Contributed by Tim Williams, MD, John Taylor, DO, and William Hickey, MD
Department of Pathology (TW,WH) and Neurology (JT) Dartmouth Medical School
DIAGNOSIS AND DISCUSSION:
Dx: Gliomatosis Cerebri
Gliomatosis cerebri (GC, or diffuse infiltrating astrocytoma) is a rare brain neoplasm characterized grossly by enlargement, often subtle, of affected brain regions with preservation of native CNS architecture and absence of a discrete tumor mass. Microscopically, the tumor consists of proliferating malignant glial cells which diffusely infiltrate large areas of the CNS, involving more than two lobes, and often involving both supratentorial and infratentorial brain regions .
The majority of patients diagnosed with GC are relatively young (median age 44 ), and experience insidiously progressive symptoms which can include headaches, alteration of mental status and cognition, dysphasia, visual deficits, hemiparesis, and seizures. Often these cases present significant diagnostic challenges to clinicians, and final diagnoses are not made until postmortem examination. Even when diagnosed antemortem, therapeutic options are minimal and prognoses grim.
Invariably the mechanism of death in cases of GC is compressive sequelae from expanding intracranial mass. In glial tumors generally, such expansion is thought to occur secondary to cerebral edema due to disruption of the blood-brain barrier (BBB) in tumor microvasculature and, possibly, altered tumor cell expression of transmembrane proteins normally operative in fluid homeostasis . In GC, direct cerebral expansion from increased cellular mass may also play a role.
The sudden death of this patient suggests catastrophic failure of intracerebral fluid homeostasis. Premortem episodes of severe headache may have been due to intermittent, less complete instances of BBB breakdown.
1. Eberhart CG, et al. Decreasing incidence of sudden death due to undiagnosed
primary central nervous system tumors. Arch Pathol Lab Med. 2001; 125: 1024-30.
2. Lantos PL, et al. Gliomatosis cerebri. In: Kleihues P, et al, editors. WHO Classification of Tumours: Tumours of the Central Nervous System. Pathology and Genetics. IRAC Press, Lyon, 2000.
3. Chamberlin MC. Gliomatosis cerebri: Better definition, better treatment. Neurology. 2004; 63: 204-5.
4. Papadopoulos MC, et al. Molecular mechanisms of brain tumor edema. Neuroscience. 2004; 129: 1011-20.