Article Data

  • Views 577
  • Dowloads 150


Open Access

Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature

  • E. Piura1
  • B. Piura2,*,

1Department of Obstetrics and Gynecology, Sapir Medical Center, Kfar-Saba, Sackler School of Medicine, University of Tel-Aviv

2Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva (Israel)

DOI: 10.12892/ejgo26312014 Vol.35,Issue 4,July 2014 pp.359-367

Published: 10 July 2014

*Corresponding Author(s): B. Piura E-mail: XXX


Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain – 80% and located in the cerebrum – 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body – 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) – 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.


Brain; Choriocarcinoma; GTD; GTN; Metastases.

Cite and Share

E. Piura,B. Piura. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature. European Journal of Gynaecological Oncology. 2014. 35(4);359-367.


[1] Lurain J.R.: “Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole”. Am. J. Obstet. Gynecol., 2010, 203, 531.

[2] Lurain J.R.: “Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia”. Am. J. Obstet. Gynecol., 2011, 204, 11.

[3] FIGO Oncology Committee: “FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee”. Int. J. Gynaecol. Obstet., 2002, 77, 285.

[4] Piura B.: “Women undergoing termination of pregnancy should be screened for gestational trophoblastic neoplasia”. Lancet., 2004, 364, 645.

[5] Semer D.A., Macfee M.S.: “Gestational trophoblastic disease: epidemiology”. Semin. Oncol., 1995, 22, 109.

[6] Steigrad S.J.: “Epidemiology of gestational trophoblastic diseases”. Best Pract. Res. Clin. Obstet. Gynaecol.: 2003, 17, 837.

[7] Soper J.T., Mutch D.G., Schink J.C., American College of Obstetricians and Gynecologists: “Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53”. Gynecol. Oncol., 2004, 93, 575.

[8] Langley R.R., Fidler I.J.: “The seed and soil hypothesis revisited –the role of tumor-stroma interactions in metastasis to different or-gans”. Int. J. Cancer, 2011, 128, 2527.

[9] Tosoni A., Ermani M., Brandes A.A.: “The pathogenesis and treatment of brain metastases: a comprehensive review”. Crit. Rev. Oncol. Hematol., 2004, 52, 199.

[10] Steeg P.S., Camphausen K.A., Smith Q.R.: “Brain metastases as preventive and therapeutic targets”. Nat. Rev. Cancer, 2011, 11, 352.

[11] Fidler I.J.: “The role of the organ microenvironment in brain metastasis”. Semin. Cancer Biol., 2011, 21, 107.

[12] Schouten L.J., Rutten J., Huveneers H.A., Twijnstra A.: “Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma”. Cancer, 2002, 94, 2698.

[13] Piura E, Piura B.: “Brain metastases from ovarian carcinoma”. ISRN Oncol., 2011, Article ID 527453, doi:10.5402/2011/527453.

[14] Piura E., Piura B.: “Brain metastases from endometrial carcinoma”. ISRN Oncol., 2012, Article ID 581749, doi:10.5402/2012/581749.

[15] Piura E., Piura B.: “Brain metastases from cervical carcinoma: overview of pertinent literature”. Eur. J. Gynaecol. Oncol., 2012, 33, 567.

[16] Zairi F., De Saint Denis T., Thines L., Bourgeois P., Lejeune J.P.: “Ruptured cerebral oncotic aneurysm from choriocarcinoma: report of two cases and review of the literature”. Acta Neurochir, (Wien)., 2011, 153, 353.

[17] Ishizuka T., Tomoda Y., Kaseki S., Goto S., Hara T., Kobayashi T.: “Intracranial metastasis of choriocarcinoma. A clinicopathologic study”. Cancer, 1983, 52, 1896.

[18] Kobayashi T., Kida Y., Yoshida J., Shibuya N., Kageyama N.: “Brain metastasis of choriocarcinoma”. Surg Neurol., 1982, 17, 395.

[19] Vaughan H.G., Howard R.G.: “lntracranial hemorrhage due to metastatic chorionepithelioma”. Neurology, 1962, 12, 771.

[20] Stilp T.J., Bucy P.C., Brewer J.I.: “Cure of metastatic choriocarcinoma of the brain”. JAMA, 1972, 221, 276.

[21] Weed J.C., Hammond C.B.: “Cerebral metastatic choriocarcinoma: Intensive therapy and prognosis”. Obstet. Gynecol., 1980, 55, 89.

[22] Barnes A.E., Liwnicz B.H., Schellhas H.F., Altshuler G., Aron B.S., Lippert W.A.: “Successful treatment of placental choriocarcinoma metastatic to brain followed by primary brain glioblastoma”. Gynecol. Oncol., 1982, 13, 108.

[23] Liu T.L., Deppe G., Chang Q.T., Tan T.T.: “Cerebral metastatic choriocarcinoma in the People’s Republic of China”. Gynecol. Oncol., 1983, 15, 166.

[24] van den Doel E.M., van Merriënboer F.J., Tulleken C.A.: “Cerebral hemorrhage from unsuspected choriocarcinoma”. Clin. Neurol. Neurosurg., 1985, 87, 287.

[25] Momma F., Beck H., Miyamoto T., Nagao S.: “Intracranial aneurysm due to metastatic choriocarcinoma”. Surg. Neurol., 1986, 25, 74.

[26] Ilancheran A., Ratnam S.S., Baratham G.: “Metastatic cerebral choriocarcinoma with primary neurological presentation”. Gynecol. Oncol., 1988, 29, 361.

[27] Koulos J.P., Hoffman J.S.: “Late brain recurrence of choriocarcinoma”. Gynecol. Oncol., 1988, 31, 467.

[28] Mates S.M., Yetsko R.A.: “Metastatic gestational choriocarcinoma: two cases. Ann. Emerg. Med., 1988, 17, 540.

[29] Rustin G.J., Newlands E.S., Begent R.H., Dent J., Bagshawe K.D.: “Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma”. J. Clin. Oncol., 1989, 7, 900.

[30] Kikuchi Y., Kita T., Tamai S., Nagata I.: “Choriocarcinoma with brain metastasis: report on two cases with long-term survivals”. Jpn. J. Clin. Oncol., 1990, 20, 306.

[31] Jones W.B., Wagner-Reiss K.M., Lewis J.L. Jr.: “Intracerebral choriocarcinoma”. Gynecol. Oncol., 1990, 38, 234.

[32] Wilkinson A.G., Sellar R.J.: “Case report: cerebral metastases from choriocarcinoma in the absence of detectable extracranial disease”. Clin. Radiol., 1991, 43, 278.

[33] Giannakopoulos G., Nair S., Snider C., Amenta P.S.: “Implications for the pathogenesis of aneurysm formation: metastatic choriocarcinoma with spontaneous splenic rupture. Case report and a review”. Surg. Neurol., 1992, 38, 236.

[34] Evans A.C. Jr., Soper J.T., Clarke-Pearson D.L., Berchuck A., Rodriguez G.C, Hammond C.B.: “Gestational trophoblastic disease metastatic to the central nervous system”. Gynecol. Oncol., 1995, 59, 226.

[35] Leslie M.D., Mangili G., Kemeny A.A., Newlands E.S.: “Gestational choriocarcinoma metastatic to the brain treated successfully by stereotactic radiosurgery and chemotherapy”. Clin. Oncol. (R. Coll. Radiol.), 1996, 8, 259.

[36] Schechter N.R., Mychalczak B., Jones W., Spriggs D.: “Prognosis of patients treated with whole-brain radiation therapy for metastatic gestational trophoblastic disease”. Gynecol. Oncol., 1998, 68, 183.

[37] Nozue A., Ichikawa Y., Minami R., Tsunoda H., Nishida M., Kubo T.: “Postpartum choriocarcinoma complicated by brain and lung metastases treated successfully with EMA/CO regimen”. Brit. J. Obstet. Gynaecol., 2000, 107, 1171.

[38] Suresh T.N., Santosh V., Shastry Kolluri V.R., Jayakumar P.N., Yasha T. C., Mahadevan A. et al.: “Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis”. Neurol. India, 2001, 49, 231.

[39] Mamelak A.N., Withers G.J., Wang X.: “Choriocarcinoma brain metastasis in a patient with viable intrauterine pregnancy. Case report”. J. Neurosurg., 2002, 97, 477.

[40] Balagopal P., Pandey M., Chandramohan K., Somanathan T., Kumar A.: “Unusual presentation of choriocarcinoma”. World J. Surg. Oncol., 2003, 1, 4.

[41] Picone O., Castaigne V., Ede C., Fernandez H.: “Cerebral metastases of a choriocarcinoma during pregnancy”. Obstet. Gynecol., 2003, 102, 1380.

[42] Ghaemmaghami F., Behtash N., Memarpour N., Soleimani K., Hanjani P., Hashemi F.A.: “Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors”. Int. J. Gynecol. Cancer, 2004, 14, 966.

[43] Hiramatsu Y., Masuyama H., Ishida M., Murakami K., Sakurai M.: “Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy”. Acta. Med. Okayama, 2005, 59, 235.

[44] Saad N., Tang Y.M., Sclavos E., Stuckey S.L.: “Metastatic choriocarcinoma: a rare cause of stroke in the young adult”. Australas Radiol., 2006, 50, 481.

[45] Soper J.T., Spillman M., Sampson J.H., Kirkpatrick J.P., Wolf J.K., Clarke-Pearson D.L.: “High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients”. Gynecol. Oncol., 2007, 104, 691.

[46] Sierra-Bergua B., Sánchez-Marteles M., Cabrerizo-García J.L., Sanjoaquin-Conde I.: “Choriocarcinoma with pulmonary and cerebral metastases”. Singapore Med. J., 2008, 49, e286.

[47] Chang I.B., Cho B.M., Park S.H., Yoon D.Y., Oh S.M.: “Metastatic choriocarcinoma with multiple neoplastic intracranial microaneurysms: case report”. J. Neurosurg., 2008, 108, 1014.

[48] Rocque B.G., Başkaya M.K.: “Spontaneous acute subdural hematoma as an initial presentation of choriocarcinoma: a case report”. J. Med. Case Rep., 2008, 2, 211.

[49] Verzár Z., Kövér E., Dóczi T., Kálmán E., Koppán M., Bódis J.: “Successful treatment of FIGO stage IV gestational choriocarcinoma occurring 2 months after delivery”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2008, 140, 275.

[50] Behtash N., Behnamfar F., Hamedi B., Ramezanzadeh F.: “Term delivery following successful treatment of choriocarcinoma with brain metastases, a case report and review of literature”. Arch. Gynecol. Obstet., 2009, 279, 579.

[51] Grisaru D., Reches A., Nimrod A.: “Mass effect: four months after a failed pregnancy, the patient was fatally ill”. Am. J. Obstet. Gynecol., 2009, 200, 214.

[52] Dadlani R., Furtado S.V., Ghosal N., Prasanna K.V., Hegde A.S.: “Unusual clinical and radiological presentation of metastatic choriocarcinoma to the brain and long-term remission following emergency craniotomy and adjuvant EMA-CO chemotherapy”. J. Cancer Res. Ther., 2010, 6, 552.

[53] Singhal M., Kudesia S., Bhat K., Arora P., Sharma A.: “Spontaneous intracerebral haemorrhage as initial presentation of gestational choriocarcinoma in a young woman: a case report and review of literature”. Internet J. Pathol., 2010, 10, 2.

[54] Brudie L.A., Ahmad S., Radi M.J., Finkler N.J.: “Metastatic choriocarcinoma in a viable intrauterine pregnancy treated with EMA-CO in the third trimester: a case report”. J. Reprod. Med., 2011, 56, 359.

[55] Shrestha P., Devkota U.P., Panth R.: “Metastatic choriocarcinoma masquerading as an intracerebral arteriovenous malformation bleed”. Internet J. Neurosurg., 2011, 7, 2.

[56] Tom M.I.: “Metastatic tumors of the brain”. Can. Med. Assoc. J., 1946, 54, 265.

[57] Chason J.L., Walker F.B., Landers J.W.: “Metastatic carcinoma in the central nervous system and dorsal root ganglia: a prospective autopsy study”. Cancer, 1963, 16, 781.

[58] Hunter K.M., Rewcastle N.B.: “Metastatic neoplasms of the brain stem”. Can. Med. Assoc. J., 1968, 98, 1.

[59] Zimm S., Wampler G.L., Stablein D., Hazra T., Young HF.: “Intracerebral metastases in solid-tumor patients: natural history and results of treatment”. Cancer, 1981, 48, 384.

[60] Le Chevalier T., Smith F.P., Caille P., Constans J.P., Rouesse J.G.: “Sites of primary malignancies in patients presenting with cerebral metastases. A review of 120 cases”. Cancer, 1985, 56, 880.

[61] Nussbaum E.S., Djalilian H.R., Cho K.H., Hall W.A.: “Brain metastases. Histology, multiplicity, surgery, and survival”. Cancer, 1996, 78, 1781.

[62] Lagerwaard F.J., Levendag P.C., Nowak P.J., Eijkenboom W.M., Hanssens P.E., Schmitz P.I.: “Identification of prognostic factors in patients with brain metastases: a review of 1292 patients”. Int. J. Radiat. Oncol. Biol. Phys., 1999, 43, 795.

[63] Kobayashi T., Kida Y., Yoshida J., Shibuya N., Kageyama N.: “Brain metastasis of choriocarcinoma”. Surg. Neurol., 1982, 17, 395.

[64] Athanassiou A., Begent R.H., Newlands E.S., Parker D., Rustin G.J., Bagshawe K.D.: “Central nervous system metastases of choriocarcinoma. 23 years’ experience at Charing Cross Hospital”. Cancer, 1983, 52, 1728.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time