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 »  Material and methods
 »  Results
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Year : 2001  |  Volume : 49  |  Issue : 3  |  Page : 231-6

Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis.

Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore-560 029, India.

Correspondence Address:
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore-560 029, India.

  »  Abstract

A retrospective analysis of clinicopathological data of 10 patients with clinically unsuspected cerebral metastatic choriocarcinoma was carried out. All patients were young adult females. History of preceding pregnancy/abortion was forthcoming in 5 cases but none had a prior history of abnormal gestation. Features of raised intracranial tension followed by hemiparesis were the commonest presenting symptoms. A clinicoradiologic diagnosis of intracerebral haemorrhagic mass, either primary or secondary to tumour bleed, cortico-venous thrombosis or arteriovenous malformation, was entertained in 8 out of 10 cases. In other two cases, ring enhancing lesions prompted the diagnosis of granulomatous masses. Eight patients were operated upon, of whom two died after short hospital stay, and were autopsied. All had haemorrhagic masses noted at surgery/autopsy. Accurate diagnosis of metastatic choriocarcinoma was established only by histologic examination of these haemorrhages. This report emphasizes the importance of considering metastatic choriocarcinoma as an important differential diagnosis of haemorrhagic intracerebral lesions in women of child bearing age group. Measurement of serum/CSF level of HCG in suspected cases helps to implement early therapy. The diagnostic value of histopathologic examination of surgically resected blood clots in determining aetiology of intracerebral haemorrhagic masses is highlighted.

How to cite this article:
Suresh T N, Santosh V, Shastry Kolluri V R, Jayakumar P N, Yasha T C, Mahadevan A, Shankar S K. Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis. Neurol India 2001;49:231

How to cite this URL:
Suresh T N, Santosh V, Shastry Kolluri V R, Jayakumar P N, Yasha T C, Mahadevan A, Shankar S K. Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis. Neurol India [serial online] 2001 [cited 2023 Nov 29];49:231. Available from:

   »   Introduction Top

It is known that primary and metastatic intracranial neoplasms can sometimes cause intracerebral haemorrhage, which in about half of the cases may be the first manifestation of tumour.[1] However, on a general basis, metastatic tumours bleed more often than primary CNS neoplasms. Choriocarcinoma, bronchial carcinoma, melanoma and renal cell carcinoma have been reported to be the metastatic tumours more often responsible for intracerebral haemorrhage,[2],[3],[4] apart from lymphoreticular malignancy. Gestational choriocarcinoma is a rare tumour in the West, but its incidence is reported to be frequent in south east Asia. One report from India quotes the incidence of choriocarcinoma as 1 in 2958 pregnancies.[5] Inspite of the remarkable improvement in the treatment of choriocarcinoma, mortality is still significant; cranial metastasis being responsible for death in nearly 50% of cases.[6] While metastasising within the central nervous system, these tumours are known for their tendency to produce haematoma and intracranial haemorrhages,[6] causing the morbidity and mortality observed in these patients. To the best of our knowledge, there is no report from India describing unsuspected metastasising choriocarcinoma to brain.

   »   Material and methods Top

Ten consecutive cases of choriocarcinoma metastasising to the brain, seen between 1991 and 1999 at National Institute of Mental Health and Neurosciences (NIMHANS) were retrospectively analysed. The clinical records and the radiological features were reviewed. Eight surgically resected specimens and two brains collected at autopsy were examined pathologically. A clinico-radiological and pathological correlation was attempted.

   »   Results Top

Clinical details of the 10 patients are summarised in [Table I]. All the patients were females in the child bearing age group (17-35 years). They presented with varied neurological symptoms. Sudden onset of headache, vomiting and convulsion were the most frequent initial symptoms noted in 7 cases, followed by hemiparesis and sensory disturbances in 3 cases. A history of preceding pregnancy/abortion was forthcoming in 5 cases (50%). No other significant past history was noted. A clinical impression of cerebral venous thrombosis (CVT) (2), tuberculous meningitis (2), tumour (3), haematoma (2) and arterio venous malformation (AVM) with bleed (1) was made and the patients were investigated.
Cranial CT scan was available in all cases. A well defined, hyperdense lesion with significant perilesional oedema and mass effect was the most common finding [Figure. 1a]. In majority of cases (8/10), the lesions were interpreted as haemorrhagic masses. Two cases (No.3 and 10) revealed well defined contrast enhancing ring lesions, and a radiological diagnosis of granuloma was considered [Figure. 1b]. Lesions were observed in parietal (7) and frontal (7) regions followed by occipital (1) and temporal (1) lobe. Majority of the patients had solitary lesions
(7 cases), however 3 cases showed multiple lesions. Chest X-ray done in 5 cases did not show metastatic lesion in the lung.
Surgical resection and evacuation of haemorrhagic lesion was carried out in [eight] cases. The lesions were haemorrhagic in all cases. They were deep seated in cerebral parenchyma in 6 and were reaching the surface in 2 cases. A good plane of cleavage between the lesion and surrounding parenchyma was evident in all. Extension of the haemorrhage into the sub arachnoid space, breaching the cortex was noted in one case. Gross examination of the surgically resected material revealed mainly blood clots. In two cases, partial autopsy confined to removal of the brain was carried out for definitive pathological diagnosis. Serial coronal slices of cerebral hemisphere revealed supratentorial haematomas in both the cases. One case (No. 8) revealed lobar haematoma in the left frontal lobe extending posteriorly into the parietal lobe, reaching the surface with a small patch of subarachnoid haemorrhage in the left sylvian fissure. In the other case (No. 10), two well circumscribed haemorrhagic deposits, one in the right parietal convexity [Figure. 2] and the other in the right occipital lobe were noted. Marked perilesional oedema and shift of midline structure to opposite site was evident in both.
Histological examination revealed extensive haemorrhage with peripherally placed tumour cells [Figure. 3a]. The tumour was predominantly composed of solid sheets of cytotrophoblasts surrounded and separated by syncytiotrophoblasts giving a characteristic biphasic or plexiform arrangement [Figure. 3b]. The tumour cells exhibited significant cellular and nuclear atypia. Mitosis was very brisk, with many cells revealing abnormal mitotic [Figureures]. Presence of haemosiderin laden macrophages and/or organisation of blood clot was observed in all the cases. In all cases, the tumour was highly vascular with proliferating thin walled vessels. Necrotic areas were seen in close proximity to viable tumour tissue in 5 cases. The surrounding brain parenchyma revealed host reaction in the form of mononuclear inflammatory cell infiltration (4 cases) and gliosis (3 cases). In one autopsied case, tumour emboli were seen within brain parenchymal vessels close to areas of necrosis [Figure. 3c]. The histological features were diagnostic of metastatic choriocarcinoma. Six patients were referred to oncology institute for chemotherapy. Four patients died in the hospital (2 patients before surgery and 2 after surgery).

   »   Discussion Top

Choriocarcinoma is a malignant tumour of cytotrophoblasts and syncytiotrophoblasts, which can arise in any type of gestation and the types of preceding pregnancy includes most often hydatiform mole followed by normal pregnancy, spontaneous abortion or ectopic pregnancy.[7] In our series, history of pregnancy or abortion was available only in 5 cases. However, there was no known case of choriocarcinoma. Most cases reported in the literature as metastatic choriocarcinoma with unknown primary, have been reported to have arisen in the placenta from prior normal pregnancy. Primary placental choriocarcinoma can easily be missed due to their small size.[7] Choriocarcinoma is known to spread by the vascular route and often metastasises to the central nervous system (CNS). The incidence of CNS metastasis from gestational choriocarcinoma has been reported to range from 3% to 28%.[8],[9],[10],[11],[12] This wide range of incidence is probably due to varying referral and follow up patterns at different centres. At NIMHANS, choriocarcinoma formed 4.0% of all brain metastatic tumours (10/216) during the study period. Despite the fact that prognosis of primary disease has improved greatly with effective chemotherapeutic agents, presence of metastasis in the CNS is considered an adverse prognostic factor.[8] However, recent advances in diagnostic procedures and operative techniques have aided in early detection of CNS metastasis of choriocarcinoma and hence promises a more favourable prognosis of the disease. In two cases (no.4 and 8), a clinical diagnosis of cerebral venous thrombosis (CVT) was considered because CVT is one of the most common causes of stroke in young. In a study of 645 cases of stroke in the young seen over 5 years at NIMHANS, 30.5% had CVT which commonly occured during the puerperal period.[13],[14]
CT scan showed haemorrhagic lesions with significant perilesional oedema and mass effect in most of the cases. These radiological findings are often mistaken for primary intracerebral haemorrhage due to local causes, rather than tumour metastasis, particularly when there is no clue for a primary tumour in the patient. Chest X-ray done in 5 cases failed to reveal any metastatic deposit. Ishizuka et al[15] reported pulmonary metastasis in 27 out of 28 patients with brain metastasis in patients with gestational choriocarcinoma. However, metastatic cerebral choriocarcinoma without pulmonary metastasis has been reported in literature.[16],[17] This illustrates the need to consider the diagnosis of metastatic cerebral choriocarcinoma even if pulmonary examination is negative.
The striking point in our cases was that none of these patients were known cases of gestational choriocarcinoma. They presented primarily with neurological symptoms. Accurate diagnosis was established only after histological examination of the resected blood clots. Due to the relatively low incidence of brain tumour as the cause for the intracerebral haematoma, pathological examination of the surgically removed blood clots from patients with intracerebral haemorrhage of uncertain aetiology is not always performed. Jellinger reported, 61 angiomas, 12 tumours, and 5 angiitides, in a series of 112 operated cases of intracerebral haemorrhage, on histologic examination.[18] Hinton et al, in a series of 84 cases of spontaneous intracerebral haemorrhage could make the anatomical diagnosis in 37 cases. In 14 cases the specific aetiology of the haemorrhage, which included primary and metastatic tumour, amyloid angiopathy and abscess could be determined.[19] Van den Doel et al[20] reported a case of metastatic choriocarcinoma by cytological examination of the intracerebral haematoma. All these authors have stressed the importance of histopathological examination of surgically removed blood clots, in determining the aetiology. Our study further supports the value of histopathological examination of surgically excised blood clot in determining the aetiology of intracerebral haemorrhages. Suction evacuation of the cerebral haemorrhagic mass may cause loss of material for histopathological evaluation and thus may miss the diagnosis. It is important to examine the tissue from the wall of haematoma to exclude a haemorrhagic metastasis. In the present study, 7 cases had a solitary metastatic deposit. The lesion was supratentorial in location in all the cases and fronto- parietal region was the preferred site (7/10), as reported in earlier studies.[16],[21]
Radioimmunoassay of beta human chorionic gonadotrophin (HCG) should be used to confirm the diagnosis. It is estimated that serum : CSF ration of less than 60:1 is a sensitive indicator of metastasis in the brain.[16] The prognosis of choriocarcinoma with cerebral metastasis has improved considerably with time. Earlier, only about one third of cases presenting early with CNS presentation survived and none with late CNS presentation. After 1974, intrathecal prophylaxis with methotrexate given in high risk patients has improved the overall survival to 80% in the CNS presentation group and 25% in the late CNS group.[16] Surgical treatment is the method of choice for brain metastasis in patients displaying rapidly deteriorating signs. A better prognosis will be achieved by a combination of surgical removal, chemotherapy and irradiation.[21] However, the difficulties in the diagnosis and management of unsuspected gestational choriocarcinoma presenting with intra cerebral haemorrhages continue. In an unsuspected case, heparin therapy with a clinical diagnosis of cerebral venous thrombosis in post partum period may lead to catastrophic haemorrhage. A circumscribed haemorrhagic lesion with perilesional oedema in young women of reproductive age group should raise the suspicion of metastatic choriocarcinoma. Measurement of HCG in CSF and serum further helps to implement early therapy and effective management of these patients. Histopathological examination of the surgically removed blood clots remains the corner stone for accurate diagnosis.


  »   References Top

1.Wakai S, Yamakawa K, Manaka S et al : Spontaneous intracranial haemorrhage caused by brain tumours. Its incidence and clinical significance. Neurosurgery 1982; 10 : 437-444.   Back to cited text no. 1    
2.Kardzioka D, Bernstein M, Resch L et al : Significance of haemorrhage in brain tumour. Clinicopathological study. J Neurosurg 1987; 67 : 852-857.   Back to cited text no. 2    
3.Mandybur TI : Intracranial haemorrhage in metastatic tumours. Neurology 1977; 650.   Back to cited text no. 3    
4.Scott M : Spontaneous intracerebral haematoma caused by cerebral neoplasm. J Neurosurg 1975; 42 : 338.   Back to cited text no. 4    
5.Krishna Menon MK, Palaniappan B : Diseases and abnormalities of the fetal membrane and placenta. In : Mudaliar and Menon's Clinical Obstetrics : Oriental longman 9th edition, 1990; 200.   Back to cited text no. 5    
6.Ade Loye A, Osuntokun BO, Hndrickse JP et al : The neurology of metastatic choriocarcinoma of uterus. J Neurol Sci 1972; 16 : 315-329.   Back to cited text no. 6    
7.Redline RW, Fadi W, Abdul-Karim : Pathology of gestational trophoblastic disease. Seminars in Oncology 1995; 22 : 96-109.   Back to cited text no. 7    
8.Bagshawe KD : Risk and prognostic factors in trophoblastic neoplasia. Cancer 1976; 38 : 1373-1385.   Back to cited text no. 8    
9.Weed JC, Hammond CB : Cerebral metastatic choriocarcinoma: Intensive therapy and prognosis. Obstetrics and Gynecology 1980; 55 : 89-94.   Back to cited text no. 9    
10.Stip TJ, Bucy PC, Brewer Jl : Cure of metastatic choriocarcinoma of the brain. JAMA 1972; 221 : 276-279.   Back to cited text no. 10    
11.Park WW, Lees JC : Choriocarcinoma : A general review with analysis of 516 cases. Arch Pathol 1950; 49 : 205-241.   Back to cited text no. 11    
12.Vagughan HG, Howard RG : Intracranial haemorrhage due to metastatic chiorionepithelioma. Neurology 1962; 12 : 771-777.   Back to cited text no. 12    
13.Nagaraja D, Taly AB : Stroke in young. In : Sinha KK, Chandra P, Eds. Ranchi: NSI Publication. Progress in Clinical Neurosciences 1988; 1 : 129-145.   Back to cited text no. 13    
14.Nagaraja D, Taly AB, Sarala Das : Puerperal cerebral venous thrombosis. In : Progress in Clinical Neurosciences1987; 1 : 324-338.   Back to cited text no. 14    
15.lszhizuka T, Tomoda Y, Hesaki S et al : Intracranial metastasis of choriocarcinoma - A clinico pathological study. Cancer1983; 52 : 1896-1903.   Back to cited text no. 15    
16.Athanassiou A, Begent RKJ, Newlands ES et al : Central nervous system metastasis of choriocarcinoma - 23 year experience at Charing Cross Hospital. Cancer 1983; 52 : 1728-1735.   Back to cited text no. 16    
17.Fisher RG, Bennion S, Frimeer D et al : Metastatic cerebral choriocarcinoma without pelvic or pulmonary metastases. Surg Neurol 1979; 11 : 57-59.   Back to cited text no. 17    
18.Jellinger K : Spontaneous intracerebral haematomas pathology and aetiology of supratentorial haemorrhage. In : Advances in diagnosis and therapy. Pia HW, Langnaid C, Zierski J (eds.). Springer Verlag, Stuttgart. 1980; 51 : 131-135.   Back to cited text no. 18    
19.Hinton DR, Dolan E, Ander AF : The value of histopathological examination of surgically removed blood clot in determining the etiology of spontaneous intracerebral haemorrhage. Stroke 1984; 15 : 517-520.   Back to cited text no. 19    
20.Vanden Doel EMH, Van Merri Enboer FJJM, Tullekar CAF : Cerebral haemorrhage from unsuspected choriocarcinoma. Clinical Neurology and Neurosurgery 1985; 87 : 287-290.   Back to cited text no. 20    
21.Kobayashi T, Kida Y, Yoshida J et al : Brain metastasis of choriocarcinoma. Surg Neurol 1982; 17 : 395-403.   Back to cited text no. 21    


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