Clear cell meningioma. A clinicopathologic study of a potentially aggressive variant of meningioma

Since clear cell meningioma has only recently been recognized as a morphologic entity, its pathobiology has not been studied. Fourteen examples occurring in seven females and six males, ages 9 to 82 years (mean 29 years), were examined; one was associated with type 2 neurofibromatosis. Of these cases, seven (50%) were spinal-intradural (six lumbar, one thoracic), three (21%) arose in the posterior fossa (cerebellopontine angle), three (21%) were supratentorial, and one (7%) was centered upon the foramen magnum. In one case (8%), two tumors were considered to be independent primaries. One tumor (8%) appeared to show no dural attachment. Thirteen tumors were subject to complete study. All were composed of sheets of clear, glycogen-rich, polygonal cells forming only a few vague whorls. Hyalinization, both stromal and perivascular, was often extensive. Mitoses were rare in primary tumors. Immunohistochemistry showed vimentin and epithelial membrane antigen staining to be reactive in 100%. Stains for S-100 protein and CAM 5.2 were negative. Progesterone and estrogen receptor staining was observed in 77% and 0%, respectively. Ultrastructural study showed abundant cytoplasmic glycogen, a few cytoplasmic lumina, intermediate filaments, interdigitation of cell membranes, and desmosomal junctions. The means, medians, and ranges of proliferating cell nuclear antigen (PCNA) and MIB-1 antigen labeling indices for nonrecurring and recurring tumors were 10.4%, 8.8%, 0.8-23.4% and 11%, 1.4%, 0.1-50.3%, as compared with 7.4%, 6.7%, 2.9-17.2% and 13.3%, 13.4%, 3.3-25.7%, respectively. Twelve successful DNA ploidy studies showed that 11 tumors (85%) were diploid and one was tetraploid; percentage S-phase determinations varied from 4 to 9% (mean 6.0%). Recurrence was noted in eight patients (61%) (five of whom had multiple recurrences); there was local discontinuous spread in two cases (15%) and widespread cranial to spinal metastasis in one case (8%). Three patients (23%) are dead of disease. In summary, clear cell meningiomas are morphologically unique, show no sex predilection, affect primarily the lumbar region and cerebellopontine angle, and despite their benign appearance, may be inordinately aggressive, particularly intracranial examples. No close association was noted between recurrence or clinical outcome and such factors as mitotic activity, PCNA proliferation indices, percent S-phase determination, or DNA ploidy status. In contrast, MIB-1 proliferation indices were appreciably higher among recurring tumors.