Immunohistochemical expression of receptor tyrosine kinase PDGFR-α, c-Met, and EGFR in skull base chordoma.

Chordomas are rare, locally aggressive malignancies that often exhibit an insidious natural history and are difficult to eradicate. Surgery and radiotherapy are the treatment mainstays of chordoma, but the chance of local recurrence remains high. Reports of receptor tyrosine kinase (RTK) expression in chordoma suggest that these tumors may respond to kinase inhibitor therapy. Currently, there are no effective chemotherapeutic protocols for chordoma. A tissue microarray containing 74 tumor specimens from primary chordoma patients and 71 from their recurrent tumors for a total of 145 tumor specimens was immunohistochemically analyzed for expression of a number of proteins involved in signal transduction from RTKs. Platelet-derived growth factor receptor-α (PDGFR-α), epidermal growth factor receptor (EGFR), c-Met, and CD-34 were detected in 100, 92, 100, and 59% of cases, respectively. PDGFR-α and c-Met staining was of moderate to strong intensity in all cases. In contrast, total EGFR staining was variable; weak staining was detected in 10 cases. Our results contribute to the understanding of the expression of RTKs in skull base chordomas and support the development of targeted therapies that inhibit RTKs, which may have a synergistic effect for chemotherapy in patients. There were statistically significant correlations between the expression of PDGFR-α, c-Met, and EGFR and disease-free survival. The results nonetheless suggest that chordomas may respond to RTK inhibitors or modulators of other downstream signaling.

Dementia and leukoencephalopathy due to lymphomatosis cerebri.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). Clinically, the disease typically presents with a rapidly progressive dementia and unsteadiness of gait. Its presentation on cerebral MRI, which is characterised by diffuse leukoencephalopathy without contrast enhancement, often causes diagnostic confusion1 with suspected diagnoses ranging from Binswanger's disease to leukoencephalopathy or encephalomyelitis. Here we report a patient with subacute dementia and diffuse bilateral white matter changes in the cerebral hemispheres and additional involvement of the brainstem, basal ganglia and thalamus on MRI. Initially, she was considered to suffer from an autoimmune encephalitis, transiently responded to immunosuppression but then developed multiple solid appearing cerebral lymphomas.