John J. Kepes

Twelve cases of a distinctive form of supratentorial astrocytoma occurring in young subjects (ages 7 to 25) are reported. The tumors were superficial and involved the leptomeninges extensively. The tumor cells display marked pleomorphism, including bizarre giant cells and a number of mitotic figures, but no necrosis. Many contain large amounts of lipid in their cytoplasm and are surrounded by reticulin fibers, thus simulating a mesenchymal tumor. For these reasons, some examples of this tumor have been previously interpreted to represent meningocerebral fibrous xanthomas. Immunoperoxidase technique performed in nine of the twelve cases has, however, established the presence of glial fibrillary acidic protein in the tumor cells, which are therefore considered to be astrocytic. By electron microscopy many tumor cells are surrounded by basal laminae, accounting for the abundant reticulin network demonstrable in silver preparations. Since subpial astrocytes are known to be partly covered by a basal lamina, it is likely that they are the cells of origin for this neoplasm. In contrast to its pleomorphic cytology, the biological behavior of this tumor appears to be relatively favorable, and long survival times (up to 25 years) have been recorded in some cases. (These tumors are distinct from intracranial fibrous xanthomas of mesenchymal derivation. Cells of the latter are negative on GFAP stain.)

Thirty-one patients with large, focal cerebral demyelinating lesions are reported. Twenty-four patients had solitary lesions and 7 had multiple foci, the latter apparently of identical age. The lesions presented clinically and radiologically as brain tumors (gliomas or metastases) or as multiple cysts. Six patients were older than 57 years (2 in their 70s) at the onset of their symptoms. The demyelinating nature of the lesions was established through biopsy in each patient and all improved significantly after corticosteroid therapy. Three patients developed additional lesions during the follow-up periods ranging from 9 months to 12 years consistent with the course of multiple sclerosis. Twenty-eight patients did not develop additional lesions. These included 6 patients with multiple lesions at the onset. In 1 of the patients, the first symptoms developed 10 days after receiving vaccination against influenza. Two patients had concomitant malignancy (chronic monomyelogenous leukemia and retroperitoneal seminoma respectively) and 1 patient developed immunoblastic sarcoma in the opposite hemisphere after biopsy diagnosis and steroid treatment of her demyelinating lesion. Tumor-like masses of demyelination may occupy an intermediate position between multiple sclerosis and postinfectious/postvaccination encephalitis. The clinical course (history of vaccination in one instance, acute onset, good response to corticosteroids, no clinical or radiological evidence of new lesions in the great majority of patients) favored postinfectious/postvaccination encephalitis. Lesion size however greatly exceeded that of the small foci of perivenous demyelination seen in typical postinfectious/postvaccination encephalitis and tended to present as space-occupying masses.

Seven young patients ranging in age from 8 to 19 years had surgically removed meningeal neoplasms with a peculiar myxoid-chordoid pattern. The tumors were surrounded by massive polyclonal lymphoplasmacellular infiltrates with follicles and germinal centers. The patients preoperatively manifested iron-resistant hypochromic microcytic anemia, and one of them had dysgammaglobulinemia and stunted growth. After the masses were removed, the blood picture of the patients normalized, and the adolescent with retarded somatic development resumed normal growth, but two patients developed local recurrence with identical histology and again became anemic. It appears that the peritumoral lymphoplasmacellular infiltrates, which in these instances may be regarded as reactive rather than primary cell proliferations, nevertheless brought about the type of systemic manifestations known as the Castleman syndrome, characteristically seen in patients with angiofollicular lymphoid hyperplasia (hamartoma) of soft tissues, or Castleman's tumor. In one of our patients the inflammatory infiltrate extended far into the surroundings of the meningioma, resulting in the erroneous initial diagnosis of "encephalitis" from a needle biopsy of the brain near the tumor.

Meningiomas and their principal cells of origin, the arachnoidal "cap" cells are unique in their morphology with multiple and sometimes seemingly contradictory features related to their origins and basic character. Some meningiomas express mesenchymal features either in histologic pattern (fibroblastic, lipo-myxochondro-osteoblastic differentiation), participation in other disease processes, e.g. taking part in the formation of rheumatoid nodules, or in storage phenomena shared with other mesenchymal cells of the body. At the same time they may display epithelial features, such as well-formed desmosomes ultrastructurally, papillary formations and intracellular lumina in cells that stain positively for various cell markers usually considered to characterize epithelial cells. Histologic similarities of meningiomas to various gliomas, schwannomas, neuroblastomas, fibrous histiocytomas, myxomas, chordomas, metastatic carcinomas, and in the cases of meningiomas with marked inflammatory infiltrates, to benign or malignant lymphoproliferative disorders involving the meninges may pose serious diagnostic problems. The localization and resectability of meningiomas are important factors related to long-term prognosis. Of the histologic features hemangiopericytomatous pattern, papillary formations, high cellularity (focal or diffuse) and invasion of the brain appear to correlate with potentially aggressive behavior, whereas cytologically aneuploidia, large number of mitoses, prominent nucleoli and cell necrosis suggest a guarded prognosis. However, some meningiomas with no detectable histologic features of malignancy may nevertheless metastasize to distant sites.