Contributed by Fernandez-Vega I1, Saiz A2, Santos-Juanes J1, Piņa-Batista K3, Corte-Torres MD4, Astudillo A1
Departments of 1Pathology (Neuropathology Division), 2Neuroradiology, 3Neurosurgery and 4IUOPA Biobank, Hospital Universitario Central de Asturias, Oviedo, Spain
A previously healthy 64 years old woman was admitted to our hospital arguing generalized fatigue, sleep impairment, mild weight loss and chronic progressive headache, becoming holocranial and resistant to many drugs during last few months. The patient was alert and orientated. No papilledema but slightly neck stiffness was noted. Cranial nerve functions were intact.
Initial computed tomography (CT) of the brain and spine did not show any remarkable alteration. In a posterior magnetic resonance imaging (MRI), after gadolinium administration, a leptomeningeal enhancement was identified. Biochemical and cytological Light Chain Ratio (LCR) study was unremarkable. Because of the possibility of chronic tuberculous meningitis and while waiting for LCR culture, she underwent antituberculostatic treatment. However, no growth was detected in any of the bacterial cultures of the LCR. A month later she was readmitted to the hospital because of the progressive symptoms. A second MRI was performed without any further information. Surgical biopsy of arachnoid and frontal cortex was made showing idiopathic hypertrophic pachymeningitis. After four months of the last craniotomy and because of the patient's symptomatic progression, a second surgical biopsy was carried out. A new MRI was also done. A huge increase of leptomeningeal enhancement involving the whole brain and also in the M1 segment of the right middle cerebral artery was noted (Figure 1), comparing to the previous MRIs. Beside, mainly the upper part of the spinal cord also showed an increase of leptomeningeal enhancement (Figure 2). Despite high doses of corticosteroid therapy, she developed upper extremity paresis, became increasingly cachectic and confused, developed tetraventricular hydrocephalus, got into coma and finally died 6 months later of first admission.
The postmortem (PM) demonstrated leptomeningeal opacification with areas of whitish thickening, affecting mainly base of the brain and the upper part of the spinal cord (Figure 3). Coronal sections did not find any tumoral mass neither in the parenchyma nor in the ventricles. There was a softening of parenchyma concerning the right cerebral media vascular territory and also well delineated small cortical infarctions involving both gyrus cinguli (Figure 4). A remarkable finding was the wall thickening of the major cerebral arteries (Figures 5 and 6).
Microscopic examination showed a malignant diffuse leptomeningeal proliferation composed of an admixture of ovoid and spindle-shaped cells, showing irregular and vesicular or multilobulated nuclei, with eosinophilic cytoplasm. The malignant cells were infiltrating leptomeninges and also going through the Virchow-Robbins spaces, but not evidence of parenchymal invasion was noted, in spite of multiple serial sections (Figure 7). Some abnormal mitoses were observed, but endothelial proliferations and necrosis were absent. Moreover, some images of infarction and vascular recanalization were noted (Figures 8 and 9). On immunohistochemistry, tumor cells were strongly positive for GFAP (Figures 10 and 11). The tumor cells were considered negative for p53 (Figure 12). Ki-67 proliferation was up to 5% in different tumoral zones (Figure 13). IDH 1 immunohistochemistry was negative. What is your diagnosis?