Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis

Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2-3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2-12%, a p53 LI of 2-8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2-3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma.