Case 810 -- A 58-year-old male with hallucinations and atasxia

Contributed by Yee Lin Tang, MBBS*, Wai Hoe Ng, MBBS, MD, FRACS^, Yih Yian Sitoh, MBBS, FRCR#, Hwei Yee Lee, MBBS, FRCPath*, Wai Ming Yap, MBBS, FRCPath*, Khoon Leong Chuah, MBBS, FRCPA*
* Department of Pathology, Tan Tock Seng Hospital, Singapore; ^ Department of Neurosurgery, National Neuroscience Institute (TTSH Campus) and Duke-NUS Graduate Medical School, Singapore; # Department of Neuroradiology, National Neuroscience Institute (TTSH Campus), Singapore


A 58 year old Caucasian male presented with weight and appetite loss over 2 to 3 months. He was recently diagnosed with human immunodeficiency virus (HIV) infection. His initial CD4 count was < 20cells/mm3 (7%) with a viral load of 352000 copies/ml. He was commenced on highly active antiretroviral therapy (HAART) and in the third month of therapy, he presented with increasing hallucinations and ataxia. Serologies for hepatitis A, hepatitis B, cytomegalovirus (CMV), toxoplasma, syphilis, tuberculosis (TB) and Cryptococcus neoformans were negative. His cerebrospinal fluid (CSF) profile was negative for Cryptococcus neoformans, TB, herpes simplex virus (HSV), CMV, toxoplasma, varicella zoster virus (VZV) and Epstein Barr virus (EBV) were negative. In addition, his CD4 count rose to 202 cells/mm3 with a viral load of 425 copies/ml.

Magnetic resonance imaging (MRI) showed an area of heterogeneous contrast enhancement affecting the deep nuclei as well as white and grey matter tracts with extension into the deep white matter of the right frontal, temporal and parietal lobes. This area exhibited mild mass effect compressing on the left lateral and third ventricles with early midline shift to the left (Fig. 1). JC virus was detected in his CSF by PCR, but in view of the radiological findings, a clinical diagnosis of lymphoma was considered and the patient underwent a brain biopsy to ascertain the nature of the brain lesion.


Grossly, multiple fragments of brain tissue measuring 2x1x1cm were received. On light microscopy, there was a prominent and dense perivascular infiltrate of lymphoid cells distending the walls of the blood vessels (Fig. 2), raising the suspicion for a neoplastic lymphoid proliferation. On closer scrutiny, the inflammatory cells comprised atypical medium to large lymphoid cells with some degree of irregular nuclear outlines (Fig. 3). Some smaller lymphoid cells accompanied the infiltrate. Significantly, the adjacent brain parenchyma showed a mixture of foam cells, similar lymphoid cells as those described above and plasma cells (Fig. 4). Interestingly, an occasional enlarged cell with bizarre and hyperchromatic nuclei was present within the inflammatory background (Fig. 5). Microglial nodules were also seen in some parts of the tissue. No acid fast bacilli and fungal organisms were noted on Ziehl Neelsen stain and Grocott methenamine silver stain respectively.

On immunohistochemistry, CD3 (Fig. 6) and CD20 (Fig. 7) stains highlighted the perivascular and brain parenchyma lymphoid cells with a predominance of CD 3+ T lymphocytes in the latter. CD163 confirmed the presence of histiocytes in the inflammatory lesion which assumed the appearance of foam cells in several places. Stains for toxoplasmosis and CMV were negative. Neurofilament stain confirmed the presence of the axonal processes in the areas with the histiocytes. A viral immunostain was diagnostic (Fig. 8). What is your diagnosis?


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