|Contributed by Stefan Isenmann, MD1, Christian Aepinus, MD2, Martin Skalej, MD3, Antje Bornemann, MD4, Ernst H. Grote, MD5
University of Tübingen Medical School, D-72076 Tübingen, Germany; Departments of 1Neurology, 2Molecular Pathology, 3Neuroradiology, 4Neuropathology, 5Neurosurgery
A 35-year-old male presented after he had experienced two episodes of difficulties in word finding lasting less than 20 minutes each earlier in the day. Physical and neurological examination were completely normal except for litteral paraphasias in two instances within one hour of history taking. Extensive routine laboratory examination was completely normal; there were no hints of immunodeficiency. Serologic tests for neurotropic viruses were inconspicuous. Bacterial and parasite serology was negative except IgG titers against toxoplasmosis, while IgA and IgM both were negative, indicating latent infection. EEG showed a left fronto-temporal theta/delta focus.
A CT scan showed a 15 x 15 mm ring enhancing left temporal mass surrounded by marked perifocal edema (Fig. 1a). A MRI scan showed no further lesions; cerebral angiography revealed arterial displacement, but no tumor blush (not shown). Under the assumption of malignant glioma, the patient was immediately treated with dexamethasone, and the lesion was biopsied. In order to avoid operation-induced neurological deterioration (severe aphasia), only a small part of the lesion was biopsied, and the major part left untouched (Fig. 1b).
Histological examination of the biopsy revealed a non-specific inflammatory infiltrate consisting mainly of macrophages and lymphocytes (Fig. 2a), and containing necrotic areas (Fig. 2b). There was some astrogliosis present, but no glial tumor cells. Immunocytochemical stainings failed to show predominance of either B- or T-cell populations. Additional stainings for bacteria and fungi (PAS, Giemsa, Ziehl-Neelsen, Auramin, Grocott, Gram) all did not show any specific pathogens. Immunocytochemistry for toxoplasma antigen was also negative (not shown). Taken together, ample histological examinations failed to yield a precise diagnosis.
MOLECULAR BIOLOGIC ANALYSIS:
DNA was isolated from the tissue specimen. PCR analysis for immunoglobulin chains, and T cell receptors failed to reveal clonal arrangements indicative of either B- or T-cell lymphoma. However, PCR analysis with two independent primer pairs demonstrated the presence of Toxoplasma gondii DNA (Fig. 3). Lanes 1 - 3 represent a PCR for Toxoplasma gondii 18s rRNA (product: 88 bp; Ref. 4); lanes 5 - 7 represent a PCR for the Toxoplasma gondii B1 gene (product: 190 bp; Ref. 6). Lanes 1 and 5 are derived from the patient's biopsy specimen (P), and show specific bands; 2 and 6, negative control (-); 3 and 7, positive control (+); 4, marker (M).