Contributed by Hans Brunnström1, Michael Dictor1, Christer Nilsson2, Dag Gülich2, Elisabet Englund1
1Department of Pathology; 2Department of Geriatric Psychiatry; Lund University, Lund S-22185, Sweden
A 76-year-old man presented with progressively worsening vertigo, memory and concentration impairment, spatial disorientation and mild expressive dysphasia for 6 months. His medical history included hypertension and a surgically treated abdominal aortic aneurysm. A few weeks before admission, headache, fatigue, weakness of the lower limbs and left arm, a tendency to fall to the left, incontinence, and episodes of confusion occurred. Upon admission the patient showed marked fatigue, confusion and apathy, and a contrast-enhancing round lesion, 1 cm in diameter, was seen in the left temporal lobe on magnetic resonance imaging (MRI). Repeated cognitive testing demonstrated fluctuating deficits in language, working and episodic memory, visuospatial ability, attention and psychomotor speed. A second MRI, performed one month after the first, showed attenuation of the previous lesion, with general signal enhancement in the leptomeninges, a heterogeneous contrast-enhancing lesion measuring 1x2 cm in the left frontal lobe, and a smaller lesion near the left sylvian fissure (Figure 1).
There was no sign of infection, and blood tests were normal. Repeated lumbar punctures were performed; cerebrospinal fluid (CSF) analyses showed slightly elevated counts of mononuclear cells (7-10 x 106 cells/L) that were cytologically normal. There was evidence of severe blood brain barrier disruption with elevated albumin levels and oligoclonal IgG bands on electrophoresis. The levels of neurodegenerative markers were increased with a total tau of 910 ng/L (ref <400) and neurofilament protein of 2540 ng/L (ref <750). Extensive screening for infectious agents was negative. Octreotide scintigraphy (octreotide used as a radiolabelled somatostatin analogue for detection of neuroendocrine tumours, granulomatous disease, et cetera) showed uptake in the frontal and temporal lobe lesions (Figure 2), a finding which led to the diagnostic suggestion of neurosarcoidosis and to subsequent medication with high dose corticosteroids. Initially, the treatment appeared to have a beneficial effect, but the condition soon deteriorated clinically and radiologically. Four months after the start of treatment the patient died from aspiration pneumonia following a seizure episode.
Macroscopically, a tumour-like mass, 5x4x3 cm in size with poorly defined margins, was found in the centre of the left frontal lobe within the white matter (Figure 3; Luxol fast blue stain). No other lesions were seen in the brain or the meninges.
Microscopic examination revealed a diffuse mononuclear cell infiltrate with variable cell density infiltrating the neuropil rather than growing in sheets. The cells were small with a lymphoid appearance and round, oval or irregular nuclei, inconspicuous nucleoli, and scant cytoplasm (Figure 4 and 5; haematoxylin-eosin stain). Scattered mitoses, as well as necrotic areas and oedema, were present, and cells infiltrated the meninges, perivascular spaces and vessel walls. The infiltrates extended from the left into the right frontal lobe, but were absent in the temporal and parietal lobes. The affected brain tissue exhibited some reactive gliosis, mainly in the white matter, but no granulomas or plasmacytoid cells were detected. The histology was neither typical of a central nervous system (CNS) lymphoma nor of an inflammatory disease.
Immunohistochemically, the vast majority of the infiltrating cells stained positive for CD3 (Figure 6) and over half of them were positive for CD2 and T-cell intracellular antigen 1 (TIA1). Almost half of the cells were positive for the activated T-cell marker granzyme B, and some for CD7. Occasional lymphocytes expressed CD4, CD5, CD8 and CD30, while staining for the B-cell marker CD20 and for CD56, activin receptor-like kinase 1 (Alk1) and T-cell receptor alpha/beta (TCR alpha/beta) was consistently negative.