The Malformative Central Nervous System Lesions in the Central and Peripheral Forms of Neurofibromatosis. A Neuropathological Study of 22 Cases

The neuropathological features of 22 autopsied cases of NF have been reviewed, with special reference to the malformative and proliferative lesions implicating the intracranial and intraspinal neural structures. Eleven cases represented examples of the central form of the disease, and 11 examples of the peripheral form. The central form is defined by the association and multiplicity of cranial and spinal meningeal, nerve-sheath, and glial neoplasms (astrocytomas and ependymomas). Bilateral acoustic schwannomas are a frequent, but not invariable, component of the disease. Central NF is also characterized by the very frequent incidence (9 out of 11 cases) of distinctive malformative CNS lesions, which included intramedullary and perivascular schwannosis, meningioangiomatosis, discrete ependymal ectopias, atypical glial cell nests in the grey matter, and, less frequently, syringomyelia. Many of these hamartomatous changes were closely associated topographically with florid neoplastic lesions. Five of the 11 cases of peripheral NF showed involvement of the CNS by cellular proliferative changes that included subependymal gliofibrillary nodules in 3 cases (causing aqueduct stenosis in 2, with resulting hydrocephalus in 1); hyperplastic meningioencephalic gliosis involving the pons and the cerebellum in 1 case; and micronodular capillary and arteriolar proliferations typical of the vascular form of NF in 1 case. Whereas some of the glial proliferations are probably hamartomatous in nature, others may represent an abnormal productive neuroglial response to adjacent pathological conditions, such as antecedent cerebral hemorrhage or infarct, known to stimulate a proliferative gliosis. Such a response may exhibit morphological features that are indistinguishable from those of an astrocytoma, including leptomeningeal and perivascular invasion. The incidence of proliferative CNS lesions in both the central and the peripheral form of NF indicates that the spectrum of tissues implicated extends beyond those derived solely from the neural crest.