Neurofibromatosis type 2 (NF2) protein, also known as merlin or schwannomin, is a tumor suppressor, and NF2 is mutated in most schwannomas and meningiomas. Although these tumors are dependent on NF2, some lack detectable NF2 mutations, which indicates that alternative mechanisms exist for inactivating merlin. Here, we demonstrate cleavage of merlin by the ubiquitous protease calpain and considerable activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway.

The authors review 30 documented cases of intracranial and orbital cavernous angiomas treated at their institution between 1965 and 1984. The diagnosis was based on computerized tomography (CT) or surgery; three patients were treated in the pre-CT era (1965 to 1976) and 27 since the advent of CT. The number of cases diagnosed preoperatively markedly increased after the introduction of CT, and 22 cases were verified histopathologically at surgery. Six cases were in children (aged 2 months to 17 years) and 24 in adults (aged 19 to 73 years). There was no significant sex difference (male:female ratio was 14:16). Nineteen lesions were intraparenchymal, five were intraventricular, three were in the middle fossa, two were intraorbital, and one originated from the tentorium. Symptoms varied according to the site of the lesion; hemorrhage occurred in 11 cases. Calcifications were seen on CT scans in all cases, but on plain skull films in only two. Angiography revealed hypovascular masses in all cases excluding those with lesions in the middle fossa; in two cases, tumor stain could be detected only with prolonged-injection angiography. Radionuclide brain scanning showed a dense hot area in eight of 19 patients. Recent experience has shown that magnetic resonance imaging clarified anatomic relationships that were obscure on CT. The overall outcome was favorable except for one patient who died in the postoperative period. The clinical results in this series are summarized and some diagnostic and therapeutic problems are discussed.

A rare case of primary spinal intramedullary malignant melanoma at the T6 level in a 31-year-old man is presented. The tumor was partially removed, and neuroaxis irradiation up to 50 Gy was then administered. Subsequently, systemic interferon beta (specific activity, 2.0 × 108 IU/mg protein) therapy (total dose, 2.2 × 107units) was begun. At the completion of these therapies, immunohistochemical analysis with monoclonal antibodies against melanoma-associated antigens confirmed the presence of melanoma cells in the cerebrospinal fluid (CSF). Chemotherapy with intrathecal administration of dacarbazine (dimethyltriazenoimidazole carboxamide, DTIC) was then initiated, to avoid the dissemination of tumor cells by the CSF. Periodic cytological examination of CSF for melanoma cells revealed a marked reduction in the number of tumor cells. Pharmacokinetic study showed that the disappearance of DTIC from the CSF was biphasic, with an initial half-life of 30 minutes and a terminal half-life of 5 hours. Follow-up examination by MRI 1 year after the operation did not disclose any significant increase in size of the residual tumor. Neither recurrence nor metastasis was observed. The pertinent literature on spinal cord melanoma is reviewed, and the usefulness of MRI and intrathecal chemotherapy with DTIC is discussed.

The findings show that PI3-K is a possible target for therapy in patients with gliomas, and PI3-K inhibitors in combination with chemotherapeutic agents could be potent therapeutic modalities for patients with malignant gliomas.

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