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BMJ Case Rep. 2010; 2010: bcr10.2009.2378.
Published online Mar 30, 2010. doi:  10.1136/bcr.10.2009.2378
PMCID: PMC3029984
Unexpected outcome (positive or negative) including adverse drug reactions
Sudden death due to medulloblastoma
Gentian Vyshka,1 Elmaz Shaqiri,2 and Besim Ymaj2
1Faculty of Medicine, Rr Dibres, Tirana, 371, Albania
2Institute of Legal Medicine, Rr Dibres, Tirana, 371, Albania
Correspondence to Gentian Vyshka, gvyshka/at/yahoo.com
Abstract
Intracranial tumours can be accompanied with intracerebral and intracerebellar non-traumatic haemorrhage; in some cases, this might be their first clinical sign. We report a case of a man who suffered sudden death due to medulloblastoma, with intratumoral haemorrhage; his tumour had a hemispheric cerebellar positioning. The cerebral oedema seen at autopsy reflected the immediate cessation of cerebral vascular circulation, leading to sudden death. Acute obstructive hydrocephaly is a mechanism widely known in the literature for causing sudden death.
Primitive neuroectodermal tumours are a group neoplasms whose prototype is represented by medulloblastoma. The latter is part of a group of embryonal malignancies, with small cells, showing different stages of differentiation toward specific neuronal cellular lines, sometimes glial lines, and rarely mesenchymal ones. In rare cases the literature describes a sudden deterioration of neurological status, and eventually sudden death; both situations are related to an acute intratumoral haemorrhage, combined with medullar/truncal compression due to mass effect. The diffusion of tumoral cells via the cerebrospinal fluid route and hydrocephaly related to the acute mass effect are some other pathogenetic mechanisms.
An autopsy was performed on the body of a 21-year-old man who, the day before his sudden death, was urgently admitted to a regional hospital in southern Albania. The person died immediately upon arrival at the emergency department, and forensic experts examined the external view of the body and performed the autopsy.
The external view suggested some abrasions to the face and hands, but no damage could be related to any violent causal factor. Toxicological data ruled out the probability of intoxication.
The autopsy showed intracranially on the left cerebellar hemisphere, upper side, a homogenous softening of the cerebellar structure, with loss of normal structures of the lobule, pointing to destruction of the cerebellar mass. The macroscopic view of the right cerebellar hemisphere was normal.
Histology (figs 1 and and2)2) of the cerebellum showed an impressive cellularisation formed from round shaped cells, creating a lining fascet and sometimes a rosette-like aspect. The cells were similar to small lymphocytes, and their cellular and nuclear atypical aspect was discrete. Isolated regions of the tumoral mass were necrotic and coagulated blood, partially thrombotic, was detected.
Figure 1
Figure 1
Histological preparation from the medulloblastoma, showing haemorrhage and intratumoral coagulation. Haematoxylin and eosin (H&E).
Figure 2
Figure 2
Histological preparation from the medulloblastoma, similar to that shown in fig 1.
The anatomical/pathological diagnosis was that of a cerebellar tumour (medulloblastoma) with secondary acute changes (focal necrosis, haemorrhage and partial thrombosis, with oedema of the tumoral mass and of the entire brain structure generally). The peritumoral area showed pronouned oedema (fig 3), and the cellularity was impressive (fig 4). The cerebellar tissue was dissected, fixed in blocs of paraffin, and sections were then cut and examined (fig 5).
Figure 3
Figure 3
Intracellular oedema in the peritumoral zone (H&E).
Figure 4
Figure 4
Medulloblasts inside the tumoral area (H&E).
Figure 5
Figure 5
Macroscopic view of the cerebellar hemisphere, with marginal haemorrhage.
The forensic experts concluded that the cerebellar tumour (medulloblastoma) was the causal factor in the subject’s sudden (immediate) death, the tumour having a mass effect upon the medullar structures, resulting in abrupt central cardiovascular failure from which the subject had no chance of survival.
Medulloblastoma is a malignant tumour of the posterior fossa, occurring mainly during childhood although adult cases have been increasingly reported.1,2 The cerebellum is the usual region of localisation of medulloblastoma; when other foci are found, they are generally considered as multifocal and/or metastatic cerebellar medulloblastoma. There have been historically a few rare cases reporting cerebral medulloblastoma, although authors have questioned the existence of this form of tumour.3
More than 75% of cerebellar cases are vermian. More lateral localisations, eventually hemispheric ones, are more usual when the tumour is found during adolescence or adulthood. Our subject was 21 years old, and the localisation was hemispheric.
The change in localisation (vermian in childhood; lateral or hemispheric in adulthood) is hypothetically related to the migration of non-differentiated cells from the posterior medullar velum toward lateral and posterior directions.4 During the first years of life, these cells are localised next to the median line, and theoretically may cause a tumoral growth following this line—that is, in the cerebellar vermis. Later, these cells migrate laterally and the tumour growth will preferably tend toward a hemispheric localisation.5 The infiltration of the brain stem (truncal structures) is usual; other referred localisations are those of the fourth ventricle, other cerebellar regions, or even the spinal cord.1,6
The clinical history of medulloblastoma as a rule is very short, and reflects the aggressive biological behaviour of the tumour. The majority of these patients have a symptomatology of less then 3 months.7 Headache and vomiting are the usual complaints. Truncal ataxia following the severe damage to the vermis is an objective common sign, and is frequently associated with spasticity. Papilloedema (related to hydrocephaly), nystagmus, and sixth cranial nerve palsy are also found in these patients quite often.
In rare cases the neurological status may aggravate very quickly, and death (even sudden) may follow acute intratumoral haemorrhage. The haemorrhage creates an immediate mass effect on the posterior fossa, with an acute hydrocephaly and cessation of the intracranial circulation. The spinal cord compression due to the diffusion of tumoral cells via cerebrospinal pathways is also a phenomenon described in the literature.8
Other authors have explained the risk of sudden death explicitly in relation to the obstructive hydrocephaly, although doubts on the veracity of the hypothesis are expressed.9 An acute hydrocephaly is mostly cited by authors as the probable death mechanism, in comparison with the probability of a direct compression on the vital brain stem structures.
The World Health Organization classifies medulloblastoma as a fourth grade lesion, distinguishing four subtypes of the tumour: classical, desmoplastic, mainly nodular and with advanced neuronal differentiation, and with large cells.2
In conclusion, intracranial tumours might be accompanied by non-traumatic intracerebral and intracerebellar haemorrhage; in some cases such a haemorrhage might be the first clinical sign. Intracranial tumours that can result in sudden death include multiform glioblastoma,10 oligodendroglioma, medulloblastoma, lymphoma, teratoma, etc.
We report the case of sudden death of a 21-year-old man, due to hemispheric cerebellar medulloblastoma with intratumoral haemorrhage. The cerebral oedema found at the autopsy reflected the immediate cessation of the cerebral circulation, obviously due to the acute obstructive hydrocephalus during the cascade of the pathological events at the peri-aqueductal region.
Learning points
  • Sudden death due to intracranial disorders in adulthood represents a major challenge to forensic experts. Among the causative mechanisms mentioned by authors11 are:
    • prompt increase of intracranial pressure, due to haemorrhage in different brain territories
    • acute obstructive hydrocephalus
    • autonomous and/or neurochemical dysfunction, in rare cases of immediate death; the autonomous hyperactivity is thought to be transmitted through lower cranial nerves, or is thought to be related to high concentrations of epinephrine or norepinephrine secreted in the systemic circulation, probably as a part of the ‘response toward stress’.12
  • The most quoted mechanism of death according to different authors is the prompt increase in intracranial pressure, mainly in cases of massive haemorrhage, with the possibility of a total cessation of cerebral circulation. On the other hand, patients suffering a haemorrhage in the vicinity of the ventricular system, and particularly in the posterior fossa, might show an acute obstructive hydrocephalus.
  • In our case the mechanism of the acute obstruction following the haemorrhage was plausible, because autopsy showed evidence of blood coagulum and intratumoral bleeding, with immediate blocking of the aqueduct at the level of the fourth ventricle.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
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8. Tomita T, McLone DG. Spontaneous seeding of medulloblastoma: results of cerebrospinal fluid cytology and arachnoid biopsy from the cisterna magna. Neurosurgery 1983; 12: 265–7. [PubMed]
9. Koeller KK, Rushing EJ.: Medulloblastoma: a comprehensive review with radiologic-pathologic correlation. Radiographics 2003; 23: 1613–37. [PubMed]
10. Di Maio SJ, Di Maio VJM, Kirkpatrick J. Sudden death due to primary intracranial neoplasm. Am J Forensic Med Pathol 1980; 1: 29–46. [PubMed]
11. Black M, Graham DI. Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol 2002; 55: 44–50. [PMC free article] [PubMed]
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