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Gestational trophoblastic neoplasia


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]Syed Hassan A. Kazmi BSc, MD [3]Monalisa Dmello, M.B,B.S., M.D. [4]

Synonyms and Keywords: Chorioblastoma; Trophoblastic tumor; Chorioepithelioma; Gestational trophoblastic neoplasia; Gestational trophoblastic tumor; Placental site trophoblastic tumor; Epithelioid trophoblastic tumor; Exaggerated placenta site (EPS) tumor; Placental site nodule (PSN) tumor.

Overview

Overview

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.

References


Template:WikiDoc Sources

Historical Perspective

Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

Overview

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 malignant uterine tumor associated with pregnancy. He described these cases as ‘sarcoma hemorrhagicum sen infectiosum’.

Historical Perspective

Discovery

  • In 400 BC, Hippocrates is considered to be referring to gestational trophoblastic disease when he described ‘dropsy’ of the uterus.[1]
  • In 6th century, Aetius of Amida, a physician at Justinian’s court came up with the term ‘hydatid’.[2]
  • Next mention of ‘mole’ is from 1276 when Margaret, Countess of Henneberg, delivered approximately 300 babies on Good Friday (the Friday before Easter Sunday).[2]
  • 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).[2]
  • In 1840, William Wilton reported a case of invasive mole that was complicated by uterine perforation and fatal internal hemorrhage.[2]
  • In 1867, Richard von Volkmann, a German surgeon, also described a lesion resembling an invasive mole.[2]
  • In 1877, Hans Chiari, an Austrian pathologist, reported three cases of choriocarcinoma. He recognized the tumors as epithelial.[2]
  • In 1888, Max Sanger, a German obstetrician, proposed his theory that these tumors were actually sarcomas (‘deciduoma malignum’).[2]
  • In 1890, Pfeiffer, a student of Hans Chiari, re-examined Chiari’s cases and added a fourth case. He named them all ‘deciduoma malignum’.[2]
  • In 1891, Pestalozza from Italy, reported three cases of a malignant uterine tumor associated with pregnancy. He described these cases as ‘sarcoma hemorrhagicum sen infectiosum’.
  • In 1895, Felix Jacob Marchand, a German pathologist, reported two cases and he proposed that the tumors were epithelial. He traced their histogenesis to the coats of chorionic villi, hence the term ‘chorionepithelioma’.[2]
  • In 1903, John Teacher presented a detailed account of Marchand’s work along with two cases of his own and a literature review of 100 cases. He persuaded the Obstetrical Society of London that chorionepithelioma was derived from trophoblast.
  • In 1910, Ewing coined the term ‘syncytial endometritis’ to describe the exaggerated reaction of the placental site following hydatidiform mole.[2]

Landmark Events in the Development of Treatment Strategies

References

  1. ↑ Seckl MJ, Sebire NJ, Berkowitz RS (August 2010). “Gestational trophoblastic disease”. Lancet. 376 (9742): 717–29. doi:10.1016/S0140-6736(10)60280-2. PMID 20673583.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Ober WB (December 1986). “Trophoblastic disease: a retrospective view”. Hum. Reprod. 1 (8): 553–7. PMID 3029160.
  3. ↑ Yarris JP, Hunter AJ (May 2003). “Roy Hertz, M.D. (1909-2002): the cure of choriocarcinoma and its impact on the development of chemotherapy for cancer”. Gynecol. Oncol. 89 (2): 193–8. PMID 12765173.


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Classification

Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]

Overview

Gestational trophoblastic neoplasia may be classified according to histology into invasive mole, choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor.

Classification

Gestational trophoblastic neoplasia is classified as follows: [1]

References

  1. ↑ Cellular Classification of Gestational Trophoblastic Disease. National Cancer Institute. http://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq/#section/_5 Accessed on October 8, 2015

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Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

Overview

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 aneuploid karyotype and majority of the cases have a Y chromosome.

Pathophysiology

Physiology

The normal physiology of pregnancy can be understood as follows:

Placental Trophoblast and Pregnancy

For more information on fertilization, click here.
For more information on pregnancy, click here.

Pathogenesis

Pathogenesis of each sub-type of gestational trophoblastic neoplasia is explained as follows:

Invasive Mole

Choriocarcinoma

Placental-site Trophoblastic Tumor (PSTT)

Epithelioid Trophoblastic Tumor (ETT)

  • Epithelioid trophoblastic tumor (ETT) is basically a rare variant of placental-site trophoblastic tumor (PSTT).
  • It arises from the malignant transformation of chorionic-type intermediate trophoblastic cells.[27]
  • Epithelioid trophoblastic tumor (ETT) can clinically present as benign or malignant.[28]
  • Majority of the cases of epithelioid trophoblastic tumors (ETT) present years after full-term gestations.[27][29]

Genetics

Associated Conditions

Conditions associated with gestational trophoblastic neoplasia include:

Gross Pathology

Gross pathological findings of the sub-types of gestational trophoblastic neoplasia are as follows:

Invasive mole

Choriocarcinoma

Epithelioid Trophoblastic Tumor (ETT)

Placental-site Trophoblastic Tumor (PSTT)

Microscopic Pathology

On microscopic histopathological analysis, the characteristic features of each sub-type of gestational trophoblastic neoplasia are explained in the table below:[44][45][46]

Types of Gestational Trophoblastic Neoplasia Histopathological features

Invasive mole

Choriocarcinoma

Placental-site trophoblastic tumor

Epithelioid trophoblastic tumor

Courtesy Wikipedia

References

  1. ↑ CHANG MC (October 1951). “Fertilizing capacity of spermatozoa deposited into the fallopian tubes”. Nature. 168 (4277): 697–8. PMID 14882325.
  2. ↑ AUSTIN CR (November 1951). “Observations on the penetration of the sperm in the mammalian egg”. Aust J Sci Res B. 4 (4): 581–96. PMID 14895481.
  3. ↑ AUSTIN CR (August 1952). “The capacitation of the mammalian sperm”. Nature. 170 (4321): 326. PMID 12993150.
  4. ↑ Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.
  5. ↑ Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.
  6. ↑ Miklavcic JJ, Flaman P (May 2017). “Personhood status of the human zygote, embryo, fetus”. Linacre Q. 84 (2): 130–144. doi:10.1080/00243639.2017.1299896. PMC 5499222. PMID 28698706.
  7. ↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
  8. ↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
  9. ↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
  10. ↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
  11. ↑ Lurain, John R. (2010). “Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole”. American Journal of Obstetrics and Gynecology. 203 (6): 531–539. doi:10.1016/j.ajog.2010.06.073. ISSN 0002-9378.
  12. ↑ https://www.cancer.gov
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 Seckl MJ, Sebire NJ, Berkowitz RS (August 2010). “Gestational trophoblastic disease”. Lancet. 376 (9742): 717–29. doi:10.1016/S0140-6736(10)60280-2. PMID 20673583.
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 Brown J, Naumann RW, Seckl MJ, Schink J (January 2017). “15years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage”. Gynecol. Oncol. 144 (1): 200–207. doi:10.1016/j.ygyno.2016.08.330. PMID 27743739.
  15. ↑ https://www.cancer.gov
  16. ↑ 16.0 16.1 16.2 Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C (October 2013). “Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”. Ann. Oncol. 24 Suppl 6: vi39–50. doi:10.1093/annonc/mdt345. PMID 23999759.
  17. ↑ https://www.cancer.gov
  18. ↑ Bishop BN, Edemekong PF. PMID 30571055. Missing or empty |title= (help)
  19. ↑ Mao TL, Kurman RJ, Huang CC, Lin MC, Shih I (November 2007). “Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis”. Am. J. Surg. Pathol. 31 (11): 1726–32. doi:10.1097/PAS.0b013e318058a529. PMID 18059230. Vancouver style error: initials (help)
  20. ↑ Shih I (July 2007). “Gestational trophoblastic neoplasia–pathogenesis and potential therapeutic targets”. Lancet Oncol. 8 (7): 642–50. doi:10.1016/S1470-2045(07)70204-8. PMID 17613426. Vancouver style error: initials (help)
  21. ↑ https://www.cancer.gov
  22. ↑ https://www.cancer.gov
  23. ↑ 23.0 23.1 Feltmate CM, Genest DR, Goldstein DP, Berkowitz RS (May 2002). “Advances in the understanding of placental site trophoblastic tumor”. J Reprod Med. 47 (5): 337–41. PMID 12063871.
  24. ↑ https://www.cancer.gov
  25. ↑ https://www.cancer.gov
  26. ↑ 26.0 26.1 Schmid P, Nagai Y, Agarwal R, Hancock B, Savage PM, Sebire NJ, Lindsay I, Wells M, Fisher RA, Short D, Newlands ES, Wischnewsky MB, Seckl MJ (July 2009). “Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study”. Lancet. 374 (9683): 48–55. doi:10.1016/S0140-6736(09)60618-8. PMID 19552948.
  27. ↑ 27.0 27.1 27.2 27.3 Shih IM, Kurman RJ (November 1998). “Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma”. Am. J. Surg. Pathol. 22 (11): 1393–403. PMID 9808132.
  28. ↑ https://www.cancer.gov
  29. ↑ 29.0 29.1 Allison KH, Love JE, Garcia RL (December 2006). “Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast”. Arch. Pathol. Lab. Med. 130 (12): 1875–7. doi:10.1043/1543-2165(2006)130[1875:ETTROA]2.0.CO;2. PMID 17149967.
  30. ↑ http://www.cancer.gov
  31. ↑ http://www.cancer.gov
  32. ↑ 32.0 32.1 Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau GA, Slim R (March 2006). “Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans”. Nat. Genet. 38 (3): 300–2. doi:10.1038/ng1740. PMID 16462743.
  33. ↑ 33.0 33.1 Parry DA, Logan CV, Hayward BE, Shires M, Landolsi H, Diggle C, Carr I, Rittore C, Touitou I, Philibert L, Fisher RA, Fallahian M, Huntriss JD, Picton HM, Malik S, Taylor GR, Johnson CA, Bonthron DT, Sheridan EG (September 2011). “Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte”. Am. J. Hum. Genet. 89 (3): 451–8. doi:10.1016/j.ajhg.2011.08.002. PMC 3169823. PMID 21885028.
  34. ↑ 34.0 34.1 von Welser SF, Grube M, Ortmann O (December 2015). “Invasive mole in a perimenopausal woman: a case report and systematic review”. Arch. Gynecol. Obstet. 292 (6): 1193–9. doi:10.1007/s00404-015-3777-z. PMID 26050078.
  35. ↑ Simes BC, Mbanaso AA, Zapata CA, Okoroji CM (2018). “Hyperthyroidism in a complete molar pregnancy with a mature cystic ovarian teratoma”. Thyroid Res. 11: 12. doi:10.1186/s13044-018-0056-7. PMC 6086074. PMID 30116304.
  36. ↑ Lu D, Tang JJ, Zakashansky K, Berkowitz RS, Kalir T, Liu Y (September 2017). “Heterotopic Pregnancy Including Intrauterine Normal Gestation and Tubal Complete Hydatidiform Mole: A Case Report and Review of the Literature”. Int. J. Gynecol. Pathol. 36 (5): 428–432. doi:10.1097/PGP.0000000000000347. PMID 28800576.
  37. ↑ Ober, William B.; Edgcomb, John H.; Price, Edward B. (1971). “THE PATHOLOGY OF CHORIOCARCINOMA”. Annals of the New York Academy of Sciences. 172 (10 Physiology a): 299–426. doi:10.1111/j.1749-6632.1971.tb34943.x. ISSN 0077-8923.
  38. ↑ Smith, Harriet O.; Kohorn, Ernest; Cole, Laurence A. (2005). “Choriocarcinoma and Gestational Trophoblastic Disease”. Obstetrics and Gynecology Clinics of North America. 32 (4): 661–684. doi:10.1016/j.ogc.2005.08.001. ISSN 0889-8545.
  39. ↑ Fadare O, Parkash V, Carcangiu ML, Hui P (January 2006). “Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement”. Mod. Pathol. 19 (1): 75–82. doi:10.1038/modpathol.3800485. PMID 16258513.
  40. ↑ Meydanli, Mutlu M.; Kucukali, Turkan; Usubutun, Alp; Ataoglu, Omur; Kafkasli, Ayse (2002). “Epithelioid Trophoblastic Tumor of the Endocervix: A Case Report”. Gynecologic Oncology. 87 (2): 219–224. doi:10.1006/gyno.2002.6820. ISSN 0090-8258.
  41. ↑ Young RH, Scully RE (March 1984). “Placental-site trophoblastic tumor: current status”. Clin Obstet Gynecol. 27 (1): 248–58. PMID 6200262.
  42. ↑ Baergen, Rebecca N.; Rutgers, Joanne L.; Young, Robert H.; Osann, Kathryn; Scully, Robert E. (2006). “Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance”. Gynecologic Oncology. 100 (3): 511–520. doi:10.1016/j.ygyno.2005.08.058. ISSN 0090-8258.
  43. ↑ Baergen RN, Rutgers J, Young RH (October 2003). “Extrauterine lesions of intermediate trophoblast”. Int. J. Gynecol. Pathol. 22 (4): 362–7. doi:10.1097/01.pgp.0000092132.88121.d1. PMID 14501817.
  44. ↑ Cellular Classification of Gestational Trophoblastic Disease. National Cancer Institute. http://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq/#section/_5 Accessed on October 8, 2015
  45. ↑ Young RH, Scully RE (March 1984). “Placental-site trophoblastic tumor: current status”. Clin Obstet Gynecol. 27 (1): 248–58. PMID 6200262.
  46. ↑ Allison KH, Love JE, Garcia RL (December 2006). “Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast”. Arch. Pathol. Lab. Med. 130 (12): 1875–7. doi:10.1043/1543-2165(2006)130[1875:ETTROA]2.0.CO;2. PMID 17149967.

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Causes

Causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

Overview

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 laeve.

Causes

The causality of gestational trophoblastic neoplasia based on the sub-types is as follows:

Invasive mole

Choriocarcinoma

Placental-site Trophoblastic Tumor (PSTT)

Epithelioid Trophoblastic Tumor (ETT)

References

  1. ↑ El-Helw LM, Hancock BW (August 2007). “Treatment of metastatic gestational trophoblastic neoplasia”. Lancet Oncol. 8 (8): 715–24. doi:10.1016/S1470-2045(07)70239-5. PMID 17679081.
  2. ↑ Seckl MJ, Sebire NJ, Berkowitz RS (August 2010). “Gestational trophoblastic disease”. Lancet. 376 (9742): 717–29. doi:10.1016/S0140-6736(10)60280-2. PMID 20673583.
  3. ↑ Shih I (July 2007). “Gestational trophoblastic neoplasia–pathogenesis and potential therapeutic targets”. Lancet Oncol. 8 (7): 642–50. doi:10.1016/S1470-2045(07)70204-8. PMID 17613426. Vancouver style error: initials (help)
  4. ↑ Shen, Yuanming; Wan, Xiaoyun; Xie, Xing (2017). “A metastatic invasive mole arising from iatrogenic uterus perforation”. BMC Cancer. 17 (1). doi:10.1186/s12885-017-3904-2. ISSN 1471-2407.
  5. ↑ Lurain JR (December 2010). “Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole”. Am. J. Obstet. Gynecol. 203 (6): 531–9. doi:10.1016/j.ajog.2010.06.073. PMID 20728069.
  6. ↑ 6.0 6.1 Stockton L, Green E, Kaur B, De Winton E (2018). “Non-Gestational Choriocarcinoma with Widespread Metastases Presenting with Type 1 Respiratory Failure in a 39-Year-Old Female: Case Report and Review of the Literature”. Case Rep Oncol. 11 (1): 151–158. doi:10.1159/000486639. PMC 5903105. PMID 29681814.
  7. ↑ https://www.cancer.gov/types/gestational-trophoblastic
  8. ↑ Stănculescu RV, Bauşic V, Vlădescu TC, Vasilescu F, Brătilă E (2016). “Epithelioid trophoblastic tumor: a case report and literature review”. Rom J Morphol Embryol. 57 (4): 1365–1370. PMID 28174805.

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Differentiating Gestational trophoblastic neoplasia from other Diseases

Differentiating Gestational trophoblastic neoplasia from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

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.

Differentiating Choriocarcinoma From Other Diseases

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 the following:

Differential Diagnosis Clinical Features Karyotype Immunostaining Management
Presenting Complaints Potential for Neoplastic Conversion Beta Human Chorionic Gonadotropin (Beta-hCG) Baseline Levels History of Pregnancy Theca Leutin Cysts Metastatic Route Cytokeratin 18 HLA-G Human Chorionic Gonadotropin (hCG) Transformation-Related Protein 63 (P63) Human Placental Lactogen (hPL) Melanoma Cell Adhesion Molecule (Mel-CAM) Ki67
Complete Hydatidiform Mole[1][2][3]
  • High rate of progression (15-20%)
  • Extremely high levels
    • >100000 mIU/ml in half of the patients
  • Not related
  • Present
  • 46, XX or 46 XY (Paternal dispermy)
  • Negative
  • Negative
  • Extremely elevated
  • Absent
  • Absent
  • Absent
  • Absent
  • Dilation and curettage (suction)
Partial Hydatidiform Mole[4][5][6]
  • < 5 % progression rate
  • Highly elevated
    • >100000 mIU/ml in one in ten patients
  • Not related
  • Absent
  • 69,XXY or XYY
  • Negative
  • Negative
  • Highly elevated
  • Absent
  • Absent
  • Absent
  • Absent
  • Dilation and curettage (suction)
Invasive Molar Pregnancy
  • High
  • May be present
  • Hematogenous
  • 69,XXY or XYY
  • Positive
  • Positive
  • Highly elevated
  • Absent
  • Absent
  • Absent
  • Absent
Choriocarcinoma[7][8][9]
  • High
  • Present
  • Hematogenous
  • Positive
  • Positive
  • Highly elevated
  • Positive
Placental-site Trophoblastic tumor (PSTT) and Epitheloid Trophoblastic Tumor (ETT)[10][11][12][13]
  • Neoplastic
  • Moderatley elevated
    • <1000 mIU/ml in majority of patients
  • Absent
  • 46,XX or XY
  • Positive
  • Positive
  • Negative (Positive in ETT)
  • Positive (Negative in ETT)
  • Positive (Negative in ETT)
  • Positive ( >1% in PSTT and >10% in ETT)
  • Hysterectomy
Ovarian Tumors[14][15][16][17][18][19][20][21][22]
  • Overall incidence in pregnancy is 2.4-5.7% (1/300 to 1/556 pregnancies)
  • Incidence of malignancy is 1/15,000 to 1/32,000 pregnancies
  • Germ cell and epithelial tumors are most common
  • Absent
  • Direct extension or seeding
  • Negative (Epithelial tumors may be positive for cytokeratin AE1/AE3)
  • Positive
  • Positive (especially in epithelial cancers)
  • Positive
  • Positive
  • Positive
  • Surgical debulking
  • Intravenous/intraperitoneal chemotherapy
Spontaneous Abortion[23][24]
  • Not applicable
  • Decline in levels within 24 hours
    • Absent
    • Not applicable
    • Negative
    • Negative
    • Progressive decline
    • Negative
    • Negative
    • Negative
    • Negative
    • Uterine evacuation if patient has sepsis, hemorrhage and/or intractable pain
    • Medical management using prostaglandin analogs
    • Expectant management if no complications
    Ectopic Pregnancy[25][26]
    • Not applicable
    • Failure of hCG doubling (especially during the first 8 weeks)
    • Absent
    • Not applicable
    • Negative
    • Negative
    • A rising β-hCG concentration that fails to reach 50% or plateaus
    • Negative
    • Negative
    • Negative
    • Negative
    • Expectant management (Failure of transvaginal ultrasonography to show the location of the gestational sac and the serum levels of β-hCG and progesterone are low and declining)
    • Surgical laproscopy
    Normal Term Pregnancy
    • Not applicable
    • Elevated (>25 mIU/mL)
    • Progressive elevation and doubling of levels every 2 days especially during first 8 weeks
    • Not applicable
    • Absent
    • Not applicable
    • Negative
    • Negative
    • Progressive elevation and doubling of levels every 2 days especially during first 8 weeks
    • Negative
    • Negative
    • Negative
    • Negative
    • Expectant delivery
    • C-section (elective or in cases of breach presentation)

    References

    1. ↑ Candelier JJ (March 2016). “The hydatidiform mole”. Cell Adh Migr. 10 (1–2): 226–35. doi:10.1080/19336918.2015.1093275. PMC 4853053. PMID 26421650.
    2. ↑ Cavaliere A, Ermito S, Dinatale A, Pedata R (January 2009). “Management of molar pregnancy”. J Prenat Med. 3 (1): 15–7. PMC 3279094. PMID 22439034.
    3. ↑ Sun SY, Melamed A, Joseph NT, Gockley AA, Goldstein DP, Bernstein MR, Horowitz NS, Berkowitz RS (February 2016). “Clinical Presentation of Complete Hydatidiform Mole and Partial Hydatidiform Mole at a Regional Trophoblastic Disease Center in the United States Over the Past 2 Decades”. Int. J. Gynecol. Cancer. 26 (2): 367–70. doi:10.1097/IGC.0000000000000608.
    4. ↑ Watson EJ, Hernandez E, Miyazawa K (September 1987). “Partial hydatidiform moles: a review”. 42 (9): 540–4.
    5. ↑ Goldstein DP, Berkowitz RS (March 1994). “Current management of complete and partial molar pregnancy”. J Reprod Med. 39 (3): 139–46. PMID 8035368.
    6. ↑ Szulman AE, Surti U (May 1982). “The clinicopathologic profile of the partial hydatidiform mole”. Obstet Gynecol. 59 (5): 597–602. PMID 7070731.
    7. ↑ Smith HO, Kohorn E, Cole LA (December 2005). “Choriocarcinoma and gestational trophoblastic disease”. Obstet. Gynecol. Clin. North Am. 32 (4): 661–84. doi:10.1016/j.ogc.2005.08.001. PMID 16310678.
    8. ↑ Baergen RN (November 1997). “Gestational choriocarcinoma”. Gen Diagn Pathol. 143 (2–3): 127–41. PMID 9443570.
    9. ↑ Duffy L, Zhang L, Sheath K, Love DR, George AM (December 2015). “The Diagnosis of Choriocarcinoma in Molar Pregnancies: A Revised Approach in Clinical Testing”. J Clin Med Res. 7 (12): 961–6. doi:10.14740/jocmr2236w. PMC 4625817. PMID 26566410.
    10. ↑ Horowitz NS, Goldstein DP, Berkowitz RS (January 2017). “Placental site trophoblastic tumors and epithelioid trophoblastic tumors: Biology, natural history, and treatment modalities”. Gynecol. Oncol. 144 (1): 208–214. doi:10.1016/j.ygyno.2016.10.024. PMID 27789086.
    11. ↑ Kim SJ (December 2003). “Placental site trophoblastic tumour”. Best Pract Res Clin Obstet Gynaecol. 17 (6): 969–84. PMID 14614893.
    12. ↑ Zhao J, Lv WG, Feng FZ, Wan XR, Liu JH, Yi XF, Qu PP, Xue FX, Wu YM, Zhao X, Ren T, Yang JJ, Xie X, Xiang Y (July 2016). “Placental site trophoblastic tumor: A review of 108 cases and their implications for prognosis and treatment”. Gynecol. Oncol. 142 (1): 102–108. doi:10.1016/j.ygyno.2016.05.006. PMID 27168005.
    13. ↑ Shih IM, Kurman RJ (January 1998). “Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies”. Hum. Pathol. 29 (1): 27–33. PMID 9445130.
    14. ↑ Farahmand SM, Marchetti DL, Asirwatham JE, Dewey MR (May 1991). “Ovarian endodermal sinus tumor associated with pregnancy: review of the literature”. Gynecol. Oncol. 41 (2): 156–60. PMID 2050306.
    15. ↑ Hopkins MP, Duchon MA (November 1986). “Adnexal surgery in pregnancy”. J Reprod Med. 31 (11): 1035–7. PMID 3806533.
    16. ↑ Lavery JP, Koontz WL, Layman L, Shaw L, Gumpel U (October 1986). “Sonographic evaluation of the adnexa during early pregnancy”. Surg Gynecol Obstet. 163 (4): 319–23. PMID 3532382.
    17. ↑ Dgani R, Shoham Z, Atar E, Zosmer A, Lancet M (June 1989). “Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984”. Gynecol. Oncol. 33 (3): 326–31. PMID 2722058.
    18. ↑ Lengyel E (September 2010). “Ovarian cancer development and metastasis”. Am. J. Pathol. 177 (3): 1053–64. doi:10.2353/ajpath.2010.100105. PMC 2928939. PMID 20651229.
    19. ↑ Goel A, Rao NM, Santhi V, Byna SS, Grandhi B, Conjeevaram J (2018). “Immunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin”. Iran J Pathol. 13 (1): 23–29. PMC 5929385. PMID 29731792.
    20. ↑ Rebmann V, Regel J, Stolke D, Grosse-Wilde H (October 2003). “Secretion of sHLA-G molecules in malignancies”. Semin. Cancer Biol. 13 (5): 371–7. PMID 14708717.
    21. ↑ Zhou P, Xiong T, Chen J, Li F, Qi T, Yuan J (February 2019). “Clinical significance of melanoma cell adhesion molecule CD146 and VEGFA expression in epithelial ovarian cancer”. Oncol Lett. 17 (2): 2418–2424. doi:10.3892/ol.2018.9840. PMC 6341705. PMID 30675307.
    22. ↑ Mita S, Nakai A, Maeda S, Takeshita T (December 2004). “Prognostic significance of Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in ovarian cancer”. J Nippon Med Sch. 71 (6): 384–91. PMID 15673959.
    23. ↑ Barnhart K, Sammel MD, Chung K, Zhou L, Hummel AC, Guo W (November 2004). “Decline of serum human chorionic gonadotropin and spontaneous complete abortion: defining the normal curve”. Obstet Gynecol. 104 (5 Pt 1): 975–81. doi:10.1097/01.AOG.0000142712.80407.fd. PMID 15516387.
    24. ↑ Griebel CP, Halvorsen J, Golemon TB, Day AA (October 2005). “Management of spontaneous abortion”. Am Fam Physician. 72 (7): 1243–50. PMID 16225027.
    25. ↑ Murray H, Baakdah H, Bardell T, Tulandi T (October 2005). “Diagnosis and treatment of ectopic pregnancy”. CMAJ. 173 (8): 905–12. doi:10.1503/cmaj.050222. PMC 1247706. PMID 16217116.
    26. ↑ Murphy AA, Nager CW, Wujek JJ, Kettel LM, Torp VA, Chin HG (June 1992). “Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial”. Fertil. Steril. 57 (6): 1180–5. PMID 1534771.
    Epidemiology and Demographics

    Epidemiology and Demographics

    Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

    Overveiw

    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.

    Epidemiology and Demographics

    Incidence

    • The reported incidence of choriocarcinoma in the United States is 2 – 7 cases per 100,000 individuals pregnancies.[1]
    • The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is approximately 0.18 cases per 100,000 individual women between the ages of 15 – 49 years.[2]
    • The incidence in Europe ranges from 2 – 3 cases per 100,000 individuals.[3][4][5]
    • The incidence in Canada and Greenland is reported to be approximately 3 cases per 100,000 individuals.[6][7][8]
    • The reported incidence in Australia is 7 cases per 100,000 individuals.[9]
    • The incidence in Latin America is reported to be 2 cases per 100,000 individuals.[10][11][12]
    • The incidence in Saudi Arabia is reported to be 16 cases per 100,000 individuals.[13]
    • The incidence in Asia ranges from 5 – 202 cases per 100,000 individuals.[14][15][16][17][18]
    • The incidence in Nigeria is 99 cases per 100,000 individuals.[19][20]

    Prevalence

    • The prevalence of choriocarcinoma in the United States is 0.075 – 0.01 cases per 100,000 individuals.[21][22]
    • The prevalence rates from Southeast Asia are 1.5 – 2.5 times higher.[23][24]

    Mortality Rate

    Age

    Race

    • In Southasia, the incidence rates are double for Eurasians as compared to people of Chinese, Malaysian, or Indian origin.[26]
    • African Americans have a decreased incidence rate as compared to caucasians.[26]
    • The incidence is also higher in the Latin American population.[26]
    • Mexicans and Filipinos have elevated rates in comparison to Japanese and Chinese.[26]

    Region

    • Europe, North America, Australia, some areas of Latin America, and the Middle East have low incidence ratios.[27][28][5][15]
    • Studies from China, India, Indonesia, and Thailand show high incidence ratios.[29][18]

    References

    1. ↑ General Information About Gestational Trophoblastic Disease National Cancer Institute. http://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq/#section/_1. Accessed on October7, 2015
    2. ↑ Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C (November 2003). “Epidemiology and aetiology of gestational trophoblastic diseases”. Lancet Oncol. 4 (11): 670–8. PMID 14602247.
    3. ↑ Olsen, Jørgen H.; Mellemkjaer, Lene; Gridley, Gloria; Brinton, Louise; Johansen, Christoffer; Kjaer, Susanne Krüger (1999). “Molar pregnancy and risk for cancer in women and their male partners”. American Journal of Obstetrics and Gynecology. 181 (3): 630–634. doi:10.1016/S0002-9378(99)70504-1. ISSN 0002-9378.
    4. ↑ Flam F, Lundström-Lindstedt V, Rutqvist LE (March 1992). “Incidence of gestational trophoblastic disease in Stockholm County, 1975-1988”. Eur. J. Epidemiol. 8 (2): 173–7. PMID 1322822.
    5. ↑ 5.0 5.1 Ringertz N (1970). “Hydatidiform mole, invasive mole and choriocarcinoma in Sweden 1958-1965”. Acta Obstet Gynecol Scand. 49 (2): 195–203. PMID 5519491.
    6. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    7. ↑ Nielsen NH, Hansen JP (October 1979). “Trophoblastic tumors in Greenland”. J. Cancer Res. Clin. Oncol. 95 (2): 177–86. PMID 230189.
    8. ↑ Yen, Stella; MacMahon, Brian (1968). “Epidemiologic features of trophoblastic disease”. American Journal of Obstetrics and Gynecology. 101 (1): 126–132. doi:10.1016/0002-9378(68)90497-3. ISSN 0002-9378.
    9. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    10. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    11. ↑ Sengupta BS, Persaud V, Wynter HH (February 1977). “Choriocarcinoma in Jamaica”. Int Surg. 62 (2): 84–7. PMID 844972.
    12. ↑ Rolon PA, Hochsztajn de Lopez B (August 1979). “Malignant trophoblastic disease in paraguay”. J Reprod Med. 23 (2): 94–6. PMID 226699.
    13. ↑ Chattopadhyay SK, Sengupta BS, al-Ghreimil M, Edrees YB, Lambourne A (November 1988). “Epidemiologic study of gestational trophoblastic diseases in Saudi Arabia”. Surg Gynecol Obstet. 167 (5): 393–8. PMID 2845590.
    14. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    15. ↑ 15.0 15.1 Shanmugaratnam, K.; Muir, C. S.; Tow, S. H.; Cheng, W. C.; Christine, B.; Pedersen, E. (1971). “Rates per 100,000 births and incidence of choriocarcinoma and malignant mole in Singapore Chinese and Malays. Comparison with connecticut, Norway and Sweden”. International Journal of Cancer. 8 (1): 165–175. doi:10.1002/ijc.2910080120. ISSN 0020-7136.
    16. ↑ Nakano R, Sasaki K, Yamoto M, Hata H (1980). “Trophoblastic disease: analysis of 342 patients”. Gynecol. Obstet. Invest. 11 (4): 237–42. doi:10.1159/000299843. PMID 6256264.
    17. ↑ Baltazar JC (1976). “Epidemiological features of choriocarcinoma”. Bull. World Health Organ. 54 (5): 523–32. PMC 2366480. PMID 1088402.
    18. ↑ 18.0 18.1 Srivannaboon S, Vatananusara C, Boonyanit S (November 1974). “The incidence of trophoblastic disease in Siriraj Hospital”. J Med Assoc Thai. 57 (11): 537–42. PMID 4375696.
    19. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    20. ↑ Agboola A, Abudu OO (1984). “Epidemiology of trophoblast disease in Africa–Lagos”. Adv. Exp. Med. Biol. 176: 187–95. PMID 6093462.
    21. ↑ Buckley JD (March 1984). “The epidemiology of molar pregnancy and choriocarcinoma”. Clin Obstet Gynecol. 27 (1): 153–9. PMID 6705308.
    22. ↑ Burton JL, Lidbury EA, Gillespie AM, Tidy JA, Smith O, Lawry J, Hancock BW, Wells M (May 2001). “Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy”. Histopathology. 38 (5): 409–17. PMID 11422477.
    23. ↑ Cortes R. Enfenpraded trophoblastic gestational. In obstetrician Clinica. Second edition. Edited by IZigheelboim, D Guariglia. Caracas, Editorial Disinlimed. 2005:374–379.
    24. ↑ Kite NH, Lipscomb GH, Merrill K. Molar corneal ectopic pregnancy. Obstet Gynecol. 2002;99:689–692.
    25. ↑ 25.0 25.1 25.2 Bolze PA, Riedl C, Massardier J, Lotz JP, You B, Schott AM, Hajri T, Golfier F (March 2016). “Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13”. Am. J. Obstet. Gynecol. 214 (3): 390.e1–8. doi:10.1016/j.ajog.2015.09.083. PMID 26433171.
    26. ↑ 26.0 26.1 26.2 26.3 Tasha I, Kroi E, Karameta A, Shahinaj R, Manoku N (April 2010). “Prevalence of gestational trophoblastic disease in ectopic pregnancy”. J Prenat Med. 4 (2): 26–9. PMC 3279171. PMID 22439057.
    27. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.
    28. ↑ Smith, Harriet O.; Hilgers, Robert D.; Bedrick, Edward J.; Qualls, Clifford R.; Wiggins, Charles L.; Rayburn, William F.; Waxman, Alan G.; Stephens, Nicole D.; Cole, Laurence W.; Swanson, Marian; Key, Charles R. (2003). “Ethnic differences at risk for gestational trophoblastic disease in New Mexico: A 25-year population-based study”. American Journal of Obstetrics and Gynecology. 188 (2): 357–366. doi:10.1067/mob.2003.39. ISSN 0002-9378.
    29. ↑ LastName, FirstName (1983). Gestational trophoblastic diseases. Geneva: World Health Organization. ISBN 9241206926.

    Template:WH Template:WS

    Risk Factors

    Risk Factors

    Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

    Overview

    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.

    Risk factors

    Parental Age

    Maternal

    • The risk of choriocarcinoma increases progressively in women older than 25 years (relative risk 1·4).[1]
    • The risk increases more rapidly in women older than 39 years (relative risk 10·8).[1]
    • The risk is higher for women younger than 20 compared with women aged 20 – 24 years (relative risk 1·5).[1]

    Paternal

    History of Gestational Trophoblastic Disease

    Reproductive Factors

    • The risk of choriocarcinoma also increases with the history of abortion. Relative risk for 1 and 2 abortions is 1.2 (95% CI: 0·5–2·9) and 0.8 (95% CI: 0·3 – 2·5) respectively.[7]
    • A study on choriocarcinoma from Vietnam has shown a relative risk of 0·3 for a history of induced abortions.[7]

    Parental Blood Group

    Oral Contraceptives

    Genetic Factors

    Mutation in the following genes has been associated with recurrent hydatidiform mole:

    Environmental and Lifestyle Factors

    References

    1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Buckley JD (March 1984). “The epidemiology of molar pregnancy and choriocarcinoma”. Clin Obstet Gynecol. 27 (1): 153–9. PMID 6705308.
    2. ↑ La Vecchia C, Parazzini F, Decarli A, Franceschi S, Fasoli M, Favalli G, Negri E, Pampallona S (September 1984). “Age of parents and risk of gestational trophoblastic disease”. J. Natl. Cancer Inst. 73 (3): 639–42. PMID 6088880.
    3. ↑ Parazzini, F.; Vecchia, C. La; Pampallona, S. (1986). “Parental age and risk of complete and partial hydatidiform mole”. BJOG: An International Journal of Obstetrics and Gynaecology. 93 (4): 582–585. doi:10.1111/j.1471-0528.1986.tb07957.x. ISSN 1470-0328.
    4. ↑ 4.0 4.1 Brinton, Louise A.; Wu, Bao-Zhen; Wang, Wen; Ershow, Abby G.; Song, Hong-Zhao; Li, Jun-Yao; Bracken, Michael B.; Blot, William J. (1989). “Gestational trophoblastic disease: A case-control study from the People’s Republic of China”. American Journal of Obstetrics and Gynecology. 161 (1): 121–127. doi:10.1016/0002-9378(89)90248-2. ISSN 0002-9378.
    5. ↑ 5.0 5.1 Parazzini, Fabio; LaVecchia, Carlo; Pampallona, Sandro; Franceschi, Silvia (1985). “Reproductive patterns and the risk of gestational trophoblastic disease”. American Journal of Obstetrics and Gynecology. 152 (7): 866–870. doi:10.1016/S0002-9378(85)80079-X. ISSN 0002-9378.
    6. ↑ 6.0 6.1 6.2 La Vecchia C, Franceschi S, Parazzini F, Fasoli M, Decarli A, Gallus G, Tognoni G (March 1985). “Risk factors for gestational trophoblastic disease in Italy”. Am. J. Epidemiol. 121 (3): 457–64. PMID 2990199.
    7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Ha MC, Cordier S, Bard D, Le TB, Hoang AH, Hoang TQ, Le CD, Abenhaim L, Nguyen TN (1996). “Agent orange and the risk of gestational trophoblastic disease in Vietnam”. Arch. Environ. Health. 51 (5): 368–74. doi:10.1080/00039896.1996.9934424. PMID 8896386.
    8. ↑ Talati NJ (October 1998). “The pattern of benign gestational trophoblastic disease in Karachi”. J Pak Med Assoc. 48 (10): 296–300. PMID 10087749.
    9. ↑ Messerli, Marti L.; Lilienfeld, Abraham M.; Parmley, Tim; Woodruff, J. Donald; Rosenshein, Neil B. (1985). “Risk factors for gestational trophoblastic neoplasia”. American Journal of Obstetrics and Gynecology. 153 (3): 294–300. doi:10.1016/S0002-9378(85)80115-0. ISSN 0002-9378.
    10. ↑ Bagshawe, K.D.; Rawlins, G.; Pike, M.C.; Lawler, SylviaD. (1971). “ABO BLOOD-GROUPS IN TROPHOBLASTIC NEOPLASIA”. The Lancet. 297 (7699): 553–557. doi:10.1016/S0140-6736(71)91159-7. ISSN 0140-6736.
    11. ↑ 11.0 11.1 Baltazar JC (1976). “Epidemiological features of choriocarcinoma”. Bull. World Health Organ. 54 (5): 523–32. PMC 2366480. PMID 1088402.
    12. ↑ Buckley JD, Henderson BE, Morrow CP, Hammond CB, Kohorn EI, Austin DF (February 1988). “Case-control study of gestational choriocarcinoma”. Cancer Res. 48 (4): 1004–10. PMID 3338071.
    13. ↑ Palmer, J. R.; Driscoll, S. G.; Rosenberg, L.; Berkowitz, R. S.; Lurain, J. R.; Soper, J.; Twiggs, L. B.; Gershenson, D. M.; Kohorn, E. I.; Berman, M.; Shapiro, S.; Rao, R. S. (1999). “Oral Contraceptive Use and Risk of Gestational Trophoblastic Tumors”. JNCI Journal of the National Cancer Institute. 91 (7): 635–640. doi:10.1093/jnci/91.7.635. ISSN 0027-8874.
    14. ↑ 14.0 14.1 Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau GA, Slim R (March 2006). “Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans”. Nat. Genet. 38 (3): 300–2. doi:10.1038/ng1740. PMID 16462743.
    15. ↑ 15.0 15.1 Parry DA, Logan CV, Hayward BE, Shires M, Landolsi H, Diggle C, Carr I, Rittore C, Touitou I, Philibert L, Fisher RA, Fallahian M, Huntriss JD, Picton HM, Malik S, Taylor GR, Johnson CA, Bonthron DT, Sheridan EG (September 2011). “Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte”. Am. J. Hum. Genet. 89 (3): 451–8. doi:10.1016/j.ajhg.2011.08.002. PMC 3169823. PMID 21885028.
    Screening

    Screening

    Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

    Overview

    There is insufficient evidence to recommend routine screening for gestational trophoblastic neoplasia.

    Screening

    There is insufficient evidence to recommend routine screening for gestational trophoblastic neoplasia.

    References

    Template:WH Template:WS

    Natural History, Complications and Prognosis

    Natural History, Complications and Prognosis

    Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]

    Overview

    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.

    Natural History, Complications, and Prognosis

    Natural History

    Complications

    Prognosis

    Poor prognosis of gestational trophoblastic neoplasia (GTN) can be determined by the following factors:[12]

    References

    1. ↑ Killick S, Cook J, Gillett S, Ellis L, Tidy J, Hancock BW (2012). “Initial presenting features in gestational trophoblastic neoplasia: does a decade make a difference?”. J Reprod Med. 57 (7–8): 279–82. PMID 22838240.
    2. ↑ Meydanli MM, Kucukali T, Usubutun A, Ataoglu O, Kafkasli A (November 2002). “Epithelioid trophoblastic tumor of the endocervix: a case report”. Gynecol. Oncol. 87 (2): 219–24. PMID 12477457.
    3. ↑ 3.0 3.1 Zhang W, Liu B, Wu J, Sun B (April 2017). “Hemoptysis as primary manifestation in three women with choriocarcinoma with pulmonary metastasis: a case series”. J Med Case Rep. 11 (1): 110. doi:10.1186/s13256-017-1256-9. PMID 28411623.
    4. ↑ 4.0 4.1 Bishop BN, Edemekong PF. PMID 30571055. Missing or empty |title= (help)
    5. ↑ Piura E, Piura B (2014). “Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature”. Eur. J. Gynaecol. Oncol. 35 (4): 359–67. PMID 25118474.
    6. ↑ 6.0 6.1 6.2 Chauhan M, Behera C, Madireddi S, Mandal S, Khanna SK (July 2018). “Sudden death due to an invasive mole in a young primigravida: Precipitous presentation masquerading the natural manner”. Med Sci Law. 58 (3): 189–193. doi:10.1177/0025802418786120. PMID 29969941.
    7. ↑ Yadav RS, Shrestha S, Sharma S, Singh M, Bista KD, Ojha N (January 2018). “Partial Invasive Mole with Bilateral Torsion of Theca Lutein Cysts”. J Nepal Health Res Counc. 15 (3): 298–300. PMID 29353908.
    8. ↑ Alhalabi K, Lampl BS, Behr G (July 2016). “Ovarian hyperstimulation syndrome as a complication of molar pregnancy”. Cleve Clin J Med. 83 (7): 504–6. doi:10.3949/ccjm.83a.15036. PMID 27399862.
    9. ↑ Xiao S, Mu Q, Wan Y, Xue M (2016). “Spontaneous renal hemorrhage caused by invasive mole: a case report”. Eur. J. Gynaecol. Oncol. 37 (3): 417–9. PMID 27352577.
    10. ↑ 10.0 10.1 Marchand L, Chabert P, Chaudesaygues E, Grasse M, Bretones S, Graeppi-Dulac J, Aupetit JF (2016). “An unusual cause of cardiothyreosis”. Gynecol. Endocrinol. 32 (2): 107–9. doi:10.3109/09513590.2015.1111328. PMID 26559442.
    11. ↑ Simes BC, Mbanaso AA, Zapata CA, Okoroji CM (2018). “Hyperthyroidism in a complete molar pregnancy with a mature cystic ovarian teratoma”. Thyroid Res. 11: 12. doi:10.1186/s13044-018-0056-7. PMC 6086074. PMID 30116304.
    12. ↑ Rebecca N. Baergen, Joanne L. Rutgers, Robert H. Young, Kathryn Osann & Robert E. Scully (2006). “Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance”. Gynecologic oncology. 100 (3): 511–520. doi:10.1016/j.ygyno.2005.08.058. PMID 16246400. Unknown parameter |month= ignored (help)

    Template:WH Template:WS

    Diagnosis

    Diagnosis

    History and Symptoms | Physical Examination | Laboratory Findings | Chest X Ray | CT | MRI | Ultrasound | Other Imaging Findings | Other Diagnostic Studies

    Treatment

    Treatment

    Staging | Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

    Case Studies

    Case Studies

    Case #1

    Related Chapters

    Gestational trophoblastic disease


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