]], and [[liver]]. | ||
===MRI=== | ===MRI=== | ||
[[MRI]] may be performed to detect [[ | [[MRI]] may be performed to detect [[metastasis]] of choriocarcinoma to [[brain]] and [[spinal cord]]. | ||
===Ultrasound=== | ===Ultrasound=== | ||
[[Ultrasound]] may be performed to detect [[ | [[Ultrasound]] may be performed to detect [[metastasis]] of choriocarcinoma to the [[pelvis]] and [[abdomen]]. | ||
==Treatment== | ==Treatment== | ||
===Medical therapy=== | ===Medical therapy=== | ||
The mainstay of therapy for choriocarcinoma is [[chemotherapy]]. | The mainstay of therapy for choriocarcinoma is [[chemotherapy]]. | ||
===Surgery=== | ===Surgery=== | ||
[[Surgery]] is the mainstay of treatment for choriocarcinoma. | [[Surgery]] is the mainstay of treatment for choriocarcinoma. | ||
== Prevention == | |||
=== Primary prevention === | |||
There are no established measures for primary prevention of gestational trophoblastic neoplasia. | |||
=== Secondary prevention === | |||
Careful monitoring after the removal of [[Hydatidiform mole (patient information)|hydatidiform mole]] or termination of pregnancy can lead to early diagnosis of a choriocarcinoma, which improves outcome. | |||
==References== | ==References== | ||
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Latest revision as of 20:17, 19 March 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]
Overview
Gestational trophoblastic disease (GTD) includes several rare tumors that occur in the uterus and start in the cells that form the placenta during pregnancy. In 6th century, Aetius of Amida, a physician at Justinian's court came up with the term 'hydatid'. Next mention of 'mole' is from 1276 when Margaret, Countess of Henneberg, delivered approximately 300 babies on Good Friday (the Friday before Easter Sunday). In 1827, Marie Anne Victoire Boivin, a Parisian midwife, proposed her findings of this condition in 'Nouvelles Recherches de la Mole Visiculaire' (News Searches of the Vesicular Mole). In 1840, William Wilton reported a case of invasive mole that was complicated by uterine perforation and fatal internal hemorrhage. In 1867, Richard von Volkmann, a German surgeon, also described a lesion resembling an invasive mole. In 1877, Hans Chiari, an Austrian pathologist, reported three cases of choriocarcinoma. He recognized the tumors as epithelial. In 1888, Max Sanger, a German obstetrician, proposed his theory that these tumors were actually sarcomas ('deciduoma malignum'). In 1890, Pfeiffer, a student of Hans Chiari, re-examined Chiari's cases and added a fourth case. He named them all 'deciduoma malignum'. In 1891, Pestalozza from Italy, reported three cases of a malignantuterine tumor associated with pregnancy. He described these cases as 'sarcoma hemorrhagicum sen infectiosum'. Gestational trophoblastic neoplasia may be classified according to histology into four subtypes: invasive mole, choriocarcinoma, placental-site trophoblastictumor, and epithelioid trophoblastic tumor. Pregnancy occurs when an egg, which is released from the ovary during ovulation, is fertilized by a sperm. Human pregnancy takes approximately 40 weeks. Gestational trophoblastic neoplasia arises from the trophoblastic tissue, which provides nutrients to the embryo and develops into a large part of the placenta. Invasive mole is basically a benign tumor which arises from the invasion of the myometrium of a hydatidiform mole. Choriocarcinoma is a malignant tumor of the trophoblastic epithelium. Placental-site trophoblastic tumor (PSTT), a rare tumor, arises from the implantation site of placenta. Epithelioid trophoblastic tumor (ETT) is basically a rare variant of placental-site trophoblastic tumor (PSTT) which arises from the malignant transformation of chorionic-type intermediate trophoblastic cells. Invasive mole is usually diploid but can also be aneuploid in karyotype. Choriocarcinoma has an aneuploidkaryotype and majority of the cases have a Y chromosome. Complete hydatidiform mole arises when an ovum without maternal chromosomes is fertilized by one sperm which duplicates its DNA, resulting in a 46XX androgenetic karyotype. Partial hydatidiform moles are almost always triploid, resulting from the fertilization of a healthy ovum by two sperms. Abnormal trophoblastic population undergoing hyperplasia and anaplasia can give rise to choriocarcinoma. Gestational type choriocarcinoma arises following a hydatidiform mole, normal pregnancy, or most commonly, abortion. Non-gestational type choriocarcinoma arises from pluripotent germ cells. Placental-site trophoblastic tumor (PSTT) arises from the placental implantation site when the trophoblastic cells infiltrate the myometrium. Epithelioid trophoblastic tumor (ETT) arises from the intermediate trophoblastic cells of chorion.Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar symptoms and signs such as increase in uterine size, vaginal bleeding and amenorrhea. The differentials include molar pregnancy (complete and partial moles), ovarian tumors, spontaneous abortion, ectopic pregnancy and normal term pregnancy.The reported incidence of choriocarcinoma in the United States is 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is approximately 0.18/100,000 women between the ages of 15 - 49 years. The prevalence of choriocarcinoma in the United States is 0.075 - 0.01 per 100, 000. The prevalence rates from Southeast Asia are 1.5 - 2.5 times higher. The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, is 2%. High-risk patients have a 5-year mortality rate of 12%. Patients with an International Federation of Gynecology and Obstetrics (FIGO) score of ≥13 have a 5-year mortality rate of 38.4%. The incidence of gestational trophoblastic neoplasia is higher in the extremes of reproductive ages. In Southasia, the incidence rates are double for Eurasians as compared to people of Chinese, Malaysian, or Indian origin. African Americans have a decreased incidence rate as compared to caucasians. The incidence is also higher in the Latin American population. Europe, North America, Australia, some areas of Latin America, and the Middle East have low incidence ratios.Symptoms of choriocarcinoma include vaginal bleeding, passing of tissue resembling a “bunch of grapes” from the vagina, and abdominal distention. Elevated serum human chorionic gonadotropin suggests diagnostic of choriocarcinoma.Chest radiography (CXR) may be helpful in the diagnosis of pulmonary metastasis of choriocarcinoma. The characteristic findings of pulmonary metastasis are peripheral, rounded nodules of variable size scattered throughout both lungs.CT scan may be performed to detect metastasis of choriocarcinoma to lung, brain, and liver.MRI may be performed to detect metastasis of choriocarcinoma to brain and spinal cord.
Historical Perspective
In 6th century, Aetius of Amida, a physician at Justinian's court came up with the term 'hydatid'. Next mention of 'mole' is from 1276 when Margaret, Countess of Henneberg, delivered approximately 300 babies on Good Friday (the Friday before Easter Sunday). In 1827, Marie Anne Victoire Boivin, a Parisian midwife, proposed her findings of this condition in 'Nouvelles Recherches de la Mole Visiculaire' (News Searches of the Vesicular Mole). In 1840, William Wilton reported a case of invasive mole that was complicated by uterine perforation and fatal internal hemorrhage. In 1867, Richard von Volkmann, a German surgeon, also described a lesion resembling an invasive mole. In 1877, Hans Chiari, an Austrian pathologist, reported three cases of choriocarcinoma. He recognized the tumors as epithelial. In 1888, Max Sanger, a German obstetrician, proposed his theory that these tumors were actually sarcomas('deciduoma malignum'). In 1890, Pfeiffer, a student of Hans Chiari, re-examined Chiari's cases and added a fourth case. He named them all 'deciduoma malignum'. In 1891, Pestalozza from Italy, reported three cases of a malignantuterine tumor associated with pregnancy. He described these cases as 'sarcoma hemorrhagicum sen infectiosum'.
Classification
Gestational trophoblastic neoplasia may be classified according to histology into four subtypes: invasive mole, choriocarcinoma, placental-site trophoblastictumor, and epithelioid trophoblastic tumor.
Pathophysiology
Pregnancy occurs when an egg, which is released from the ovary during ovulation, is fertilized by a sperm. Human pregnancy takes approximately 40 weeks. Gestational trophoblastic neoplasia arises from the trophoblastic tissue, which provides nutrients to the embryo and develops into a large part of the placenta. Invasive mole is basically a benign tumor which arises from the invasion of the myometrium of a hydatidiform mole. Choriocarcinoma is a malignant tumor of the trophoblastic epithelium. Placental-site trophoblastic tumor (PSTT), a rare tumor, arises from the implantation site of placenta. Epithelioid trophoblastic tumor (ETT) is basically a rare variant of placental-site trophoblastic tumor (PSTT) which arises from the malignant transformation of chorionic-type intermediate trophoblastic cells. Invasive mole is usually diploid but can also be aneuploid in karyotype. Choriocarcinoma has an aneuploidkaryotype and majority of the cases have a Y chromosome.
Causes
Complete hydatidiform mole arises when an ovum without maternal chromosomes is fertilized by one sperm which duplicates its DNA, resulting in a 46XX androgenetic karyotype. Partial hydatidiform moles are almost always triploid, resulting from the fertilization of a healthy ovum by two sperms. Abnormal trophoblastic population undergoing hyperplasia and anaplasia can give rise to choriocarcinoma. Gestational type choriocarcinoma arises following a hydatidiform mole, normal pregnancy, or most commonly, abortion. Non-gestational type choriocarcinoma arises from pluripotent germ cells. Placental-site trophoblastic tumor (PSTT) arises from the placental implantation site when the trophoblastic cells infiltrate the myometrium. Epithelioid trophoblastic tumor (ETT) arises from the intermediate trophoblastic cells of chorion.
Differential Diagnosis
Gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental-site trophoblastic tumor [PSTT] and epitheloid trophoblastic tumor [ETT]) should be differentiated from other conditions presenting with similar symptoms and signs such as increase in uterine size, vaginal bleeding and amenorrhea. The differentials include molar pregnancy (complete and partial moles), ovarian tumors, spontaneous abortion, ectopic pregnancy and normal term pregnancy.
Epidemiology and Demographics
The reported incidence of choriocarcinoma in the United States is 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is approximately 0.18/100,000 women between the ages of 15 - 49 years. The prevalence of choriocarcinoma in the United States is 0.075 - 0.01 per 100, 000. The prevalence rates from Southeast Asia are 1.5 - 2.5 times higher. The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, is 2%. High-risk patients have a 5-year mortality rate of 12%. Patients with an International Federation of Gynecology and Obstetrics (FIGO) score of ≥13 have a 5-year mortality rate of 38.4%. The incidence of gestational trophoblastic neoplasia is higher in the extremes of reproductive ages. In Southasia, the incidence rates are double for Eurasians as compared to people of Chinese, Malaysian, or Indian origin. African Americans have a decreased incidence rate as compared to caucasians. The incidence is also higher in the Latin American population. Europe, North America, Australia, some areas of Latin America, and the Middle East have low incidence ratios.
Risk Factors
Common risk factors in the development choriocarcinoma include extremes of parental reproductive age, history of gestational trophoblastic disease, reproductive factors such as parity and abortion, parental blood group, oral contraceptive use, genetic factors, and environmental and lifestyle factors.
Natural History, Complications and Prognosis
Patients with gestational trophoblastic neoplasia (GTN) initially present with abnormal vaginal bleeding. The vaginal bleeding can also be associated with elevation of βhCG. In rare instances, patients can also initially present with symptoms related to distant metastasis to different organs. Patients can experience nausea and vomiting similar to the course of normal pregnancy. If left untreated, patients with gestational trophoblastic neoplasia (GTN) may develop metastatic lesions in different organs and can result in death. Complications of gestational trophoblastic neoplasia (GTN) include disseminated disease, hemorrhagic shock, massive hemoptysis, Acute abdomen, ovarian hyperstimulation, renal hemorrhage, severe hyperthyroidism, cardiothyreosis, and death. Poor prognostic factors include age > 35 years, interval since the last pregnancy of over 2 years, deep myometrial invasion, advanced stage, maximum βhCG level > 1000 mIU/ml, extensive coagulative necrosis, high mitotic rate, and presence of cells with clear cytoplasm.
Diagnosis
Staging
According to the Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) cancer staging system, there are 4 stages of choriocarcinoma.
History and Symptoms
Symptoms of choriocarcinoma include vaginal bleeding, passing of tissue resembling a “bunch of grapes” from the vagina, and abdominal distention.
Physical Examination
Common physical examination findings of choriocarcinoma include abdominal distension, pelvic/adnexal mass, and blood in vaginal discharge.
Laboratory Findings
Elevated serum human chorionic gonadotropin is diagnostic of choriocarcinoma.
Chest Xray
Chest radiography (CXR) may be helpful in the diagnosis of pulmonary metastasis of choriocarcinoma. The characteristic findings of pulmonary metastasis are peripheral, rounded nodules of variable size scattered throughout both lungs.
CT
CT scan may be performed to detect metastasis of choriocarcinoma to lung, brain, and liver.
MRI
MRI may be performed to detect metastasis of choriocarcinoma to brain and spinal cord.
Ultrasound
Ultrasound may be performed to detect metastasis of choriocarcinoma to the pelvis and abdomen.
Treatment
Medical therapy
The mainstay of therapy for choriocarcinoma is chemotherapy.
Surgery
Surgery is the mainstay of treatment for choriocarcinoma.
Prevention
Primary prevention
There are no established measures for primary prevention of gestational trophoblastic neoplasia.
Secondary prevention
Careful monitoring after the removal of hydatidiform mole or termination of pregnancy can lead to early diagnosis of a choriocarcinoma, which improves outcome.