Gestational trophoblastic neoplasia pathophysiology

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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]Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

Gestational trophoblastic neoplasia arises from the trophoblastic tissue, which provides nutrients to the embryo and develops into a large part of the placenta. On gross pathology, gestational trophoblastic neoplasia is characterised by a dark, shaggy, focally hemorrhagic & friable/necrotic-appearing mass with invasive borders. The pathophysiology of gestational trophoblastic neoplasia depends on the histological subtype.^[1]^[2]^[3]

Pathophysiology

Physiology

The normal physiology of pregnancy can be understood as follows:

Pregnancy occurs when an egg, which is released from the ovary during ovulation, is fertilized by a sperm.
After ejaculation, the released sperm must spend some time in the female reproductive tract and undergo capacitation, which is basically the acquisition of fertilization capability.^[4]^[5]^[6]
The sperm then penetrates the egg after the acrosomal reaction and initiates the process of fertilization in the fallopian tube.^[7]
The sperm breaks through the oocyte's plasma membrane and releases its haploid nucleus into the oocyte.^[8]
Cortical reaction (changes in the oocyte membrane) prevents any further penetration by another sperm.
Unification of the two haploid nuclei (one each from the sperm and egg) marks the completion of fertilization, resulting in the formation of a diploid zygote.
The zygote undergoes multiple divisions called cleavage before its migration to the uterus.^[9]
Human pregnancy takes approximately 40 weeks.

Placental Trophoblast and Pregnancy

Trophoblast (outer layer of the blasotcyst) is composed of cytotrophoblast, syncytiotrophoblast, and intermediate trophoblast.^[10]
Syncytiotrophoblast invades the endometrial stroma and produces human chorionic gonadotropin (hCG).^[11]
Cytotrophoblast supplies the syncitium with cells and also forms the outpouchings that later become the chorionic villi.^[12]
Intermediate trophoblast is situated in the villi, the implantation site, and the chorionic sac.^[13]

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

Pathogenesis

Pathogenesis of the sub-types of gestational trophoblastic neoplasia is explained as follows:

Invasive Mole

Invasive mole is basically a benign tumor which arises from the invasion of the myometrium of a hydatidiform mole.^[14]
It may be preceded by a complete or partial molar pregnancy and it rarely metastasizes.^[15]^[16]^[17]
Invasive moles are more aggressive than complete or partial hydatidiform moles.^[18]
Although rarely metastatic, it can spread through the hematogenous route to the following organs:

Lungs (80% of the time)^[16]^[17]^[19]
Vagina (30%)^[16]^[17]^[19]
Pelvis (20%)^[16]^[17]^[19]
Liver (10%)^[16]^[17]^[19]
Brain (10%)^[16]^[17]^[19]
Other sites (< 5%)^[16]^[17]^[19]

Choriocarcinoma

Choriocarcinoma is a malignant tumor of the trophoblastic epithelium.^[20]
Cytotrophoblastic cells, functioning as stem cells, can undergo malignant transformation.^[21]
After the malignant transformation, the cells can differentiate into intermediate trophoblast and syncytiotrophoblast.^[22]
This mixture of cells can mimic normal development of a previllous blastocyst.^[23]
Choriocarcinoma can invade the uterine tissue and vasculature and spread to distant sites such as lungs, brain, liver, pelvis, vagina, spleen, intestines, and kidney.^[24]
Choriocarcinoma most commonly follows a molar pregnancy, spontaneous abortion, or ectopic pregnancy.
It can also follow a full-term pregnancy in less common scenarios.

Genetics

Invasive mole- diploid or aneuploid karyotype^[1]
Choriocarcinomas- aneuploid karyotype

Gross Pathology

Dark, shaggy, focally hemorrhagic & friable/necrotic-appearing^[3]
Invasive border

Microscopic Pathology

Gestational trophoblastic neoplasia classification^[1]


Types of Gestational Trophoblastic Neoplasia	Histopathological features

Invasive mole	The lesions are characterized by hyperplasia of cytotrophoblastic and syncytial elements and persistence of villous structures The lesions are characterized by trophoblastic invasion of the myometrium with identifiable villous structures
Choriocarcinoma	The lesions are characterized by columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels
Placental-site trophoblastic tumor	The tumor arising from the placental implantation site and resembles an exaggerated form of syncytial endometritis Trophoblastic cells infiltrate the myometrium, and there is vascular invasion
Epithelioid trophoblastic tumor	The tumor has a monomorphic cellular pattern of epithelioid cells and may resemble squamous cell cancer of the cervix when arising in the cervical canal

References

↑ ^1.0 ^1.1 ^1.2 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
↑ Woo J, Hsu C, Fung L, Ma H (1983). "Partial hydatidiform mole: ultrasonographic features". Aust N Z J Obstet Gynaecol. 23 (2): 103–7. PMID 6578773.
↑ ^3.0 ^3.1 Choriocarcinoma. librepathology.org. http://librepathology.org/wiki/index.php/Choriocarcinoma Accessed on October 8, 2015
↑ CHANG MC (October 1951). "Fertilizing capacity of spermatozoa deposited into the fallopian tubes". Nature. 168 (4277): 697–8. PMID 14882325.
↑ 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.
↑ AUSTIN CR (August 1952). "The capacitation of the mammalian sperm". Nature. 170 (4321): 326. PMID 12993150.
↑ Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.
↑ Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.
↑ 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.
↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
↑ Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.
↑ 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.
↑ https://www.cancer.gov
↑ ^16.0 ^16.1 ^16.2 ^16.3 ^16.4 ^16.5 ^16.6 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.
↑ ^17.0 ^17.1 ^17.2 ^17.3 ^17.4 ^17.5 ^17.6 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.
↑ https://www.cancer.gov
↑ ^19.0 ^19.1 ^19.2 ^19.3 ^19.4 ^19.5 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.
↑ https://www.cancer.gov
↑ Bishop BN, Edemekong PF. PMID 30571055. Missing or empty |title= (help)
↑ 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)
↑ 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)
↑ https://www.cancer.gov

Template:WH Template:WS

[abc-1] 1.0 ^1.1 ^1.2 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

[aaa-2] Woo J, Hsu C, Fung L, Ma H (1983). "Partial hydatidiform mole: ultrasonographic features". Aust N Z J Obstet Gynaecol. 23 (2): 103–7. PMID 6578773.

[ccc-3] 3.0 ^3.1 Choriocarcinoma. librepathology.org. http://librepathology.org/wiki/index.php/Choriocarcinoma Accessed on October 8, 2015

[pmid14882325-4] CHANG MC (October 1951). "Fertilizing capacity of spermatozoa deposited into the fallopian tubes". Nature. 168 (4277): 697–8. PMID 14882325.

[pmid14895481-5] 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.

[pmid12993150-6] AUSTIN CR (August 1952). "The capacitation of the mammalian sperm". Nature. 170 (4321): 326. PMID 12993150.

[7] Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.

[8] Moore, Keith (1988). Essentials of human embryology. Toronto Philadelphia Saint Louis, Mo: B.C. Decker C.V. Mosby Co. distributor. ISBN 9780941158978.

[pmid28698706-9] 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.

[10] Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.

[11] Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.

[12] Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.

[13] Moore, Keith (2016). The developing human : clinically oriented embryology. Philadelphia, PA: Elsevier. ISBN 9780323313384.

[Lurain2010-14] 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.

[15] ttps://www.cancer.gov

[pmid20673583-16] 16.0 ^16.1 ^16.2 ^16.3 ^16.4 ^16.5 ^16.6 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.

[pmid27743739-17] 17.0 ^17.1 ^17.2 ^17.3 ^17.4 ^17.5 ^17.6 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.

[18] ttps://www.cancer.gov

[pmid23999759-19] 19.0 ^19.1 ^19.2 ^19.3 ^19.4 ^19.5 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.

[20] ttps://www.cancer.gov

[pmid30571055-21] Bishop BN, Edemekong PF. PMID 30571055. Missing or empty |title= (help)

[pmid18059230-22] 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)

[pmid17613426-23] 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)

[24] ttps://www.cancer.gov

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