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Decreasing Incidence of Sudden Death Due to Undiagnosed Primary Central Nervous System Tumors.

Although brain tumors are relatively uncommon neoplasms, they often result in death. Brain tumor incidence in the United States is estimated to be 12.8 per 100 000.[1] Mortality due to brain tumors is particularly significant in adults aged 20 to 39 years. Primary intracranial neoplasms represent the third leading cancer-related cause of death during these 2 decades.[1] The majority of deaths due to brain tumors are preceded by long periods of symptoms, resulting in diagnosis of the neoplasms. In some cases, however, the tumor is not identified or the patients do not seek health care. In this report, we focus on cases of unexpected death due to undiagnosed primary intracranial neoplasms.

We present 76 cases of primary CNS tumors identified at autopsy between January 1980 and December 1999 (inclusive) at the Office of the Chief Medical Examiner of the State of Maryland (Table 1). We concentrate in particular on 11 cases in which the CNS tumor was the cause of death or contributed significantly to the patient's death, but was not identified prior to the patient's demise.
Table 1. Primary Central Nervous System Neoplasms Identified in 54 873
Coroners' Autopsies (1980-1999)(*)

Case
No. Age, y/Sex/Race Site

 1 20/F/W Left frontal lobe
 2 36/M/B Thoracic spinal cord
 3 42/F/W Third ventricle
 4 24/F/W Pontocerebellar angle
 5 39/M/B Leftfrontal lobe
 6 29/F/W Septum pellucidum
 7 35/M/B Right basal ganglia
 8 29/F/A Left cerebrum
 9 39/M/W Left frontal lobe
10 78/M/B Pituitary/frontal lobes
11 45/M/W Right frontal lobe
12 49/M/W Brainstem/basal ganglia
13 46/M/W Parietal/brainstem
14 61/M/W Bilateral
15 43/M/W Basal ganglia
16 46/F/W CP angle/spinal cord
17 43/F/B Right cerebrum
18 36/M/B Right temporal lobe
19([dagger]) 47/F/B Left frontal/basal ganglia
 47/F/B Left frontal lobe
20 44/F/W Medulla
21 74/F/B Pituitary stalk
22 43/F/B Right fronto-orbital
23 7/M/W Right CP angle
24 15/F/W Corpus callosum
25 .../F/... Right cerebellum
26 75/M/B Right frontal lobe
27 35/M/B Right frontal lobe
28 23/M/W Cerebellum
29 35/M/B Left CP angle
30 48/M/B Falx
31 41/F/B Left sphenoid ridge
32 27/M/B Optic chiasm
33 .../M/... Right orbitofrontal
34 1/M/W Fourth ventricle
35 63/M/W Base of brain
36 43/F/W Left frontal lobe
37 52/M/B Right pons
38 .../F/B Optic chiasm
39 54/M/... Fornix
40 64/F/B Left frontal lobe
41 45/F/W Right parietal
42 42/M/B Pituitary
43 46/F/B Right frontal
44 70/F/W Left frontal lobe
45 84/F/W Left occipital
46 58/M/B Left brainstem
47 41/M/W Left parietal
48 49/F/W Right parietal
49 26/M/B Pituitary/optic chiasm
50 50/F/B Right frontal
51 38/M/B Right frontoparietal
52 27/F/W Right frontoparietal
53 42/F/W Pituitary
54 75/F/W Right occipital
55 77/F/W Falx
56 44/M/B Right caudate
57 43/M/W Right temporal
58 79/M/W CP angle
59 39/M/W Optic chiasm
60 22/M/W Clivus
61 34/F/W Base of brain
62 51/F/W Right frontal lobe
63 37/F/W Left frontal lobe
64 37/W/M Fourth ventricle
65 36/M/W Brainstem
66 .../M/... Right temporal lobe
67 .../M/... Pineal region
68 80/F/W Left frontal lobe
69 .../M/... Pituitary
70 .../M/... Pituitary region
71 11/F/A Left pons
72 84/F/W Right fronto-orbital
73 42/M/B Pituitary
74 .../M/... Right base
75 63/M/B Left frontal lobe
76 73/M/W Right parietal

 Cause
Case of Antemortem
No. Tumor Death Diagnosis

 1 Astrocytoma, grade II Y N
 2 Malignant glioma Y N
 3 Colloid cyst Y N
 4 Schwannoma Y N
 5 Glioblastoma multiforme Y N
 6 Colloid cyst Y N
 7 Glioblastoma multiforme Y N
 8 Glioblastoma multiforme Y N
 9 Malignant glioma Y N
10 Pituitary adenoma Y N
11 Glioblastoma multiforme Y N
12 Lymphoma Y Y
13 Glioblastoma multiforme Y Y
14 Glioblastoma multiforme Y Y
15 Lymphoma Y Y
16 Multiple schwannomas Y Y
17 Gemistocytic astrocytoma Y Y
18 Malignant glioma Y Y
19([dagger]) Astrocytoma, grade II Y U
 Meningioma ... U
20 Low-grade glioma U N
21 Meningioma U N
22 Meningioma U N
23 Dermoid cyst U N
24 Lipoma U Y
25 Hemangioblastoma U Y
26 Meningioma U Y
27 Low-grade glioma U Y
28 Pilocytic astrocytoma U U
29 Schwannoma U U
30 Malignant meningioma U U
31 Meningioma U U
32 Germinoma U U
33 Astrocytoma U U
34 Ependymoma U U
35 Meningioma U U
36 Transitional meningioma U U
37 Epidermoid U U
38 Epidermoid U U
39 Colloid cyst N N
40 Meningioma N N
41 Meningioma N N
42 Pituitary adenoma N N
43 Transitional meningioma N N
44 Meningioma N N
45 Meningioma N N
46 Epidermoid cyst N N
47 Meningioma N N
48 Meningioma N N
49 Dysgerminoma N N
50 Meningioma N N
51 Meningioma N N
52 Grade III glioma N Y
53 Pituitary adenoma N Y
54 Recurrent meningioma N Y
55 Meningioma N Y
56 Subependymoma N U
57 Epidermoid cyst N U
58 Schwannoma N U
59 Lipoma N U
60 Ecchordis physaliphora N U
61 Meningioma N U
62 Meningioma N U
63 Meningioma N U
64 Dermoid cyst N U
65 Glioma Grade II N U
66 Meningioma N U
67 Lipoma N U
68 Meningioma N U
69 Pituitary adenoma N U
70 Rathke's cleft cyst N U
71 Epidermoid cyst N U
72 Transitional meningioma N U
73 Granule cell tumor N U
74 Meningioma N U
75 Meningioma N U
76 Meningioma N U

(*) W indicates white; B, black; A, Asian; Y, yes; U, undetermined;
N, no.

([dagger]) An incidental meningioma was also identified in this patient.


The last large series reviewing sudden death due to undiagnosed primary CNS neoplasms was published by DiMaio and colleagues[2] 20 years ago. With the emergence of advanced neuroimaging and other improved diagnostic techniques, we thought it timely to reexamine cases of CNS tumors that eluded antemortem diagnosis but caused unexpected death. These cases highlight the continuing problem of death due to brain tumors that are undiagnosed or misdiagnosed because of vague symptoms, coexisting conditions, or poor access to health care.

METHODS

Neuropathology records of the Office of the Chief Medical Examiner of the State of Maryland were reviewed for the period January 1980 to December 1999 (inclusive), and all primary CNS tumor cases were identified. Autopsy findings, medical records, and histories taken by investigators at the time of death were reviewed to identify primary undiagnosed CNS tumors causing the individual's death. Cases in which the cause of death was known to be unrelated to neoplasia (trauma, drug overdose, cardiovascular disease, etc) were excluded. Also excluded were cases in which the tumor was only an incidental finding, such as a small meningioma unrelated to the individual's demise. Finally, we excluded cases in which medical records or other evidence demonstrated that the tumor had been identified previously. As in earlier studies, cases in which a tumor was thought to cause death directly by precipitating a motor vehicle accident were included. In many instances, sufficient data were not available to determine if an antemortem diagnosis had been made or if the tumor caused an individual's death. These cases are designated "undetermined" in Table 1.

REPORT OF CASES

Case 1

A 20-year-old woman was found dead in the bed of her college dormitory room at 4:30 PM. She was last seen alive at 1 AM on the same day. Her past medical history was unremarkable, except for a heart murmur

General autopsy was unremarkable, with no abnormalities identified in the heart. The brain weighed 1600 g and showed a cortical mass lesion in the left superior frontal gyrus, 4 cm behind the frontal pole. This lesion, which measured 4.0 x 2.5 cm at the surface of the brain, was soft and surrounded by edema. Cingulate herniation was not observed. At the base, there was questionable herniation of the left temporal lobe uncus. On coronal sections, the bulk of the lesion was located in the left frontal white matter with infiltration of the adjacent cerebral cortex. Neither hemorrhage nor necrosis was observed, and the ventricular system was normal. The brain stem, cerebellum, and hippocampal formations were normal. Microscopic examination revealed a grade II astrocytoma with infiltration of the cerebral cortex (Figure, E).

[ILLUSTRATION OMITTED]

In conclusion, this woman died as a consequence of a left frontal lobe astrocytoma, but the mechanism of death was uncertain. Possibilities included uncal herniation and seizure due to infiltration of the cerebral cortex by the tumor.

Case 2

Three weeks prior to death, a 36-year-old male wallpaper hanger developed a feeling of pressure, heaviness, and numbness in his right leg. He later developed low back pain, which radiated up to the back of the neck. He developed severe headaches associated with diplopia and blurred vision in the left eye. Balance was also impaired. A computed tomographic scan of the brain was conducted at a local emergency room and was unremarkable. The patient was then referred for neurosurgical consultation.

Upon clinical examination, the patient could not rotate his head to the left. He had questionable weakness of the right triceps muscle. The patient walked with a normal gait, and there was no tenderness on percussion of the lumbar spine. Hyperreflexia was noted in the lower extremities, with sustained ankle clonus on the right and bilateral Babinski signs. Sensation was normal in both lower extremities. The patient was scheduled for magnetic resonance imaging of the entire spine, but died prior to the imaging.

At autopsy, the brain weighed 1600 g. Gross inspection of the brain revealed no abnormalities. The spinal cord showed no external abnormality, but horizontal sections revealed softening and loss of anatomical landmarks in the lower segments of the thoracic region. No abnormality was noted in the cervical or lumbosacral cord. Microscopic sections confirmed the presence of an anaplastic astrocytoma centered in the thoracic and lumbar spinal cord, extending into the cervical cord and medulla (Figure, D). Death most likely resulted from tumor infiltration into the brainstem.

Case 3

A 42-year-old woman was found unresponsive in bed. Prior to her death, she apparently had not been feeling well due to stress. She had also complained about stomach and chest pains.

At autopsy, the general examination was unremarkable and revealed no evidence of trauma. The brain weighed 1330 g, and macroscopic examination revealed marked grooving of both temporal lobe unci. The cerebellar tonsils were not herniated or grooved. On coronal sections, the cerebral hemispheres demonstrated widespread, marked flattening of the gyri and marked dilation of the lateral ventricles. A spherical mass with a maximal diameter of 1.5 cm was present within the anterior third ventricle at the level of the foramen of Monro. In the midbrain, the aqueduct of Sylvius was slitlike. Microscopic sections from the third ventricle mass were diagnostic of a colloid cyst. In this case, death can be attributed to obstructive hydrocephalus and increased intracranial pressure.

Case 4

Two days prior to death, a 24-year-old, mentally handicapped, pregnant woman, who resided in a foster home, fell in the bathtub and hit her head. She went to a local emergency room, where she was examined and sent home with a diagnosis of neck strain. On the following day, she returned to the emergency room complaining of a headache and vomiting and was admitted to the obstetrics floor One day after admission, she suffered cardiovascular arrest and could not be resuscitated. The baby, who was in the third trimester of gestation, was delivered by cesarean section.

General autopsy was remarkable for evidence of a recent cesarean section. The brain weighed 1210 g and showed a large tumor measuring 4 x 3 cm in the left pontocerebellar angle. The tumor had a soft consistency and appeared cystic in one of its extremes; it indented the inferior surface of the left cerebellar hemisphere and displaced the medulla toward the contralateral side. The left cerebellar tonsil was displaced backward, and the right cerebellar tonsil was herniated and closely apposed to the medulla. Coronal sectioning of the brain revealed mild enlargement of the lateral and third ventricles and the aqueduct of Sylvius. Microscopic examination revealed a schwannoma (Figure, F). Death in this individual can be explained by tonsillar herniation, and distortion and compression of the medulla by the tumor.

Case 5

A 39-year-old man was found unresponsive on the bathroom floor by his landlord and was pronounced dead at the scene by paramedics. The decedent was last seen alive several days prior to his death, and his sister stated that he had recently been complaining of back pain.

At autopsy, the general examination was unremarkable and revealed no evidence of trauma. The brain weighed 1620 g, and macroscopic examination revealed congested leptomeninges covering the cerebral hemispheres. A 2 x 2-cm defect with extruding hemorrhage was noted in the left frontal pole. Left cingulate and uncal herniations were observed. On coronal sections, the cerebral hemispheres were asymmetrical with deviation of midline structures from left toward right. A massive fresh hemorrhage measuring 5.0 x 5.0 x 2.5 cm was noted in the left frontal white matter; it was surrounded by significant edema and focal necrosis, and extended into the subarachnoid space of the frontal pole. The hemorrhage also extended into the genu of the corpus callosum and the head of the left caudate nucleus. As a consequence of mass effect, central herniation was observed, in addition to the left cingulate and left uncal herniations, and the left lateral ventricle was partially collapsed. Microscopic sections revealed a glioblastoma multiforme. Massive hemorrhage into the glioblastoma, brain edema, and herniation explain the death of this patient.

Case 6

A 29-year-old woman was found unresponsive in the bathroom at 6:45 AM. On the previous night at 11 PM, she complained of a headache and vomited. Her past medical history was significant for migraine headaches treated with amitriptyline hydrochloride.

General autopsy was unremarkable. The brain weighed 1380 g and showed diffusely swollen cerebral hemispheres with marked flattening of the gyri throughout the convexities. At the base, the temporal lobe unci and hypothalamus were prominent, but definite herniation was not observed. The cerebellar tonsils were also prominent, without definite herniation. On coronal sections, the ventricular system was enlarged. A spherical mass, measuring 2.5 cm in diameter, was attached to the left side of the septum pellucidum at the level of the foramina of Monro (Figure, B). This spherical mass partially occupied the third and left lateral ventricles. Microscopic examination revealed a colloid cyst. The cause of death can be attributed to obstructive hydrocephalus and increased intracranial pressure secondary to intraventricular tumor.

Case 7

A 35-year-old man was found unresponsive at home and pronounced dead on the scene. He had recently complained of headache and neck pain. His past medical history was unremarkable except for a history of intravenous drug abuse.

At autopsy, external examination revealed needle tracks on the arms. There was no evidence of trauma. Toxicology tests for drugs and alcohol were negative. The brain weighed 1600 g and showed edema of the right cerebral hemisphere. There was right cingulate herniation, but no uncal or tonsillar herniation. On coronal sections, the right cerebral hemisphere showed a large mass lesion, which measured 5 x 4 cm in cross-section, involving the basal ganglia and internal capsule (Figure, A). This lesion was hemorrhagic and surrounded by edematous tissue with greenish discoloration. As a consequence of mass effect, the right lateral ventricle was completely collapsed, and the midline structures, including the third ventricle, were displaced from right to left. Microscopic examination revealed a glioblastoma multiforme. Mass effect from the tumor and increased intracranial pressure can explain the sudden death in this case.

Case 8

A 29-year-old Indonesian woman was found dead on the bathroom floor of the home where she had worked as a nanny for the past 7 years. She had recently complained of headaches and suffered episodes of vomiting. Her past medical history was unremarkable.

General autopsy was remarkable for acute pancreatitis. Coronal sections of the brain revealed a large frontoparietal mass. This mass, which had a volume of at least 250 mL, occupied most of the white matter of the left cerebral hemisphere and extended across the corpus callosum into the right hemisphere. The mass obliterated the corpus callosum and frontal horns of the lateral ventricles. The lateral ventricles were slightly dilated, but there was no dilation or elongation of the third ventricle or displacement of adjacent hypothalamic structures. Microscopic examination revealed a glioblastoma multiforme (Figure, C). In this case, the best explanation for sudden death is the mass effect of the tumor. However, the possibility of a seizure cannot be completely ruled out.

Case 9

A 39-year-old man was found unresponsive in bed. He had a history of seizure disorder and behavioral changes, which were attributed to severe head injuries sustained 10 years prior to death. He was being treated with antiepileptic medication.

General autopsy was unremarkable. The brain weighed 1620 g, and gross examination revealed extensive softening of the left superior and middle frontal gyri. There was no herniation of the temporal lobe unci or cerebellar tonsils. On coronal sections, the left frontal lobe exhibited a 3-cm cavitary lesion filled with necrotic and gelatinous material. In addition, softening and hemorrhagic discoloration of gray and white matter surrounded the lesion. Slight deviation of the midline from left to right was observed in the frontal lobes. The ventricular system was partially collapsed, but there was no deviation of the septum pellucidum or third ventricle. Microscopic sections revealed a malignant glioma. Although the brain of this individual had evidence of mass effect, that is, left to right shift and collapse of the ventricular system, the most likely explanation for his death is seizure.

Case 10

A 78-year-old man was the unrestrained driver and sole occupant of an automobile that crossed the center line and hit another vehicle head on.

At autopsy, general examination was remarkable for lacerations of the aorta and pulmonary artery, a fracture of the sixth cervical vertebra, and multiple rib fractures. The brain weighed 1360 g, and macroscopic examination revealed mild cortical atrophy in the frontoparietal lobes. At the base, a lesion measuring 5.5 x 4.0 cm was noted in the region of the pituitary gland and inferior surface of the frontal lobes. This lesion was brown, irregular in shape, and had a consistency that varied from gelatinous to firm. On coronal sections, the lesion projected into and separated the anterior portion of the frontal lobes, wrapped around the optic nerves and chiasm, but did not infiltrate brain structures. Microscopic examination revealed a pituitary adenoma. It seems likely that the tumor played a direct role in this individual's death, either causing a seizure or compromising his vision. It is possible, however, that the accident and subsequent death were unrelated to the pituitary adenoma.

Case 11

A 45-year-old man died after his automobile left the road at a high rate of speed and impacted a tree. His past medical history was unremarkable.

General autopsy revealed multiple facial injuries. The brain weighed 1690 g and the cerebral hemispheres were diffusely swollen. There was no herniation of the temporal lobe unci or cerebellar tonsils. On coronal sections, a mass measuring 4 cm in diameter was observed in the right frontal lobe white matter. This mass had a variegated appearance and contained regions of necrosis and hemorrhage. The mass extended into the left hemisphere through the anterior corpus callosum and obliterated the frontal horn of the right lateral ventricle. The right cingulate gyrus demonstrated minimal herniation. Microscopic examination revealed a glioblastoma multiforme. While .seizure is the most likely explanation for this accident, the possibility of an accident unrelated to the tumor cannot be excluded.

COMMENT

We present 11 cases of sudden deaths due to undiagnosed primary CNS tumors discovered at autopsy during a period of 20 years (1980-1999). These 11 cases represent 0.02% of the 54 873 autopsies performed at the Office of the Chief Medical Examiner of the State of Maryland during this time period. In an additional 16 cases out of the 76 listed in Table 1, deaths may have been caused by undiagnosed primary CNS tumors, but the medical information available was insufficient to determine if the tumors were the cause of death or if an antemortem diagnosis had been made. Thus, the incidence of undiagnosed brain tumors causing death in our study could potentially be as high as 0.05% if all 16 of these additional "undetermined" cases were included.

The last review of this subject, published 20 years ago by DiMaio and colleagues? involved 10995 consecutive autopsies performed by the Dallas County Medical Examiner's Office in Texas from January 1970 through December 1977. The authors found unsuspected primary intracranial neoplasms caused death in 0.17% of their cases.[2] Yet earlier studies of 17 404 autopsies at the Brooklyn Office of the Medical Examiner in New York and 3543 autopsies at the Kern County Coroner's Office in Bakersfield, Calif, identified undiagnosed CNS neoplasms resulting in death in 0.16% and 0.4% of cases, respectively.[3,4]

We observed a significantly lower incidence of deaths due to undiagnosed CNS tumors compared to earlier studies (Table 2). Although the series were collected from different locations, the autopsies in all 4 studies were performed at medical examiners' offices, and the methodologies used were similar; that is, deaths due to previously undiagnosed primary CNS neoplasms were identified on retrospective review. Earlier studies included cases in which the tumor was thought to cause death by precipitating a motor vehicle accident or drowning. We therefore also included all such cases in our review to maintain a homogeneous methodology. The populations involved in the 3 most recent studies are all large and predominantly urban, and variations in demographics are unlikely to account for the observed differences. Rather, we believe that the advent of advanced imaging techniques, such as magnetic resonance imaging and computed tomographic scanning, has resulted in fewer cases of CNS neoplasia escaping medical attention. In keeping with this hypothesis, the apparent increase in CNS cancer rates during the last 15 years is now thought to reflect a temporary phenomenon due to improved technology and earlier detection.[5,6]
Table 2. Undiagnosed Central Nervous System (CNS) Tumor Studies

 Study Location Years

Huntington et al,(4) Kern County, California 1950-1955
DiMaio and DiMaio,(3) Brooklyn, New York 1960-1970
DiMaio et al,(2) Dallas County, Texas 1970-1977
This study Maryland 1980-1999

 Undiagnosed
 CNS Tumor
 Study Autopsies Deaths, %

Huntington et al,(4) 3543 0.42
DiMaio and DiMaio,(3) 17 404 0.16
DiMaio et al,(2) 10 995 0.17
This study 54 873 0.02-0.05


As advanced imaging techniques were less commonly available in the 1980s than in the 1990s, we thought a significant decrease in undetected tumors in the second decade of our study would support a role for imaging in improved detection. In fact, the number of undiagnosed CNS tumors decreased slightly over the course of our study, with 6 of the 11 cases we present occurring in the 1980s and 5 occurring in the 1990s. However, this change is too small to support or refute our hypothesis that improved imaging has played a role in the decreased incidence.

The largest group of neoplasms in our series consisted of 7 glial lesions of varying grade: 1 grade II diffuse astrocytoma, 1 grade III anaplastic astrocytoma, 1 malignant glioma not otherwise specified, and 4 grade IV glioblastoma multiforme. The preponderance of this group is not surprising; astrocytic lesions are the most common type of brain tumor, accounting for more than 38% of all primary CNS lesions, and they are generally fatal.[1] Two colloid cysts, 1 schwannoma, and 1 pituitary adenoma made up the remaining 4 cases. The mechanisms of death included seizures, acute hemorrhage, and herniation due to mass effect. Recent case reports and reviews of the literature have highlighted similar scenarios.[7-10]

Seven of the patients did not seek medical attention prior to their deaths. Four of these 7 patients were symptomatic, but the short duration of symptoms, poor access to health care, or other factors may have prevented them from seeing a doctor. The remaining 4 patients were under the care of a physician. In these cases, vague or misleading symptoms and the presence of concurrent medical conditions likely obscured the correct diagnosis. One patient (case 2) died prior to having his scheduled diagnostic procedure (spinal magnetic resonance imaging). Three other patients were treated initially for neck strain (case 4), migraine headache (case 6), and seizures presumed to be secondary to past trauma (case 9). Similar scenarios have been reported previously. For example, Aronica and colleagues recently described the case of an adolescent boy being treated with sumatriptan succinate for migraines, who died suddenly due to a colloid cyst of the third ventricle.[11] Indeed, sudden death due to colloid cysts is a well-described phenomenon; more than 40 cases have been reported in the literature to date.[11-18]

The case involving the pregnant woman (case 4) raises the issue of hormone-driven tumor growth causing acute medical complications. A pregnant woman presenting with vomiting and headache usually creates suspicion for eclampsia, but it is also important to consider the possibility of a hormone-responsive tumor in these cases. Dramatic increase in the size of meningiomas expressing receptors for progesterone and other hormones in pregnant women is a well-documented phenomenon.[19,20] The data concerning hormone responsiveness in schwannomas is less clear-cut. However, a subset of these tumors were found to express hormone receptors in several studies,[21,22] and preliminary experiments using tumors implanted in nude mice support the concept that hormones can modulate schwannoma growth.[23]

In summary, our data support a decline in the percentage of sudden deaths due to undiagnosed brain tumors. This decrease is most likely due to improved detection methods, such as computed tomography and magnetic resonance imaging, and may reflect improved access to health care. However, even with these improvements, a baseline number of patients still die due to unsuspected or undiagnosed brain tumors. These cases highlight the importance of considering a primary CNS neoplasm in patients with vague symptoms or in patients not responding to therapy.

References

[1.] Year 2000 Standard Statistical Report. Chicago, Ill: Central Brain Tumor Registry of the United States; 1999.

[2.] DiMaio SM, DiMaio VJM, Kirkpatrick JB. Sudden, unexpected deaths due to primary intracranial neoplasms. Am J Forensic Med Pathol. 1980;1:29-45.

[3.] DiMaio TM, DiMaio DJ. Sudden death due to colloid cysts of the third cerebral ventricle. N Y State Med J. 1974;74:1832-1834.

[4.] Huntington RW, Cummings KL, Moe TI, O'Connell HV, Wybel R. Discovery of fatal primary intracranial neoplasms at medicolegal autopsies. Cancer. 1965; 18:117-127.

[5.] Reis LAG, Smith MA, Gurney JG, eds. Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program; 1999. National Institutes of Health publication 99-4649.

[6.] Legler JM, Reis LA, Smith MA, et al. Brain and other central nervous system cancers: recent trends in incidence and mortality. J Natl Cancer Inst. 1999;91: 1382-1390.

[7.] Prahlow JA, Teot LA, Lantz PE, Stanton CA. Sudden death in epilepsy due to an isolated subependymal giant cell astrocytoma of the septum pellucidum. Am J Forensic Mod Pathol. 1995;16:30-37.

[8.] Buttner A, Gall C, Mall G, Weis S. Unexpected death in persons with symptomatic epilepsy due to glial brain tumors: a report of two cases and review of the literature. Forensic Sci Int. 1999;100:127-136.

[9.] Gleckman AM, Smith TW. Sudden unexpected death from primary posterior fossa tumors. Am J Forensic Med Pathol. 1998;19:303-308.

[10.] Byard RW, Bourne AJ, Hanieh A. Sudden and unexpected death due to hemorrhage from occult central nervous system lesions: a pediatric autopsy study. Pediatr Neurosurg. 1991-92;17:88-94.

[11.] Aronica PA, Ahdab-Barmada M, Rozin L, Wecht CH. Sudden death in an adolescent boy due to a colloid cyst of the third ventricle. Am J Forensic Med Pathol. 1998;19:119-122.

[12.] MacDonald RL, Humphreys RP, Rutka JT, Kestle JR. Colloid cysts in children. Pediatr Neurosurg. 1994;20:169-177.

[13.] Leestma JE, Konakci Y. Sudden unexpected death caused by neuroepithelial (colloid) cyst of the third ventricle. J Forensic Sci. 1981;26:486-491.

[14.] Opeskin K, Anderson RM, Lee KA. Colloid cyst of the 3rd ventricle as a cause of acute neurological deterioration and sudden death. J Paediatr Child Health. 1993;29:476-477.

[15.] Torrey J. Sudden death in an 11-year-old boy due to rupture of a colloid cyst of the third ventricle following `disco-dancing.' Med Sci Law. 1983;23:114-116.

[16.] Kuchelmeister K. Colloid cysts of the 3rd ventricle: an underestimated danger? Neurochirurgia. 1992;35:5-8.

[17.] Byard RW, Moore L. Sudden and unexpected death in childhood due to a colloid cyst of the third ventricle. J Forensic Sci. 1993;38:210-213.

[18.] Buttner A, Winkler PA, Eisenmenger W, Weis S. Colloid cysts of the third ventricle with fatal outcome: a report of two cases and review of the literature. Int J Legal Med. 1997; 110:260-266.

[19.] Wan WL, Geller JL, Feldon SE, Sadun AA. Visual loss caused by rapidly progressive intracranial meningiomas during pregnancy. Ophthalmology. 1990; 97:18-21.

[20.] Saitoh Y, Oku Y, Izumoto S, Go J. Rapid growth of a meningioma during pregnancy: relationship with estrogen and progesterone receptors. Neurol Med Chir. 1989;29:440-443.

[21.] Carrol RS, Zhang JP, Black PM. Hormone receptors in vestibular schwannomas. Acta Neurochir. 1997;139:188-192.

[22.] Monsell EM, Wiet RJ. Estrogen and progesterone binding by acoustic neuroma tissue. Otolaryngol Head Neck 5urg. 1990;103:377-379.

[23.] Stidham KR, Robertson JB Jr. Effects of estrogen and tamoxifen on growth of human vestibular schwannomas in the nude mouse. Otolaryngol Head Neck Surg. 1999;120:262-264.

Accepted for publication March 22, 2001.

From the Departments of Pathology (Drs Eberhart and Troncoso, and Mr Frazier) and Neurology (Dr Troncoso), Johns Hopkins University School of Medicine, Baltimore, Md; the Department of Neuropathology, Armed Forces Institute of Pathology, Bethesda, Md (Dr Morrison); the Department of Pathology, University of Maryland, School of Medicine, Baltimore (Drs Gyure and Smialek); and the Office of the Chief Medical Examiner of the State of Maryland, Baltimore (Dr Smialek).

Reprints: Juan Troncoso, MD, Johns Hopkins School of Medicine, Department of Pathology, 558 Ross Research Bldg, 720 Rutland Ave, Baltimore, MD 21205-2196 (e-mail: troncoso@jhmi.edu).
COPYRIGHT 2001 College of American Pathologists
No portion of this article can be reproduced without the express written permission from the copyright holder.
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Author:Eberhart, Charles G.; Morrison, Alan; Gyure, Kymberly A.; Frazier, James; Smialek, John E.; Troncoso
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Statistical Data Included
Geographic Code:1USA
Date:Aug 1, 2001
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