Extraneural metastasizing ependymoma of the spinal cord.
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This paper reports a case of the rare entity of an extraneural metastasizing ependymoma of the spinal cord. The tumor which arose in the conus medullaris and in the cauda equina was first diagnosed in 1956 when a thoracolumbar myeloresection was performed. At autopsy, 40 years after the primary diagnosis, a massive local tumor recurrence with extraneural metastases in the lungs, the pleura, the liver, and the thoracal and abdominal lymph nodes were found. Immunohistochemical stains of the extraneural metastases showed a strong cytoplasmatic expression of glial fibrillary acidic protein (GFAP). Neither the primary tumor nor its metastases showed any of the conventional morphological criteria of malignancy. Reviewing the literature we discuss the possible mechanism of extraneural tumor spread and the incidence of metastases with regard to the tumor type. (+info)
Recurrent spinal epidural metastases: a prospective study with a complete follow up.
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OBJECTIVES: Prospective studies with a complete follow up in patients with spinal epidural metastases (SEM) are rare, so little is known of the incidence and relevance of recurrent spinal epidural metastases (RSEM). This prospective study was undertaken as a part of a previously started and extended prospective study to determine the occurrence and details of RSEM. METHODS: Patients with SEM of various primary malignancies were followed up until death. The diagnosis was confirmed after neurological examination by imaging studies visualising not only the clinically suspected level, but also as much of the spinal canal as possible. RESULTS: Recurrent spinal epidural metastases (RSEM) occurred in 21 of the 103 patients (20%) after a median interval of 7 months and, after treatment, a second recurrence occurred in 11 patients (11%), a third recurrence in two patients (2%), and a sixth recurrence in one patient (1%). RSEM developed about as often at the initial level (55%) as at a different level (45%), did not occur more often in patients with initially multiple SEM, but, not surprisingly, occurred much more often in patients with longer survival. About one half of the patients surviving 2 years, and nearly all patients surviving 3 years or longer developed RSEM. Ambulatory state could be preserved in most patients, even after their second recurrence. CONCLUSION: RSEM are common and even several episodes of RSEM in the same patient are not rare. Patients with SEM who survive long enough have a high risk of RSEM and prompt treatment of RSEM to maintain the ambulatory state of the patient is valuable. (+info)
Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society.
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Methotrexate-albumin conjugate (MTX-HSA) is a novel human albumin-based prodrug conjugate of methotrexate (MTX). A low MTX loading rate provided optimal tumor targeting and therapeutic efficacy during preclinical testing. The objectives of this first Phase I study of MTX-HSA were to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) in a weekly regimen. Seventeen cancer patients who were no longer amenable to standard treatment were enrolled and were evaluable for DLT. Up to eight injections were performed in weekly intervals. Dose escalation was as follows: 20, 40, 50, and then 60 mg/m2 MTX-HSA (based on the amount of MTX bound to albumin). Additional MTX-HSA courses were feasible in case of tumor response. DLT (mainly stomatitis, Common Toxicity Criteria grade 3) occurred, beginning at the 50 mg/m2 dose level after repeated administrations; in one case, thrombocytopenia was dose-limiting. Two events of DLT occurred at the 60 mg/m2 dose level within the first two administrations. Mild anemia, transaminitis, and one case of skin toxicity were found. No significant leukopenia, nausea, renal toxicity, or other toxicities were observed. MTX-HSA was well tolerated. Drug accumulation occurred on the weekly schedule. The half-life of the drug was estimated to be up to 3 weeks. Tumor responses were seen in three patients: (a) a partial response was seen in one patient with renal cell carcinoma (response duration, 30 months, ongoing); (b) a minor response was seen in one patient with pleural mesothelioma (response duration, 31 months, ongoing); and (c) a minor response was seen in one patient with renal cell carcinoma (response duration, 14 months until progression). Poststudy treatment was administered at 2-4-week intervals. No signs of toxicity or drug accumulation were seen. Altered pharmacological properties of MTX-HSA such as plasma half-life, tumor targeting, or intracellular metabolism might have contributed to these responses. The MTD for weekly administration was 4 x 50 mg/m2 MTX-HSA during short-term treatment. A regimen with MTX-HSA injections of 50 mg/m2 every 2 weeks was recommended for a further clinical Phase I study. (+info)
Diffusion tensor MR imaging and comparative histology of glioma engrafted in the rat spinal cord.
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MR imaging using contrast material derived from the diffusion of tissue water was tested for its ability to provide a nondestructive histologic analysis of tumor morphology. An apparent diffusion tensor MR image of a glioma engrafted within a rat spinal cord was generated in which fiber orientation in three dimensions was displayed in color. This imaging method clearly separated tumor from host white and gray matter and corresponded well with conventional histologic microscopy. (+info)
Second lung adenocarcinoma after combination chemotherapy in two patients with primary non-Hodgkin's lymphoma.
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We report a rare complication of a secondary malignant solid tumor in two patients with non-Hodgkin's malignant lymphoma who developed lung adenocarcinoma after treatments with combination chemotherapies. The first was a case of primary malignant lymphoma of the cervical spinal cord which had been previously treated with radiation to the spinal lesion and combination chemotherapies and entered complete remission. The patient was further treated for relapse with autologous bone marrow transplantation preconditioned with high-dose chemotherapy. Lung adenocarcinoma developed 5.5 years after the initial diagnosis. The second case of malignant lymphoma of lymph nodes did not respond to conventional combination chemotherapies and did not enter remission. Lung adenocarcinoma developed 1 year after the initial diagnosis. The two patients died of lung carcinoma. The clinical profiles of these cases are presented and the causal relationship of primary malignant neoplasms to the second malignant neoplasms is discussed. (+info)
Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas.
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Ependymal tumors are heterogeneous with regard to morphology, localization, age at first clinical manifestation, and prognosis. Several molecular alterations have been reported in these tumors, including allelic losses on chromosomes 10, 17, and 22 and mutations in the NF2 gene. However, in contrast to astrocytic gliomas, no consistent molecular alterations have been associated with distinct types of ependymal tumors. To evaluate whether morphological subsets of ependymomas are characterized by specific genetic lesions, we analyzed a series of 62 ependymal tumors, including myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic ependymomas, for allelic losses on chromosome arms 10q and 22q and mutations in the PTEN and NF2 genes. Allelic losses on 10q and 22q were detected in 5 of 56 and 12 of 54 tumors, respectively. Six ependymomas carried somatic NF2 mutations, whereas no mutations were detected in the PTEN gene. All six of the NF2 mutations occurred in ependymomas of WHO grade II and were exclusively observed in tumors with a spinal localization (P = 0.0063). These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis. Furthermore, our data suggest that the more favorable clinical course of spinal ependymomas may relate to a distinct pattern of genetic alterations different from that of intracerebral ependymomas. (+info)
Association of lower cranial nerve schwannoma with spinal ependymoma in ? NF2.
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A 15 year old male, who had earlier been operated for intraspinal intramedullary ependymoma, subsequently developed a right cerebello pontine (CP) angle mass. A diagnosis of right CP angle ependymoma was considered, in view of established histology of previously operated spinal lesion. Histopathological examination of the well defined extra-axial mass, which was attached with ninth cranial nerve, however revealed a schwannoma. A diagnosis of Neurofibromatosis-2 (NF2) is strongly suspected, because of well established fact, that the spinal ependymomas may have association with lower cranial nerve schwannomas in NF2. Cranial and spinal MRI screening for early diagnosis of associated, asymptomatic lesions, in suspected cases of NF2, particularly in children, is recommended. (+info)
Management of intramedullary spinal cord tumours: review of 68 patients.
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68 consecutive patients admitted with intramedullary spinal cord tumours and operated at Vellore during a six year period from January 1990 are discussed. 41 tumours were radically resected, 11 partially excised while 14 had only a biopsy. Radiation therapy was advised post operatively to those patients for whom a partial excision or biopsy was done. There was no postoperative mortality. Two patients developed wound infection and one developed postoperative hydrocephalus. Postoperative clinical assessment between four to eight weeks after surgery showed that 25 out of 68 patients improved, 29 remained unchanged, while 14 had worsening of deficits. Immediate post operative assessment, however, was less encouraging. Evaluation of these patients was done using a functional scoring system and Karnofsky rating. The follow up period ranged from 2 weeks to 64 months after discharge from hospital with a mean of 14.6 months. The indicators of radical excision were good tumour-cord interface, cranially located tumours, presence of syringomyelia and histology of ependymoma. Two patients had recurrence of tumour. (+info)