236
Surg Neurol 1992 ;38 :236-40
Implications for the Pathogenesis of Aneurysm Formation : Metastatic Choriocarcinoma with Spontaneous Splenic Rupture . Case Report and a Review George Giannakopoulos, M .D., Somnath Nair, M .D., Cameron Snider, and Peter S . Amenta, M.D., Ph.D. Departments of Neurosurgery and Pathology, Hahnemann University, Philadelphia, Pennsylvania
Giannakopoulos G, Nair S, Snider C, Amenta PS . Implications for the pathogenesis of aneurysm formation : metastatic choriocarcinoma with spontaneous splenic rupture . Case report and a review. Surg Neurol 1992 ;38 :236-40 . We report a case of ruptured intracranial aneurysm from metastatic choriocarcinoma in a patient presenting with intracerebral hemorrhage . Operative evacuation of the hematoma with clipping of a distal right middle cerebral artery aneurysm was performed . Postoperatively, the patient developed hypovolemic shock from spontaneous splenic rupture. Histopathologic examination of the cerebral aneurysm showed choriocarcinoma invading the vessel wall . Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral or subarachnoid hemorrhage in women of child-bearing age . KEY
WORDS :
IntraCranial
aneurysm ; Choriocarcinoma ;
Splenic rupture
Choriocarcinoma is a rare, highly malignant neoplasm of trophoblastic origin . The tumor is known for its association with molar pregnancy, its rapid hematogenous spread to multiple organs, high human chorionic gonadotropin levels, and its response to chemotherapy [4,13]. Metastases to the brain occur frequently [2,4,5,13] and are responsible for most of the deaths from this disease [3,14] . They occur as single or multiple lesions and usually produce symptoms of multiple strokes or subarachnoid hemorrhage . Metastases to the small intestine, liver, and spleen have been reported [30] . In this report, we describe a case of ruptured oncotic cerebral aneurysm from metastatic choriocarcinoma, complicated by spontaneous splenic rupture.
Address reprint requests to : Somnath Nair, M .D ., Department of Neurosurgery, Hahnemann University, Broad and Vine, Philadelphia,
PA 19102-1192 . Received August 23, 1991 ;
accepted February
J 1992 by Elsevier Science Publishing Co . . Inc
13, 1992 .
Case Report A 30-year-old woman with a 10-day history of severe, intermittent headache, nausea, and vomiting was taken to a local hospital after being found unconscious . Past medical history was significant for metrorrhagia 2 weeks prior to admission . She had had two uncomplicated pregnancies 6 years and 2 years previously . On examination, she was lethargic but arousable and had severe left hemiparesis . Computed tomographic (CT) scan of the head revealed a large right temporoparietal hemorrhage, with diffuse subarachnoid blood and shift of mass effect right to left (Figure 1) . Routine hematological, serum electrolyte, and liver function studies were within normal limits ; chest radiograph showed a right lower lobe density . The patient was transferred the next day to Hahnemann University Hospital, where cerebral angiography demonstrated a distal right middle cerebral artery (MCA) aneurysm with a suspected focus of rupture . There was considerable vasospasm of multiple cerebral branches (Figures 2 and 3) . Three days after the initial episode, a right temporoparietal craniotomy was performed . After the dura was opened, the brain was noted to be hyperemic, with bulging of the precentral gyrus . The intracerebral hematoma was removed through a small cortical incision . No tumor tissue was seen in the clot . A saccular aneurysm was visible in the depths and slightly anterior to the hematoma . Subarachnoid dissection exposed a deep feeding and a superficial draining portion of the tense aneurysm . A medium-length curved Yasargil clip was placed across the neck of the aneurysm . Postoperatively, the patient was responsive to simple commands and showed return of some movement to her left lower extremity . CT scan immediately after surgery showed significant decrease of the intracerebral hematoma and the mass effect. On postoperative day 1, she became acutely hypotensive ; the abdomen was distended and hemoglobin dropped to 1 .5 g/dL . Culdocentesis revealed hemoperitoneum . Urine was positive for 0090-3019/92/S5.00
Choriocarcinoma and intracranial aneurysm
Surg Neurol 1992 ; 3 8 :236-40
237
Figure 1 . CT of head showing right temporoparietal henurtoma with diffuse suharachnoid bleeding and shift of mass effect right to left,
Figure 3. Cerebral angiogram (anterior-posterior vieut) of right carotid
human chorionic gonadotropin (/3-HCG) . She was resuscitated with intravenous fluids and blood products, and an exploratory laparotomy was performed for suspected ectopic pregnancy . There was no evidence of extrauterine pregnancy, and the uterus and adnexae were normal . The spleen had a large subcapsular hematoma that had ruptured freely into the abdomen . A splenectomy was performed . The rest of the abdomen was free of any active bleeding . Postoperatively, the patient was hemodynamically stable, but responded to deep pain only . Serial serum /3-HCG levels ranged from 12,700 mlU/mL (normal value < 4 mIU/mL in males and nonpregnant females) on the day of laparotomy to 46,700 mlU/mL on subsequent days . Pelvic ultrasound was negative for intrauterine pregnancy . Dilation and curettage were considered for treatment of suspected trophoblastic disease but were not carried out due to the patient's precarious
clinical status . CT scan of the head at this time showed a large hemispheric infarction with edema and worsening herniation on the right side . Despite aggressive medical therapy, which included induced barbiturate coma, the patient's condition continued to deteriorate, and she died 2 weeks following admission . Autopsy disclosed metastasis from choriocarcinoma to the middle and lower lobes of the right lung and to both kidneys . Brain metastases were found within the necrotic vessel wall of the aneurysm, and nests of tumor cells were seen in the surrounding hematoma (Figure 4) . The spleen, liver, mediastinum, uterus, cervix, vagina, and adnexae were free of tumor .
Figure 2 . Cerebral angiogram (lateral view) of right carotid artery showing distal right MCA aneurysm .
artery showing distal right middle cerebral artery aneurysm .
Discussion Gestational choriocarcinoma (GCC) is a rare, highly malignant tumor, occurring in one of 20,000 to 40,000 pregnancies in the United States [5,14] . Significantly higher incidences are reported in Southeast Asia and Taiwan [14] . Choriocarcinoma is the most malignant of a spectrum of disorders of the trophoblast, the most benign of which is the hydatidiform mole . Fifty percent of gestational choriocarcinomas arise from molar pregnancies, 25% are subsequent to abortion, 23% follow normal pregnancy, and 3% are subsequent to ectopic pregnancy [10,13] . GCC is typically diagnosed within months of an antecedent pregnancy [14] ; however, periods ranging from 2 days to 17 years have been found to intervene between pregnancy and diagnosis [4,9,12,14] . GCC is known for its propensity for rapid hematogenous spread to the lungs (94% of metastatic GCC), followed by vagina (44%), brain (28%), liver (28%), kidney (25%), and ovaries (22%) [30} . Patients usually present with vaginal bleeding after pregnancy ; however, gastro-
238
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Giannakopoulos et al
Figure 4. Histological section of tumor tissue in and around aneurysm wall, showing rare syncyliotrophoblastic giant yells (arrow) (hematoxylin and eosin, original magne cation X250) .
intestinal, respiratory, genitourinary, or central nervous system manifestations account for one third of presentations [13] . As in the case presented here, many patients with choriocarcinoma have no evidence of a primary malignancy at the time of diagnosis or at autopsy [1] . These cases probably represent GCC . Cerebral metastases develop in 20%-30% of patients with GCC [13,16,20,21,30] ; however, cerebral metastases are responsible for 50% of deaths due to this disease L31 . Many studies have shown that 95%-99% of patients with brain metastases from GCC also have pulmonary metastases, and it is likely that pulmonary lesions are the usual source of brain metastases [1,10] . The mechanism of tumor spread is believed to be one of arterial embolization and the inherent ability of the trophoblast to invade vessels in an end-arterial system . Hypothetical mechanisms for bleeding from intracranial neoplasm have been proposed as follows : (1) rupture of immature vessels due to venous congestions secondary to elevated intracranial pressure, (2) hemorrhagic necrosis caused by the compression effect of the neoplasm, and (3) direct invasion of the rapidly growing tumor into the vascular wall . The majority of previous reports support the last concept as the most probable cause of massive hemorrhage . It is likely that after tumor embolization in the distal cerebral vessels, there is focal destruction of the intima, internal elastic lamina, and media layers, with true aneurysm formation . Other mechanisms include lodging of the tumor embolus in the vasa vasorum, involvement of the internal elastic lamina, and
aneurysmal formation in the final stage. Such mechanisms are similar to the explanation given for the growth of mycotic aneurysms [261 . More than half of single metastases are found in the cerebral hemispheres posterior to the rolandic fissure, particularly the terminal distribution of the MCA [10] . Metastases are seen in decreasing order of frequency from the parietal to the temporal to the frontal lobes . Patients with central nervous system involvement from GCC may present with an acute stroke or encephalitic syndrome . Intracranial hemorrhage is the most frequent mode of presentation of cerebral involvement and accounts for two thirds of the cerebral metastases [10] . The intracranial hemorrhage may be subdural, subarachnoid, or intracerebral . The most common symptoms are headache, nausea, vomiting, hemiparesis, altered mental status, and seizures . Neurological symptoms may resemble transient ischemic attacks, suggesting tumor embolization [22] . On CT scan of the head, a tumor nodule may be seen as a high-density, contrast-enhancing lesion with surrounding edema or as an isolated intracranial hemorrhage . In patients with no known history of molar pregnancy presenting with intracranial hemorrhage, the diagnosis is made by obtaining a serum /3-HCG titer . Peripherally located aneurysms in the brain are seldom congenital or atherosclerotic in origin . They are usually secondary to infection, neoplasm, trauma, or Moyamoya disease, or are idiopathic [20] . Neoplastic aneurysms are rare [ 15] and, when they occur, are generally associated with embolization from cardiac myxoma .
Surg Neurol 1992 ;38 ;236- 4 0
Choriocarcinoma and intracranial aneurysm
Table 1 . Reported Cases of I ntracranial Aneurysm from Metastatic Choriocarcinoma Location of Source Age, yr Presentation aneurysm Case 1 2 3
4 5
6 8
9 10 11 12 13
14, 15 16 17 18
Montaut et al [17] Montaut et al [17] Montaut et al [17] Stilp et al [25] Shuangshoti et al [24] Nakahara et al [18] Olmstead & McGee [20] Weir et al [30] Weed & Hammond [29] Pullar et al [21] Momma et al [16] Toyama et al [26] Seigle et at [22] Hisanaga et al [8]a (2 cases) Noterman cc al [19] Fujiwara et al [7] Present report
Incracerebral hematoma
21 18 21 22 40 22 16 25 20 16 29 20 28
SAH SAH Hemiplegia Hemiparesis Hemiparesis SAH Aphasia, hemiplegia Hemiplegia SAH Vaginal bleed SAH Hemiparesis SAH
R MCA
+
L MCA (2) L MCA R MCA L MCA R MCA, R callosomarginal R MCA L MCA R MCA L MCA R MCA R MCA R MCA (2), L MCA (2)
+
30 26 30
Hemiplegia Hemiparesis Hemiplegia, SAH
R MCA L MCA (3) R MCA
+
+ + + + + + + +
239
Outcome Died (1 month) Died (1 month) Died (4 months) Good (4 years) Lost to follow-up Good (3 years) Died Died Died (3 years) Good (12 months) Died (1 month) Good (6 months) Died Died (23 months) Good (6 years) Died (2 weeks)
Abbreviations : SAH, suhararhnoid hemorrhage ; R, right ; MCA, middle cerebral artery. L, left . "Japanese literature .
Review of the literature revealed 17 reported cases of oncotic cerebral aneurysms from metastatic GCC (Table 1) . Our patient represents the 18th case . Of the previous 17 cases, most aneurysms were single and located on one of the terminal branches of the MCA, similar to the aneurysm in our case . One patient had an aneurysm of the right MCA and concurrently one of the right callosomarginal artery . Another case demonstrated four aneurysms, two of the right MCA and two of the left posterior cerebral artery . However, these multiple and bilateral aneurysms were attributable to an embolic focus from metastatic GCC to the left ventricle of the heart [22] . Sudden intraperitoneal hemorrhage in women of child-bearing age, apart from trauma, is most commonly associated with ruptured ectopic pregnancy . Less common causes of abdominal apoplexy include ruptured corpus luteum cysts, hepatic adenomas, and spontaneous splenic rupture . Hemoperitoneum secondary to rupture of splenic metastases of GCC has been reported [11,30] . The patients with splenic rupture were managed by splenectomy or by angiographic embolization [27] . In the present case, no tumor was identified in the spleen . The explanation may be hemorrhage and necrosis of small tumor foci, and possible removal of tumor cells with evacuation of the hemoperitoneum . Our case represents the first report of oncotic cerebral aneurysm from metastatic GCC associated with spontaneous splenic rupture . Failure to find GCC in the reproductive organs, specifically the uterus, may be related to the patient's metrorrhagia 2 weeks prior to admission, possibly representing hemorrhage and necrosis of uterine tumor .
Patients with choriocarcinoma may be divided into good and poor prognosis groups, the latter associated with the presence of malignant disease for 4 months, occurrence after term gestation, serum /3-HCG 40,000 mIU/mL or urine /3-HCG 100,000 IU/24 h (normal value < 10 IU/24 h in males and nonpregnant females), presence of liver or brain metastases, and failure to respond to previous chemotherapy . Patients with a "good prognosis" have potential cure rates of 100% with single-agent chemotherapy using methotrexate or actinomycin D [4,13] . Recent studies have demonstrated cure rates of 60%-90% for "poor prognosis" patients, using multidrug regimens, irradiation, and surgery in selective cases [4,6,9,22,29] . Surgery is generally limited to life-threatening situations such as abdominal or intracranial bleeding and to selective resection of accessible metastases [1,4,23,28] . Despite such improvements, the mortality for patients with cerebral metastases remains high [29] . Most patients succumb within the first 15 days of diagnosis, either due to intracranial bleeding before treatment or as a complication of therapy [20,23] . The presentation of intracranial hemorrhage with nongestational choriocarcinoma is rare . The diagnosis should be considered in women of child-hearing age who present with subarachnoid or intracerebral hemorrhage, especially if there is evidence of metastatic disease elsewhere . The diagnosis can be confirmed by a high serum /3-HCG level . Because the prognosis is excellent with combined chemotherapy and radiation therapy, early recognition of this rare disease is of critical importance .
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Surg Neurol 1992 ; 3 8 :236-40
The editorial assistance of Perry Black, M .D ., and Mary F . Boylan, M .A ., in the prepararion of the manuscript is gratefully acknowledged .
References 1. Athanassiou
A, Begent RH, Newlands ES, Parker D, Rustin GJ, Bagshawe KD . Central nervous system metastases of choriocarcinoma. 23 years experience at Charing Cross Hospital . Cancer 1983 ;52 :1728-35 . 2 . Berkowitz RS, Goldstein DP, Bernstein MR . Choriocarcinoma following term gestation . Gynecol Oncol 1984 ;17 :52-7 . 3 . Biller J, Adams HP . Cerebrovascular disorders associated with pregnancy . Am Fm Physician 1985 ;33 :125-32 . 4 . Blauscein A. Pathology of the female genital tract, 2nd ed . New York: Springer-Verlag, 1982 :791-803 . 5 . Burrow GN, Ferris TF. Medical complications during pregnancy, 3rd ed . Philadelphia : W.B. Saunders, 1988 :548-50 . 6 . Erb RE, Giblet WB . Massive hemoperitoneum following rupture of hepatic metastases from unsuspected choriocarcinoma . Am J Emerg Med 1989 ;7 :196-8 . . 7 Fujiwara T, Mino S, Nagao S, Ohmoto, T . Metauatic choriocarcinoma with neoplastic aneurysms cured by aneurysm resection and chemotherapy . J Neurosurg 1992 ;76 :148-51 .
8 . Hisanaga M, Kawai S, Maekawa M, Hattori Y, Kotoh K . Neoplastic aneurysms due to cerebral metastasis of choriocarcinoma . Report of two cases . Neuro Med Chir (Tokyo) 1988 ;28 :398-403 (in Japanese) . 9 . Ilancheran A, Ramam SS, Baratham G. Metastaric cerebral choriocarcinoma with primary neurologic presentation . Gynecol Oncol 1988 ;29 :361-4 . 10 . Ishizuka T, Tomoda Y, Kaseki S, Goto S, Hara T, Kobayashi T . Intracranial metastasis of choriocarcinoma: a clinicopathologic study . Cancer 1983 ;52 :1895-903 . 11 . Kristifferson A, Edmin S, Jarhult J . Acute intestinal obstruction and splenic hemorrhage due to metastatic choriocarcinoma . Acra Chic Scand 1985 ;15L381-4 . 12 . Kumar 3, Ilancheran A, Ratnam SS. Pulmonary metastases in gestational trophoblastic disease : a review of 97 cases . Br J Obstet Gynaecol 1988 ;95 :70-4 . 13 . Mates SM, Yetsko RA. Metastatic gestational choriocarcinoma : two cases. Ann Emerg Med 1988 ;17 :540-2 . . 14 McDonald TW, Ruffolo EH . Modern management of gestational trophoblastic disease . Obstet Gynecol Surg 1983 ;38 :67-83 .
Giannakopoulos et al
15 . Merritt HH . A textbook of neurology, 3rd ed . Philadelphia: Lea & Febiget, 1983 :301-5 . 16. Momma F, Beck H, Miyamoto T, Nagao S . Intracranial aneurysm due to metastatic choriocarcinoma . Surg Neurol 1986;25 :74-6 . 17 . Montaut J, Hepner H, Tridon P, Picard L, Floquet J, Lepoire J . Aspects pseudovasculaires des metastases intracraniennes des chorioepitheliomes . Neurochirurgie 1971 ;17 :119-28 . 18 . NakaharaT,NonakaN,KinoshitaK,MatsukadoY .Subarachnoid hemorrhage and aneurysmal change of cerebral arteries due to metastases of chorioepithelioma. No Shinkei Geka 1975 ;3 : 777-82 (in Japanese). 19 . Noterman J, Verhest A, Baleriaux D, Brotchi J . A ruptured cerebral aneurysm from choriocarcinomatous origin . A case report and a review . Neurosurg Rev 1989;12 :71-4 . 20 . Olmsted WW, McGee TP . The pathogenesis of peripheral aneurysms of the central nervous system : a subject review of the AFIP . Radiology 1977 ;123:661-6. 21 . Pullar M, Blumbergs PC, Phillips GE, Carney PG . Neoplastic cerebral aneurysm from metastatic gestational choriocarcinoma : case report. J Neurosurg 1985 ;63 :644-7 . 22 . Seigle JM, Caputy MD, Manz HJ, Wheeler C, Fox JL . Multiple oncotic tntracranial aneurysms and cardiac metastases from choriocarcinoma : case report and review of the literature . Neurosurgery 1987 ;20 :39-42 . 23 . Sen DK, Sivanesaratnum V, Chuah CY, Ch'ng SL, Singh J, Paramsothy M. Cerebral metasrases from choriocarcinoma : results of chemotherapy . Acta Obstet Gynecol Scand 1987 ;66 :425-8 . 24 . Shuangshoti S, Panyathanya R, Wichienkur P . larracranial metastases from unsuspected choriocarcinoma . Onset suggestive of cerebrovascular disease . Neurology 1974 ;24 :649-54 . 25 . StilpTJ,BucyPC,BrewerJl .Cure ofmetastaticchoriorcarcinoma of the brain . JAMA 1972 ;221 :276-9 . 26. Toyama K, Tanaka T, Hirota T, Misu N, Mizuno K . A case report of neoplastic aneurysm due to metastatic choriocarcinoma. No Shinkei Geka 1986 ;14 :385-90 (in Japanese) . 27, Vujic I, Lutz MH, Curry N, Weinstein VJ . Angiographic management of bleeding in gestational rrphoblastic malignancy . Am J Obstet Gynecol 1984 ;149 :90-2 . 28. Vujic I, Stanley JH, Gobien RP, Bruce RJ, Lutz MH . Embolic management of rare hemorrhagic gynecologic and obstetrical conditions . Cardiovasc Intervent Radiol 1986 ;9 :69-74 . 29. Weed JC, Hammond CB . Cerebral metastatic choriocarcinoma: intensive therapy and prognosis . Obsret Gynecol 1980 ;55 :80-94 . . 30 Weir B, MacDonald N, Mielke B . Intracrantal vascular complications of choriocarcinoma. Neurosurgery 1978 ;2 :138-42 .
Surg Neurol 1992 ;38 :236-40
Implications for the Pathogenesis of Aneurysm Formation : Metastatic Choriocarcinoma with Spontaneous Splenic Rupture . Case Report and a Review George Giannakopoulos, M .D., Somnath Nair, M .D., Cameron Snider, and Peter S . Amenta, M.D., Ph.D. Departments of Neurosurgery and Pathology, Hahnemann University, Philadelphia, Pennsylvania
Giannakopoulos G, Nair S, Snider C, Amenta PS . Implications for the pathogenesis of aneurysm formation : metastatic choriocarcinoma with spontaneous splenic rupture . Case report and a review. Surg Neurol 1992 ;38 :236-40 . We report a case of ruptured intracranial aneurysm from metastatic choriocarcinoma in a patient presenting with intracerebral hemorrhage . Operative evacuation of the hematoma with clipping of a distal right middle cerebral artery aneurysm was performed . Postoperatively, the patient developed hypovolemic shock from spontaneous splenic rupture. Histopathologic examination of the cerebral aneurysm showed choriocarcinoma invading the vessel wall . Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral or subarachnoid hemorrhage in women of child-bearing age . KEY
WORDS :
IntraCranial
aneurysm ; Choriocarcinoma ;
Splenic rupture
Choriocarcinoma is a rare, highly malignant neoplasm of trophoblastic origin . The tumor is known for its association with molar pregnancy, its rapid hematogenous spread to multiple organs, high human chorionic gonadotropin levels, and its response to chemotherapy [4,13]. Metastases to the brain occur frequently [2,4,5,13] and are responsible for most of the deaths from this disease [3,14] . They occur as single or multiple lesions and usually produce symptoms of multiple strokes or subarachnoid hemorrhage . Metastases to the small intestine, liver, and spleen have been reported [30] . In this report, we describe a case of ruptured oncotic cerebral aneurysm from metastatic choriocarcinoma, complicated by spontaneous splenic rupture.
Address reprint requests to : Somnath Nair, M .D ., Department of Neurosurgery, Hahnemann University, Broad and Vine, Philadelphia,
PA 19102-1192 . Received August 23, 1991 ;
accepted February
J 1992 by Elsevier Science Publishing Co . . Inc
13, 1992 .
Case Report A 30-year-old woman with a 10-day history of severe, intermittent headache, nausea, and vomiting was taken to a local hospital after being found unconscious . Past medical history was significant for metrorrhagia 2 weeks prior to admission . She had had two uncomplicated pregnancies 6 years and 2 years previously . On examination, she was lethargic but arousable and had severe left hemiparesis . Computed tomographic (CT) scan of the head revealed a large right temporoparietal hemorrhage, with diffuse subarachnoid blood and shift of mass effect right to left (Figure 1) . Routine hematological, serum electrolyte, and liver function studies were within normal limits ; chest radiograph showed a right lower lobe density . The patient was transferred the next day to Hahnemann University Hospital, where cerebral angiography demonstrated a distal right middle cerebral artery (MCA) aneurysm with a suspected focus of rupture . There was considerable vasospasm of multiple cerebral branches (Figures 2 and 3) . Three days after the initial episode, a right temporoparietal craniotomy was performed . After the dura was opened, the brain was noted to be hyperemic, with bulging of the precentral gyrus . The intracerebral hematoma was removed through a small cortical incision . No tumor tissue was seen in the clot . A saccular aneurysm was visible in the depths and slightly anterior to the hematoma . Subarachnoid dissection exposed a deep feeding and a superficial draining portion of the tense aneurysm . A medium-length curved Yasargil clip was placed across the neck of the aneurysm . Postoperatively, the patient was responsive to simple commands and showed return of some movement to her left lower extremity . CT scan immediately after surgery showed significant decrease of the intracerebral hematoma and the mass effect. On postoperative day 1, she became acutely hypotensive ; the abdomen was distended and hemoglobin dropped to 1 .5 g/dL . Culdocentesis revealed hemoperitoneum . Urine was positive for 0090-3019/92/S5.00
Choriocarcinoma and intracranial aneurysm
Surg Neurol 1992 ; 3 8 :236-40
237
Figure 1 . CT of head showing right temporoparietal henurtoma with diffuse suharachnoid bleeding and shift of mass effect right to left,
Figure 3. Cerebral angiogram (anterior-posterior vieut) of right carotid
human chorionic gonadotropin (/3-HCG) . She was resuscitated with intravenous fluids and blood products, and an exploratory laparotomy was performed for suspected ectopic pregnancy . There was no evidence of extrauterine pregnancy, and the uterus and adnexae were normal . The spleen had a large subcapsular hematoma that had ruptured freely into the abdomen . A splenectomy was performed . The rest of the abdomen was free of any active bleeding . Postoperatively, the patient was hemodynamically stable, but responded to deep pain only . Serial serum /3-HCG levels ranged from 12,700 mlU/mL (normal value < 4 mIU/mL in males and nonpregnant females) on the day of laparotomy to 46,700 mlU/mL on subsequent days . Pelvic ultrasound was negative for intrauterine pregnancy . Dilation and curettage were considered for treatment of suspected trophoblastic disease but were not carried out due to the patient's precarious
clinical status . CT scan of the head at this time showed a large hemispheric infarction with edema and worsening herniation on the right side . Despite aggressive medical therapy, which included induced barbiturate coma, the patient's condition continued to deteriorate, and she died 2 weeks following admission . Autopsy disclosed metastasis from choriocarcinoma to the middle and lower lobes of the right lung and to both kidneys . Brain metastases were found within the necrotic vessel wall of the aneurysm, and nests of tumor cells were seen in the surrounding hematoma (Figure 4) . The spleen, liver, mediastinum, uterus, cervix, vagina, and adnexae were free of tumor .
Figure 2 . Cerebral angiogram (lateral view) of right carotid artery showing distal right MCA aneurysm .
artery showing distal right middle cerebral artery aneurysm .
Discussion Gestational choriocarcinoma (GCC) is a rare, highly malignant tumor, occurring in one of 20,000 to 40,000 pregnancies in the United States [5,14] . Significantly higher incidences are reported in Southeast Asia and Taiwan [14] . Choriocarcinoma is the most malignant of a spectrum of disorders of the trophoblast, the most benign of which is the hydatidiform mole . Fifty percent of gestational choriocarcinomas arise from molar pregnancies, 25% are subsequent to abortion, 23% follow normal pregnancy, and 3% are subsequent to ectopic pregnancy [10,13] . GCC is typically diagnosed within months of an antecedent pregnancy [14] ; however, periods ranging from 2 days to 17 years have been found to intervene between pregnancy and diagnosis [4,9,12,14] . GCC is known for its propensity for rapid hematogenous spread to the lungs (94% of metastatic GCC), followed by vagina (44%), brain (28%), liver (28%), kidney (25%), and ovaries (22%) [30} . Patients usually present with vaginal bleeding after pregnancy ; however, gastro-
238
Surg Neurol 1992 ;38 :236-40
Giannakopoulos et al
Figure 4. Histological section of tumor tissue in and around aneurysm wall, showing rare syncyliotrophoblastic giant yells (arrow) (hematoxylin and eosin, original magne cation X250) .
intestinal, respiratory, genitourinary, or central nervous system manifestations account for one third of presentations [13] . As in the case presented here, many patients with choriocarcinoma have no evidence of a primary malignancy at the time of diagnosis or at autopsy [1] . These cases probably represent GCC . Cerebral metastases develop in 20%-30% of patients with GCC [13,16,20,21,30] ; however, cerebral metastases are responsible for 50% of deaths due to this disease L31 . Many studies have shown that 95%-99% of patients with brain metastases from GCC also have pulmonary metastases, and it is likely that pulmonary lesions are the usual source of brain metastases [1,10] . The mechanism of tumor spread is believed to be one of arterial embolization and the inherent ability of the trophoblast to invade vessels in an end-arterial system . Hypothetical mechanisms for bleeding from intracranial neoplasm have been proposed as follows : (1) rupture of immature vessels due to venous congestions secondary to elevated intracranial pressure, (2) hemorrhagic necrosis caused by the compression effect of the neoplasm, and (3) direct invasion of the rapidly growing tumor into the vascular wall . The majority of previous reports support the last concept as the most probable cause of massive hemorrhage . It is likely that after tumor embolization in the distal cerebral vessels, there is focal destruction of the intima, internal elastic lamina, and media layers, with true aneurysm formation . Other mechanisms include lodging of the tumor embolus in the vasa vasorum, involvement of the internal elastic lamina, and
aneurysmal formation in the final stage. Such mechanisms are similar to the explanation given for the growth of mycotic aneurysms [261 . More than half of single metastases are found in the cerebral hemispheres posterior to the rolandic fissure, particularly the terminal distribution of the MCA [10] . Metastases are seen in decreasing order of frequency from the parietal to the temporal to the frontal lobes . Patients with central nervous system involvement from GCC may present with an acute stroke or encephalitic syndrome . Intracranial hemorrhage is the most frequent mode of presentation of cerebral involvement and accounts for two thirds of the cerebral metastases [10] . The intracranial hemorrhage may be subdural, subarachnoid, or intracerebral . The most common symptoms are headache, nausea, vomiting, hemiparesis, altered mental status, and seizures . Neurological symptoms may resemble transient ischemic attacks, suggesting tumor embolization [22] . On CT scan of the head, a tumor nodule may be seen as a high-density, contrast-enhancing lesion with surrounding edema or as an isolated intracranial hemorrhage . In patients with no known history of molar pregnancy presenting with intracranial hemorrhage, the diagnosis is made by obtaining a serum /3-HCG titer . Peripherally located aneurysms in the brain are seldom congenital or atherosclerotic in origin . They are usually secondary to infection, neoplasm, trauma, or Moyamoya disease, or are idiopathic [20] . Neoplastic aneurysms are rare [ 15] and, when they occur, are generally associated with embolization from cardiac myxoma .
Surg Neurol 1992 ;38 ;236- 4 0
Choriocarcinoma and intracranial aneurysm
Table 1 . Reported Cases of I ntracranial Aneurysm from Metastatic Choriocarcinoma Location of Source Age, yr Presentation aneurysm Case 1 2 3
4 5
6 8
9 10 11 12 13
14, 15 16 17 18
Montaut et al [17] Montaut et al [17] Montaut et al [17] Stilp et al [25] Shuangshoti et al [24] Nakahara et al [18] Olmstead & McGee [20] Weir et al [30] Weed & Hammond [29] Pullar et al [21] Momma et al [16] Toyama et al [26] Seigle et at [22] Hisanaga et al [8]a (2 cases) Noterman cc al [19] Fujiwara et al [7] Present report
Incracerebral hematoma
21 18 21 22 40 22 16 25 20 16 29 20 28
SAH SAH Hemiplegia Hemiparesis Hemiparesis SAH Aphasia, hemiplegia Hemiplegia SAH Vaginal bleed SAH Hemiparesis SAH
R MCA
+
L MCA (2) L MCA R MCA L MCA R MCA, R callosomarginal R MCA L MCA R MCA L MCA R MCA R MCA R MCA (2), L MCA (2)
+
30 26 30
Hemiplegia Hemiparesis Hemiplegia, SAH
R MCA L MCA (3) R MCA
+
+ + + + + + + +
239
Outcome Died (1 month) Died (1 month) Died (4 months) Good (4 years) Lost to follow-up Good (3 years) Died Died Died (3 years) Good (12 months) Died (1 month) Good (6 months) Died Died (23 months) Good (6 years) Died (2 weeks)
Abbreviations : SAH, suhararhnoid hemorrhage ; R, right ; MCA, middle cerebral artery. L, left . "Japanese literature .
Review of the literature revealed 17 reported cases of oncotic cerebral aneurysms from metastatic GCC (Table 1) . Our patient represents the 18th case . Of the previous 17 cases, most aneurysms were single and located on one of the terminal branches of the MCA, similar to the aneurysm in our case . One patient had an aneurysm of the right MCA and concurrently one of the right callosomarginal artery . Another case demonstrated four aneurysms, two of the right MCA and two of the left posterior cerebral artery . However, these multiple and bilateral aneurysms were attributable to an embolic focus from metastatic GCC to the left ventricle of the heart [22] . Sudden intraperitoneal hemorrhage in women of child-bearing age, apart from trauma, is most commonly associated with ruptured ectopic pregnancy . Less common causes of abdominal apoplexy include ruptured corpus luteum cysts, hepatic adenomas, and spontaneous splenic rupture . Hemoperitoneum secondary to rupture of splenic metastases of GCC has been reported [11,30] . The patients with splenic rupture were managed by splenectomy or by angiographic embolization [27] . In the present case, no tumor was identified in the spleen . The explanation may be hemorrhage and necrosis of small tumor foci, and possible removal of tumor cells with evacuation of the hemoperitoneum . Our case represents the first report of oncotic cerebral aneurysm from metastatic GCC associated with spontaneous splenic rupture . Failure to find GCC in the reproductive organs, specifically the uterus, may be related to the patient's metrorrhagia 2 weeks prior to admission, possibly representing hemorrhage and necrosis of uterine tumor .
Patients with choriocarcinoma may be divided into good and poor prognosis groups, the latter associated with the presence of malignant disease for 4 months, occurrence after term gestation, serum /3-HCG 40,000 mIU/mL or urine /3-HCG 100,000 IU/24 h (normal value < 10 IU/24 h in males and nonpregnant females), presence of liver or brain metastases, and failure to respond to previous chemotherapy . Patients with a "good prognosis" have potential cure rates of 100% with single-agent chemotherapy using methotrexate or actinomycin D [4,13] . Recent studies have demonstrated cure rates of 60%-90% for "poor prognosis" patients, using multidrug regimens, irradiation, and surgery in selective cases [4,6,9,22,29] . Surgery is generally limited to life-threatening situations such as abdominal or intracranial bleeding and to selective resection of accessible metastases [1,4,23,28] . Despite such improvements, the mortality for patients with cerebral metastases remains high [29] . Most patients succumb within the first 15 days of diagnosis, either due to intracranial bleeding before treatment or as a complication of therapy [20,23] . The presentation of intracranial hemorrhage with nongestational choriocarcinoma is rare . The diagnosis should be considered in women of child-hearing age who present with subarachnoid or intracerebral hemorrhage, especially if there is evidence of metastatic disease elsewhere . The diagnosis can be confirmed by a high serum /3-HCG level . Because the prognosis is excellent with combined chemotherapy and radiation therapy, early recognition of this rare disease is of critical importance .
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Surg Neurol 1992 ; 3 8 :236-40
The editorial assistance of Perry Black, M .D ., and Mary F . Boylan, M .A ., in the prepararion of the manuscript is gratefully acknowledged .
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