Response of Leptomeningeal Dissemination of Anaplastic Glioma to Temozolomide: Experience of Two Cases

Abstract

The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been increasing. LMD can be observed at the time of initial presentation or the time of recurrence. As a result of both rarity and unusual presentation, a standard therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis for systemic solid cancers, a relatively prolonged survival is observed in some patients with LMD of anaplastic gliomas. Treatment modalities include whole craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and systemic chemotherapy. In some cases, response to temozolomide (TMZ), with or without combined radiation has been reported. Here, we report two cases of LMD of an anaplastic glioma. In one case LMD presented at the time of diagnosis, and in the other at the time of recurrence after radiation. CSF cytology was positive in both cases, and persisted in spite of intrathecal methotrexate chemotherapy. Later, TMZ was prescribed for progressing brain parenchymal lesions, and both radiological and cytological responses were obtained after oral TMZ treatment.

Keywords: Cerebrospinal fluid; Drug effect; Leptomeningeal carcinomatosis; Malignant glioma; Temozolomide.

Fig. 1. Radiologic findings of Case 1. Initial axial T2-weighted magnetic resonance findings of a 54-year-old male patient diagnosed with anaplastic oligoastrocytoma (A and B), and sagittal and coronal T1-weighted images enhanced with gadolinium after the first craniotomy (C and D). Periventricular enhancement occurred after ifosphamide, carboplatin, and etoposide chemotherapy and intrathecal methotrexate (E and F). After treatment with temozolomide, leptomeningeal enhancement disappeared (G and H), and the T2-weighted signal intensity of the cerebellar lesion decreased (I).

Fig. 2. Pathologic findings of Case 1. Increased cellularity and branching capillary networks resembling that of oligodendroglioma (A, original magnification, ×200; hematoxylin and eosin staining) and intermingled oligodendroglial cells having round nuclei and clear cytoplasm and astrocytic cells of elongated nuclei (B, original magnification, ×400; hematoxylin and eosin staining).

Fig. 3. Radiologic findings of Case 2. A second illustrative case of a 38-year-old female patient with a mesencephalic T2 high signal intensity lesion with spotty enhancement (A and B). After radiation, the extent of the lesion decreased (C), but metastasis developed 3 years later (D). Multiple enhancing nodules around the periventricular area occurred during ventriculolumbar perfusion chemotherapy (F and G). After six cycles of TMZ, imaging reveals resolution of the enhancing lesion (H), but another solitary lesion at the cerebellopontine angle appeared after 12 cycles of TMZ (I). TMZ, temozolomide.

Fig. 4. Pathologic findings of Case 2. High cellularity with closely packed polygonal cells of clear cytoplasm and branching capillary networks with tumor infiltration to surrounding granular layer of the cerebellum (A, original magnification, ×200; hematoxylin and eosin staining), and abundant clear cytoplasm and centrally located round to oval nuclei with nuclear pleomorphism (B, original magnification, ×400; hematoxylin and eosin staining).