Contributed by Henda Foreid1, Cândida Barroso1, Herculano Carvalho2, Carlos Morgado3, Lúcia Roque4, José Pimentel1
1 Laboratory of Neuropathology, Hospital de Santa Maria; Institute of Molecular Medicine, Lisbon Faculty of Medicine, Lisbon
2 Department of Neurosurgery, Hospital de Santa Maria, Lisbon
3 Department of Neurological Imagiology, Hospital de Santa Maria, Lisbon
4 Laboratory of Cytogenetics, Instituto Português de Oncologia de Francisco Gentil, Lisbon
A 22-year-old man presented with short-term complaints of headache, vomiting and diplopia. On neurological examination, bilateral papilledema and left abducent nerve palsy were seen. Brain Magnetic Resonance Imaging (MRI) disclosed, both in FLAIR and enhanced T1-weighted sequences, a diffuse leptomeningeal enhancement over cerebral and cerebellar hemispheres (Fig. 1), which assumed a nodular-like appearance over the vermis (Fig. 2). No intraparenchymal mass was elicited. A lumbar puncture of cerebrospinal fluid (CSF) showed an opening pressure of 360 cm H2O, and the CSF chemistry, low glucose level (1.1 mg/dl) and normal protein and cell count. CSF cytological analysis, viral serology and cultures were negative. No abnormalities were found in Angiotensin-Converting Enzyme (ACE), beta-2 microglobulin, alpha-fetoprotein (AFP) and PCR levels. The patient was started on corticotherapy with significant neurological improvement, but after discontinuing steroids, headache and visual complaints renewed, and new-onset gait disturbance and impaired sensibility over the perineum and left foot were noticed. Fifth, sixth and seventh cranial nerve palsies, gait ataxia, and perineal pinprick hypoesthesia with a saddle distribution were then elicited. An enhanced MR imaging of the spine revealed a leptomeningeal enhancement of cervical and lower dorsal segments, down to the conus medullaris and cauda equine. Again, CSF cytology was unremarkable. Also, the neuropathological examination of a small fragment of the left cerebellar hemisphere, obtained by stereotactic biopsy, was considered normal. Extensive imaging studies failed to identify a systemic neoplasm. Shortly after discharge, the patient came back with bilateral amaurosis. A brain computer tomography (CT) disclosed a marked hydrocephalus and a ventriculoperitoneal shunt was then performed. This time, CSF cytology was abnormal, and a second cerebellar stereotactic biopsy, this time of the vermis, was undertaken.
CSF cytology - clusters of small round neoplastic cells with high nuclear/cytoplasmic ratios, showing nuclear moulding and the presence of abundant apoptotic bodies. Diffuse synaptophysin (Fig. 3) and focal GFAP immunoreactivity.
Neuropathological examination of the vermis specimen- seen at an extra- axial, apparently leptomeningeal location, but in continuity with the cerebellar parenchyma, there were poorly differentiated, sheet-like arranged aggregates of neoplastic elements with scanty cytoplasm and closely packed, round, small, hyperchromatic nuclei, on a moderate, fibrillary background stroma (Fig. 4). No mitosis could be seen but apoptotic bodies were a prominent feature. Immunohistochemical study disclosed extensive reactivity for vimentin and neurofilaments (Fig. 5), focal reactivity for synaptophysin (Fig 6) and GFAP (Fig. 7), and absent reactivity for CD99, AE1+AE3, CD3 and CD20.
Cytogenetical analysis by FISH assay, looking for the presence of imbalance on MYCC gene and EWS rearrangement was negative.