Malignant transformation of NF1-associated spinal astrocytoma with loss of ATRX expression during the course: A case report.

Few cases of malignant transformation of supposedly low-grade gliomas were described in patients with neurofibromatosis type 1 (NF1). A 27-year-old man with NF1 presented with weakness of his lower extremities and was radiologically found to have a spinal intramedullary tumor primarily involving the Th11 level. The tumor histologically demonstrated features diagnosed as a low-grade astrocytoma, subtype indeterminate (WHO grade II). Immunohistochemically, GFAP was positive, and IDH1 R132H and BRAF V600E were negative. ATRX immunoreactivity was retained. Five years after the surgery, the intramedullary tumor extended to the levels from Th8 to L1 and was partially resected. It showed histologic features similar to those of the first tumor. Two years after the second surgery, the residual spinal cord tumor was found to widely involve the levels from Th5 to L3. Spinal cordectomy was subsequently undertaken and revealed anaplastic glial cells infiltrating diffusely into the spinal cord parenchyma, with prominent subarachnoid spreading and nerve root involvement. Both necrosis and microvascular proliferation were observed. This recurrent tumor was histologically indistinguishable from glioblastoma. Loss of ATRX was noted in the second and third surgical specimens. This is the first histologically proven case of malignant transformation of NF1-associated astrocytoma with ATRX loss during the course.