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Year : 2010  |  Volume : 6  |  Issue : 4  |  Page : 552-556

Unusual clinical and radiological presentation of metastatic choriocarcinoma to the brain and long-term remission following emergency craniotomy and adjuvant EMA-CO chemotherapy

Department of Neurosurgery, Sri Sathya Sai Institute of Higher Medical Sciences, EPIP Area, Whitefield, Bangalore, India

Date of Web Publication24-Feb-2011

Correspondence Address:
Ravi Dadlani
c/o Sri Sathya Sai Institute of Higher Medical Sciences, EPIP Area, Whitefield, Bangalore
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.77069

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 > Abstract 

Choriocarcinoma is the most malignant tumor of gestational trophoblast origin. Metastasis to brain is considered a poor prognostic indicator. Recent advances in adjuvant radiotherapy and chemotherapy have led to an excellent outcome of these patients. Craniotomy is indicated in selected cases with cerebral metastases. The authors report an interesting case of an aggressive choriocarcinoma with multiple metastases to the brain and viscera. The patient had radiological evidence of new lesions occurring almost every week while on the initial treatment and yet had a complete long-term remission with EMA-CO therapy. The interesting presentation, radiology and adjuvant therapies are discussed.

Keywords: EMA-CO, gestational trophoblastic tumors, intracerebral hemorrhage, metastasis

How to cite this article:
Dadlani R, Furtado SV, 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 Can Res Ther 2010;6:552-6

How to cite this URL:
Dadlani R, Furtado SV, 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 Can Res Ther [serial online] 2010 [cited 2022 Jul 6];6:552-6. Available from: https://www.cancerjournal.net/text.asp?2010/6/4/552/77069

 > Introduction Top

Seventy-eight percentage of stage IV patients (FIGO International Federation of Gynecology and Obstetrics) with choriocarcinoma can be expected to achieve complete or prolonged remission with multimodality therapy. [1] About 10% of choriocarcinomas metastasize to the brain. [2] However, prognosis is dismal in patients with intracerebral metastasis. [3] Cerebral metastases may present while on treatment or as a relapse after partial remission. [3] Due to the improvement of treatment protocols, current survival rate of choriocarcinoma has been greatly increased. [1] We are reporting an interesting case of a very aggressive choriocarcinoma who presented with intracranial hemorrhage and multiple cerebral metastases. She had in addition multiple metastases in extra neural structures. Complete long-term remission was achieved with emergency surgery and EMA-CO chemotherapy.

 > Case Report Top

A 25-year-old female patient, one year post partum, presented with features of raised intracranial pressure and left hemiplegia of 10 days history. On examination, she had bilateral papilledema and dense left hemiplegia. Magnetic resonance imaging (MRI) of the brain with gadolinium done a week prior to presentation revealed right parietal lobar hematoma. [[Figure 1] a, b] A repeat MRI [[Figure 1] c, d] at the time of presentation revealed an additional lesion in the right medial posterior frontal region. She underwent emergency craniotomy and evacuation of the hematoma. A working diagnosis of metastases to the brain was considered. A post-operative metastatic work up revealed multiple lesions in liver, pelvis and spleen [Figure 2]. Histopathology from the hematoma was inconclusive. A post-operative MRI revealed an additional lesion in the left medial thalamus [[Figure 3]a, b]. To obtain a conclusive diagnosis the medial frontal lesion was decompressed using intra-operative Stealth neuronavigation (Medtronic/Sofamor Danek, Minneapolis, MN)® . Histopathology revealed tissue with hemorrhage and numerous foam cells with large pleomorphic hyper chromatic nuclei which was compatible with the diagnosis of a choriocarcinoma [[Figure 4]a-c].
Figure 1: First MRI scan prior to presentation revealing a single subacute hemorrhage in the right parietal region (a) sagittal and (b) coronal T1W images. Contrast MR images at presentation revealed an additional right posterior frontal para-sagittal, non-contrast enhancing, isointense lesion, to the parenchyma on T1W images (c) coronal and (d) axial

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Figure 2: (a) Contrast MR imaging of the abdomen revealed multiple lesions in the liver and spleen (white arrows). Figure (b) revealed complete resolution of all visceral lesions on follow up

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Figure 3: MR images one week post op revealed (a) T2W coronal image showing the thalamic lesion (thin white arrow) and (b) T1W axial reveals the operative cavity (thick white arrow)

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Figure 4: Paraffin section showing (a) group of malignant cells (curved arrow) adjacent to the focus of hemorrhagic necrosis, (b) high power view showing round to oval cytotrophoblastic cells (straight arrow) with single vesicular nuclei and prominent nucleoli along with multinucleated syncytiotrophoblatic cell (curved arrow). Inset: Immunohistochemistry for epithelial membrane antigen (EMA) was positive in the cytotrophoblastic cells. [Hematoxylin and Eosin (a) ×40; (b) ×400] [Inset: Avidin Biotin Complex Immunoperoxidase Method ×400].

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A post second surgery MRI revealed yet another lesion in the left occipital pole with progression of the thalamic lesion [[Figure 5]a, b]. Thus, it would be seen that the patient had a new lesion every week prior to the commencement of the adjuvant therapy. She improved neurologically in the post-operative period and received 45 Gy radiotherapy (RT) with two opposing parallel portals under LINAC and 7 courses of EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine).
Figure 5: MR imaging post second surgery. T1W contrast images (a) axial and (b) sagittal revealed an additional lesion in the left occipital lobe (white arrow). T1W contrast MR images one year post op revealed (c) axial and (d) sagittal revealed the two operated sites with no evidence ofany lesions

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Her successive serum ß hCG levels are tabulated [Table 1] and graphically depicted in [Figure 6]. Imaging done after four months and subsequently one year after surgery revealed no evidence of any metastatic lesions [[Figure 2]b, [Figure 5]c, d].
Table 1: Successive free ß-hCG subunit assay in relation to duration from commencement of chemotherapy

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Figure 6: A logarithmic graphical representation of the serial ß hCG levels as a line graph has been depicted. The X axis denotes the time frame (in weeks) after commencement of the adjuvant therapy and the Y axis, the serum concentration of serial ß hCG levels. Individual values havebeen depicted

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The patient was in a FIGO stage IV [4] and had a WHO score of 22. Both indicating a high risk group and poor prognosis.

 > Discussion Top

Choriocarcinoma is a highly malignant tumor of the gestational trophoblast of the placenta. [5] The incidence is reported variously from 1 in 13, 000 to 50,000 pregnancies. [6] It has various clinical presentation ranging from the relatively benign hydatidiform mole to the more malignant invasive mole; placental site trophoblastic tumor to metastatic carcinoma. Approximately 25% of GTTs are identified after an abortion, molar pregnancy, 22.5% after a normal pregnancy and 2.5% after ectopic pregnancy. [7] After a non-molar pregnancy, a persistent tumor always has the histological pattern of choriocarcinoma in which tissue is often not obtained, and a precise diagnosis may therefore not be possible. The diagnosis is usually based on a rising human chorionic gonadotropin level or a plateau in the level that persists for more than three weeks. [1] Metastasis is most often associated with choriocarcinomas in contrast to other variants of the GTT. [1] The most common sites of metastasis are the lungs (in 80% of patients), vagina (30%), pelvis (20%) and liver (10%). Cerebral metastases occur in about 10% of the cases. [8] It is encountered almost exclusively in patients who have had a non-molar pregnancy with a protracted diagnosis. In about 50% of such patients, cerebral metastases may be the first manifestation of the tumor [5] and is uniformly considered as a poor prognostic factor. [1],[4]

GTT is a highly vascularized and the affinity of trophoblast for blood vessels ensures rapid hematogenous metastasis, hence known to bleed and cause hemorrhage which is the common cause of death in these conditions. [9]

ß hCG is a very good predictive indicator of prognosis and recurrence. Our patient revealed complete remission as evidenced by the ß hCG levels.

Emergency craniotomy is advocated in patients with intraracranial hemorrhage caused by metastatic choriocarcinoma and deteriorating neurological function.

This patient received EMACO regime as first line of chemotherapy after RT. A year of follow up revealed complete remission of the disease. There are case reports of choriocarcinoma with multiple metastases treated successfully by EMA-CO. [10]

Various other chemotherapy regimens have been tried such as MAC (methotrexate, actinomycin-D and cyclophosphamide) and Bagshawe's CHAMOCA (cyclophosphamide, hydroxyurea, actinomycin-D, methotrexate and vincristine) regime. [10] The cure rate achieved with the MAC regimen was 51% and 30% for primary and secondary treatment, respectively. [10] The CHAMOCA regimen was said to induce complete clinical remission in patients resistant to MAC. [10] In contrast, the EMA-CO regimen had 88% survival rate in high risk patients with 76% having no evidence of disease. [10]

This patient had several factors which have been relegated as implying poor prognosis including a preceding normal delivery, interval between pregnancy and diagnosis greater than 12 months, multiple distant metastases and very high ß hCG evels (>105 IU/L.). [1] This lady had a FIGO stage IV tumor and is in complete remission extending over 18 months.

 > Summary Top

Cerebral metastasis from choriocarcinoma is considered as a poor prognostic factor. The most common indication for surgical intervention is neurological deterioration from raised intracranial pressure due to a hemorrhage or tumor mass. Emergent surgery is live saving. The treatment of these tumors with craniotomy and excision followed by radiotherapy and newer chemotherapy regimes has improved survival even in stage IV patients.

 > References Top

1.Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med 1996;335:1740-8.  Back to cited text no. 1
2.Paradinas FJ, Browne P, Fisher RA, Foskett M, Bagshawe KD, Newlands E. A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions. Histopathology 1996;28:101-10.  Back to cited text no. 2
3.Semple PL, Denny L, Coughlan M, Soeters R, Van Wijk L. The role of neurosurgery in the treatment of cerebral metastases from choriocarcinoma: A report of two cases. Int J Gynecol Cancer 2004;14:157-61.  Back to cited text no. 3
4.FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009;105:3-4.  Back to cited text no. 4
5.Suresh TN, Santosh V, Shastry Kolluri VR, Jayakumar PN, Yasha TC, Mahadevan A, et al. Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis. Neurol India 2001;49:231-6.  Back to cited text no. 5
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6.Alveyn CG, Loehry CA. Hepatic metastases due to choriocarcinoma. Postgrad Med J 1988;64:941-2.  Back to cited text no. 6
7.Semer DA, Macfee MS. Gestational trophoblastic disease: Epidemiology. Semin Oncol 1995;22:109-12.  Back to cited text no. 7
8.Berkowitz RS, Goldstein DP. Pathogenesis of gestational trophoblastic neoplasms. Pathobiol Annu 1981;11:391-411.  Back to cited text no. 8
9.Kobayashi T, Kida Y, Yoshida J, Shibuya N, Kageyama N. Brain metastasis of choriocarcinoma. Surg Neurol 1982;17:395-403.  Back to cited text no. 9
10.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;59:235-8.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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