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Metastatic cerebral choriocarcinoma with primary neurological presentation
GYNECOLOCIC
ONCOLOGY
29, 36 I-364 ( 1988)
Metastatic Cerebral Choriocarcinoma with Primary Neurological Presentation A. ILANCHERAN, M MED, MRCOG,” S. S. RATNAM, FRCS, FRCOG,* AND G. BARATHAM, MBBS. FRCSt *Drpartment
of’ Obstetrics rend (;vnec~olo,q~, Nrrtiontrl Universiry Hospitcrl. Sin,yapore; trnd fDrpnrtmrnt of‘ Neurosurgery. Tun TWX Scng Hospitnl. Singapore
Received September 8. 1986 Metastatic choriocarcinoma can present in bizarre fashions. Two cases with primary neurological presentations are reviewed. Cerebral metastases in choriocarcinoma generally denote a poor prognosis. However, in solitary metastases in the brain. craniotomy and excision followed by chemotherapy may be curative as illustrated by the following two cases. The first patient was diagnosed to have brain metastases It years after an evacuation of her molar pregnancy while the other patient developed cerebral choriocarcinoma 5 months following a spontaneous first trimester abortion. Both presented with neurological symptoms. Both patients are alive and well now, 9 and 5 years respectively after craniotomy and chemotherapy. A brief review of current considerations in the management of cerebral metastases in gestational trophoblastic disease is presented. Cc>1%X Academic Pre\\. Inc
INTRODUCTION
Common sites of metastases in gestational choriocarcinoma include the lung, vagina, liver, and brain [I]. Cerebral metastases are often multiple and their presence usually spells a grave prognosis for the patient. Despite several advances in modern chemotherapy, cerebral choriocarcinoma remains a largely lethal condition. We report here two cases of metastatic choriocarcinoma (one of whom had additional solitary lung metastasis) who presented primarily with neurological symptoms. Timely surgical intervention with craniotomy and excision of metastasis followed by chemotherapy cured both patients. CASE REPORT 1
A patient, W.K.S., 30-year-old Chinese female, para 1, was diagnosed to have a complete hydatidiform mole in March 1976. Evacuation by vacuum aspiration was performed. She was subsequently lost to follow up. In December 1977, she was admitted to the neurological unit with sudden loss of consciousness. A carotid angiogram done revealed a hemorrhagic focus in the left temporal lobe region. A left temporal lobectomy was performed and histology of the removed tissue 361 0090-8258188 $1.50 Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
362
ILANCHERAN,
RATNAM,
AND
BARATHAM
was reported as metastatic choriocarcinoma. She was referred to us for chemotherapy and was started on intravenous methotrexate (MTX). A chest X-ray done on admission showed a solitary metastasis in the right middle zone. There was no evidence of disease in the pelvis or elsewhere. Four days after starting chemotherapy, the patient developed Jacksonian and grand ma1 fits. Repeat carotid angiography revealed another hemorrhagic focus in the right frontoparietal region of the brain, which was then excised by a second craniotomy. Histology again revealed choriocarcinoma. She was subsequently started on a combination of MTX and actinomycin D (ACTD). After the second course of combined MTX and ACTD, the solitary lung nodule disappeared and the radioimmuoassay for the beta subunit HCG was reported as negative. She had three further courses of MTX and ACTD. She has remained disease free. Aphasic after the second craniotomy, the only defect she now has is a slight slurring of speech. CASE REPORT 2
L.C.H., a 26-year-old Chinese female, para 2, had an incomplete abortion, spontaneously, in January 1983, at 8 weeks of amenorrhea. On admission, she was found to have a uterus enlarged to 8 weeks and the cervical OSwas open. No other abnormalities were noted. Evacuation of the uterus was performed and normal products of conception was noted. Subsequent follow up at 6 weeks was unremarkable. She was discharged from further follow up. Almost exactly 5 months after her abortion, in June 1983, she was admitted to the neurosurgical unit with sudden drowsiness and a dense right hemiplegia. She was also grossly dysphasic. A CAT scan showed a large left frontal intracerebral hematoma. Cerebral angiography showed an arteriovenous shunt which was thought to be due to a congenital malformation. A craniotomy was performed and the lesion removed. At operation, the lesion was noted to be atypical of an angiomatous malformation. Histology revealed the lesion to be a choriocarcinoma. The patient was then referred for chemotherapy. The serum HCG at this time was 10,000 iu/liter. The chest X-ray was clear. She was started on combined therapy with intravenous MTX and ACTD with folinic acid rescue. She was continued on the same regime of chemotherapy at intervals of lo-14 days. At the end of the third course, the beta subunit HCG level became negative. She had two further courses of the drugs. The patient has remained disease free ever since and she had recovered almost completely from her hemiplegia. DISCUSSION
Cerebral metastasis in gestational trophoblastic disease generally denotes a poor prognosis. Often undiagnosed, these tumors undergo hemorrhage and necrosis when chemotherapy is started for the primary disease, and this probably contributes significantly to deaths during treatment [2]. A review of the methods of management of cerebral metastases in choriocarcinoma shows that total brain irradiation with
CASE
REPORTS
363
about 3000-4000 rads with vigorous combined chemotherapy appears to give the best results 13-51. Weed and Hammond [4] report a 50% survival rate with this regime. However, with solitary metastasis or in the presence of sudden hemorrhage, surgical intervention with craniotomy and excision of the affected area, followed by chemotherapy, may be life saving and curative. The two cases above illustrate this point very clearly. It was fortunate that despite the absence of a preoperative diagnosis of metastatic choriocarcinoma, these patients survived intracerebral hemorrhage. In fact, the first patient survived two such episodes. As far as we know, this probably is the first reported case of a patient who had undergone and survived two successive craniotomies for cerebral choriocarcinoma. She also had pulmonary metastases which resolved with chemotherapy. Several points emerge from the study of these two cases. First, any patient in the reproductive age group with a history of a previous pregnancy, when presenting with sudden neurological symptoms, should be suspected of having metastatic choriocarcinoma. Only a high index of suspicion will enable the diagnosis to be made. A simple pregnancy test will often confirm the suspicion and definitive treatment can be instituted promptly. Second, although pulmonary metastases often precede cerebral spread, patients may present without any pulmonary disease as was the situation in the second case. This has been noted by others [4,6]. Third, it raises the question of the type of chemotherapy these patients require and the route by which the drugs should be administered. The presence of cerebral metastases places a patient in the very high-risk group, and it is usually recommended that such patients be treated with the multidrug regime of Bagshawe [7] or with a regime of triple chemotherapy [S]. It is well known that patients with poor prognosis disease do much better with multiple agent regimens initially and rescue with multiple agents after primary single agents have poor results. Currently, our regimen for high risk patients consists of combination chemotherapy with etoposide, methotrexate, and actinomycin D (EMA). It is probably not necessary to use the MTX intrathecally even in proven cases of cerebral choriocarcinoma. High dose systemic therapy achieves the same results as our experience suggests and as Surwit and Hammond have demonstrated 191. Experimentally, choriocarcinoma implants in the central nervous system produce an increased premeability of the blood-brain barrier [lo] and a big intravenous dose of a chemotherapeutic agent is certain to reach the central nervous system. In conclusion, it is recommended that all patients who have persistent evidence of trophoblastic disease should have a thorough search for sites of possible metastases. A CAT scan of the brain should be routine and is vital if metastases are to be detected before start of the chemotherapy. Optimum results in patients with cerebral metastases are obtained when the whole brain is irradiated and combination chemotherapy concurrently given. However, in patients with solitary cerebral metastasis presenting acutely and in those not responding to chemotherapy, prompt craniotomy is life saving and may reduce the duration and dosage of chemotherapy.
364
ILANCHERAN,
RATNAM,
AND BARATHAM
REFERENCES 1. Ilancheran, A., and Ratnam, S. S. Recent advances in the management of gestational trophoblastic disease, Ann. Acad. Med. 11, 539-544 (1982). 2. Begent, R. H., and Bagshawe, K. D. Treatment of advanced trophoblastic disease, in C. T. Griffiths and A. H. Fuller (Eds), Gynecological oncology, Martinus Nijhoff, Boston (1983). 3. Brace, K. C. The role of irradiation in the treatment of metastatic trophoblastic disease, Radiology 91, 540-544 (1968).
4. Weed, J. C., and Hammond, C. B. Cerebral metastatic choriocarcinoma: Intensive therapy and prognosis, Obstet. Gynecol. 55, 89-94 (1980). 5. Ishizuka, T., Tomoda, Y., Kaseki, S., Goto, S., Hara, T., and Kobayashi, T. Intracranial metastasis of choriocarcinoma-A clinicopathological study, Cancer 52, 1896-1903 (1983). 6. Athanassiou, A., Begent, R. H., Newlands, E. S., Parker, D., Rustin, G. J. S., and Bagshawe, K. D. Central nervous system metastases of choriocarcinoma: 23 years of experience at Charing Cross Hospital, Cancer 52, 1728-1735 (1983). 7. Bagshawe, K. D. Treatment of trophoblastic tumours, Ann. Acad. Med. 5, 273-279 (1976). 8. Goldstein, D. P., and Berkowitz, R. S. Management of gestational trophoblastic neoplasms, Cur. Prob. Obstet. Gynecol. 3, 3 (1980). 9. Surwit, E. A., and Hammond, C. B. Treatment of metastatic trophoblastic disease with poor prognosis, Obstet. Gynecol. 55, 565-570 (1980). 10. Ausman, J. I., Levin, V. A., Brown, W. E., Rail, D. P., and Fenstermacher, J. D. Brain tumour chemotherapy, J. Neurosurg. 46, 155-163 (1977).
ONCOLOGY
29, 36 I-364 ( 1988)
Metastatic Cerebral Choriocarcinoma with Primary Neurological Presentation A. ILANCHERAN, M MED, MRCOG,” S. S. RATNAM, FRCS, FRCOG,* AND G. BARATHAM, MBBS. FRCSt *Drpartment
of’ Obstetrics rend (;vnec~olo,q~, Nrrtiontrl Universiry Hospitcrl. Sin,yapore; trnd fDrpnrtmrnt of‘ Neurosurgery. Tun TWX Scng Hospitnl. Singapore
Received September 8. 1986 Metastatic choriocarcinoma can present in bizarre fashions. Two cases with primary neurological presentations are reviewed. Cerebral metastases in choriocarcinoma generally denote a poor prognosis. However, in solitary metastases in the brain. craniotomy and excision followed by chemotherapy may be curative as illustrated by the following two cases. The first patient was diagnosed to have brain metastases It years after an evacuation of her molar pregnancy while the other patient developed cerebral choriocarcinoma 5 months following a spontaneous first trimester abortion. Both presented with neurological symptoms. Both patients are alive and well now, 9 and 5 years respectively after craniotomy and chemotherapy. A brief review of current considerations in the management of cerebral metastases in gestational trophoblastic disease is presented. Cc>1%X Academic Pre\\. Inc
INTRODUCTION
Common sites of metastases in gestational choriocarcinoma include the lung, vagina, liver, and brain [I]. Cerebral metastases are often multiple and their presence usually spells a grave prognosis for the patient. Despite several advances in modern chemotherapy, cerebral choriocarcinoma remains a largely lethal condition. We report here two cases of metastatic choriocarcinoma (one of whom had additional solitary lung metastasis) who presented primarily with neurological symptoms. Timely surgical intervention with craniotomy and excision of metastasis followed by chemotherapy cured both patients. CASE REPORT 1
A patient, W.K.S., 30-year-old Chinese female, para 1, was diagnosed to have a complete hydatidiform mole in March 1976. Evacuation by vacuum aspiration was performed. She was subsequently lost to follow up. In December 1977, she was admitted to the neurological unit with sudden loss of consciousness. A carotid angiogram done revealed a hemorrhagic focus in the left temporal lobe region. A left temporal lobectomy was performed and histology of the removed tissue 361 0090-8258188 $1.50 Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
362
ILANCHERAN,
RATNAM,
AND
BARATHAM
was reported as metastatic choriocarcinoma. She was referred to us for chemotherapy and was started on intravenous methotrexate (MTX). A chest X-ray done on admission showed a solitary metastasis in the right middle zone. There was no evidence of disease in the pelvis or elsewhere. Four days after starting chemotherapy, the patient developed Jacksonian and grand ma1 fits. Repeat carotid angiography revealed another hemorrhagic focus in the right frontoparietal region of the brain, which was then excised by a second craniotomy. Histology again revealed choriocarcinoma. She was subsequently started on a combination of MTX and actinomycin D (ACTD). After the second course of combined MTX and ACTD, the solitary lung nodule disappeared and the radioimmuoassay for the beta subunit HCG was reported as negative. She had three further courses of MTX and ACTD. She has remained disease free. Aphasic after the second craniotomy, the only defect she now has is a slight slurring of speech. CASE REPORT 2
L.C.H., a 26-year-old Chinese female, para 2, had an incomplete abortion, spontaneously, in January 1983, at 8 weeks of amenorrhea. On admission, she was found to have a uterus enlarged to 8 weeks and the cervical OSwas open. No other abnormalities were noted. Evacuation of the uterus was performed and normal products of conception was noted. Subsequent follow up at 6 weeks was unremarkable. She was discharged from further follow up. Almost exactly 5 months after her abortion, in June 1983, she was admitted to the neurosurgical unit with sudden drowsiness and a dense right hemiplegia. She was also grossly dysphasic. A CAT scan showed a large left frontal intracerebral hematoma. Cerebral angiography showed an arteriovenous shunt which was thought to be due to a congenital malformation. A craniotomy was performed and the lesion removed. At operation, the lesion was noted to be atypical of an angiomatous malformation. Histology revealed the lesion to be a choriocarcinoma. The patient was then referred for chemotherapy. The serum HCG at this time was 10,000 iu/liter. The chest X-ray was clear. She was started on combined therapy with intravenous MTX and ACTD with folinic acid rescue. She was continued on the same regime of chemotherapy at intervals of lo-14 days. At the end of the third course, the beta subunit HCG level became negative. She had two further courses of the drugs. The patient has remained disease free ever since and she had recovered almost completely from her hemiplegia. DISCUSSION
Cerebral metastasis in gestational trophoblastic disease generally denotes a poor prognosis. Often undiagnosed, these tumors undergo hemorrhage and necrosis when chemotherapy is started for the primary disease, and this probably contributes significantly to deaths during treatment [2]. A review of the methods of management of cerebral metastases in choriocarcinoma shows that total brain irradiation with
CASE
REPORTS
363
about 3000-4000 rads with vigorous combined chemotherapy appears to give the best results 13-51. Weed and Hammond [4] report a 50% survival rate with this regime. However, with solitary metastasis or in the presence of sudden hemorrhage, surgical intervention with craniotomy and excision of the affected area, followed by chemotherapy, may be life saving and curative. The two cases above illustrate this point very clearly. It was fortunate that despite the absence of a preoperative diagnosis of metastatic choriocarcinoma, these patients survived intracerebral hemorrhage. In fact, the first patient survived two such episodes. As far as we know, this probably is the first reported case of a patient who had undergone and survived two successive craniotomies for cerebral choriocarcinoma. She also had pulmonary metastases which resolved with chemotherapy. Several points emerge from the study of these two cases. First, any patient in the reproductive age group with a history of a previous pregnancy, when presenting with sudden neurological symptoms, should be suspected of having metastatic choriocarcinoma. Only a high index of suspicion will enable the diagnosis to be made. A simple pregnancy test will often confirm the suspicion and definitive treatment can be instituted promptly. Second, although pulmonary metastases often precede cerebral spread, patients may present without any pulmonary disease as was the situation in the second case. This has been noted by others [4,6]. Third, it raises the question of the type of chemotherapy these patients require and the route by which the drugs should be administered. The presence of cerebral metastases places a patient in the very high-risk group, and it is usually recommended that such patients be treated with the multidrug regime of Bagshawe [7] or with a regime of triple chemotherapy [S]. It is well known that patients with poor prognosis disease do much better with multiple agent regimens initially and rescue with multiple agents after primary single agents have poor results. Currently, our regimen for high risk patients consists of combination chemotherapy with etoposide, methotrexate, and actinomycin D (EMA). It is probably not necessary to use the MTX intrathecally even in proven cases of cerebral choriocarcinoma. High dose systemic therapy achieves the same results as our experience suggests and as Surwit and Hammond have demonstrated 191. Experimentally, choriocarcinoma implants in the central nervous system produce an increased premeability of the blood-brain barrier [lo] and a big intravenous dose of a chemotherapeutic agent is certain to reach the central nervous system. In conclusion, it is recommended that all patients who have persistent evidence of trophoblastic disease should have a thorough search for sites of possible metastases. A CAT scan of the brain should be routine and is vital if metastases are to be detected before start of the chemotherapy. Optimum results in patients with cerebral metastases are obtained when the whole brain is irradiated and combination chemotherapy concurrently given. However, in patients with solitary cerebral metastasis presenting acutely and in those not responding to chemotherapy, prompt craniotomy is life saving and may reduce the duration and dosage of chemotherapy.
364
ILANCHERAN,
RATNAM,
AND BARATHAM
REFERENCES 1. Ilancheran, A., and Ratnam, S. S. Recent advances in the management of gestational trophoblastic disease, Ann. Acad. Med. 11, 539-544 (1982). 2. Begent, R. H., and Bagshawe, K. D. Treatment of advanced trophoblastic disease, in C. T. Griffiths and A. H. Fuller (Eds), Gynecological oncology, Martinus Nijhoff, Boston (1983). 3. Brace, K. C. The role of irradiation in the treatment of metastatic trophoblastic disease, Radiology 91, 540-544 (1968).
4. Weed, J. C., and Hammond, C. B. Cerebral metastatic choriocarcinoma: Intensive therapy and prognosis, Obstet. Gynecol. 55, 89-94 (1980). 5. Ishizuka, T., Tomoda, Y., Kaseki, S., Goto, S., Hara, T., and Kobayashi, T. Intracranial metastasis of choriocarcinoma-A clinicopathological study, Cancer 52, 1896-1903 (1983). 6. Athanassiou, A., Begent, R. H., Newlands, E. S., Parker, D., Rustin, G. J. S., and Bagshawe, K. D. Central nervous system metastases of choriocarcinoma: 23 years of experience at Charing Cross Hospital, Cancer 52, 1728-1735 (1983). 7. Bagshawe, K. D. Treatment of trophoblastic tumours, Ann. Acad. Med. 5, 273-279 (1976). 8. Goldstein, D. P., and Berkowitz, R. S. Management of gestational trophoblastic neoplasms, Cur. Prob. Obstet. Gynecol. 3, 3 (1980). 9. Surwit, E. A., and Hammond, C. B. Treatment of metastatic trophoblastic disease with poor prognosis, Obstet. Gynecol. 55, 565-570 (1980). 10. Ausman, J. I., Levin, V. A., Brown, W. E., Rail, D. P., and Fenstermacher, J. D. Brain tumour chemotherapy, J. Neurosurg. 46, 155-163 (1977).