Isolated central nervous system metastasis from ovarian carcinoma: a case report

Ovarian adenocarcinoma usually disseminates and recurs the abdominal cavity. The detection of central nervous system metastases is rare. In this report we describe a case of intracranial recurrence that developed during a complete local surgical and pathological response and was treated radically with surgery followed by radiation.     

Central nervous system metastases in epithelial ovarian carcinoma

Five new cases of central nervous system (CNS) metastases from epithelial ovarian cancer are described. They are discovered among 255 patients treated at University of California, Los Angeles (UCLA) Medical Center, giving an incidence of CNS metastases of 1.96%. All five patients had intraparenchymal brain metastases. It seems likely that the incidence of CNS involvement is increasing in this disease, consonant with improvement of local tumor control and prolonged overall survival. The median duration from the diagnosis of ovarian cancer to the diagnosis of CNS metastases was 25 months (range, 10-126 months). Median survival after diagnosis was 1.3 months (range, 1-10 months). Therapeutic options are discussed, as are possible mechanisms for the occurrence of these metastases.     

Involvement of central nervous system in prolymphocytoid transformation of chronic lymphocytic leukemia

We report a rare case of involvement of the central nervous system (CNS) by chronic lymphocytic leukemia (CLL). A 68-year-old man with prolymphocytic variant of B-CLL (CLL/PLL), develops CNS involvement with headache and vomiting. Computed tomography of the head showed no abnormalities. The cerebrospinal fluid (CSF) revealed numerous lymphocytoid cells of prolymphocytic appearance consistent with findings on the peripheral blood smear. Immunophenotypic analysis demonstrated that the leukemic B cells were positive for CD19, CD20, and HLA-DR, but CD5 was difficult to detect. The patient was treated with intrathecal methotrexate, cytarabine, and hydrocortisone and had improvement in symptoms and CSF findings. Although CNS involvement is an unusual manifestation in CLL, one should be aware of the possibility of this complication in cases presenting with neurological symptoms.     

Central nervous system metastases in patients with ovarian carcinoma

BACKGROUND: Central nervous system (CNS) involvement by ovarian carcinomais rare. PATIENTS AND METHODS: From September 1982 to September 1994, 23 patients with CNSmetastases from ovarian carcinoma were observed in our institution. RESULTS: Their median age at the time of CNS metastasis diagnosis was59 years, and the median interval between diagnosis of ovariancancer and documentation of the metastasis was 35 months. Themost common symptoms related to CNS involvement were motor weakness,headache, seizures, dizziness and visual disturbances. One patienthad meningeal carcinomatosis; 22 had parenchyma] lesions (18cerebral and 4 cerebellar). Nine patients had a single CNS lesion,and 13 had multiple metastatic sites. CNS was the only siteof disease in 9 patients, while 8 had concomitant extra-peritonealdissemination. The median survival (MS) from diagnosis of cerebralmetastases for the entire series was five months. Four patientswere not treated (MS 3 months); 14 received radiotherapy (MS5.5 months), and five underwent surgical resection of solitarymetastases followed by radiotherapy (MS 17 months). Number ofCNS lesions, extent of the disease at the time of CNS metastasisand treatment were the only factors which significantly affectedsurvival. CONCLUSIONS: The prognosis of patients with CNS metastasis from ovarian carcinomaappears poor. However, early diagnosis followed by multimodaltreatment may result in significant palliation and improve overallsurvival in a selected group of patients. central nervous system metastasis, ovarian carcinoma     

Haemangiopericytoma of the central nervous system

The records of four patients presenting with a histological diagnosis of haemangiopericytoma of the central nervous system, in Auckland, New Zealand, between 1970 and 1990 were reviewed retrospectively, with the aim of determining the natural history of the disease and response to various treatment modalities. Three out of the four patients reviewed presented with primary cerebral disease and the fourth with a primary spinal cord tumour. All three cerebral primary patients were initially treated with local surgical excision. All three patients received radical radiotherapy following local recurrence. The first two patients remained disease-free locally although one patient developed a solitary liver metastasis 5 years after radiotherapy. The third patient was referred with multiple cerebral metastases and failed to respond to radiotherapy. The patient with the primary lesion in the spinal cord was treated with local excision followed by postoperative radiotherapy and remains disease-free 17 years after treatment. One patient failed to respond to chemotherapy, prescribed to treat a local recurrence adjacent to the previous radiotherapy field. This was successfully excised subsequently. The patient presenting with multiple cerebral metastases was the only patient to die of this disease. Results suggest that local recurrence is avoidable with adequate wide excision of the primary tumour followed by local radical radiotherapy. The role of chemotherapy remains controversial and no conclusion could be drawn regarding the role of palliative radiotherapy from this study. Active treatment and long-term follow-up are necessary because of the relative aggressiveness of this disease and the propensity for late relapses.     

Carcinogenesis and the central nervous system

Wistar rats were injected with the carcinogen 3-MC. The effect of psychoactive drugs on tumor-bearing rats was examined with respect to tumor growth, survival time, and remissions. CNS drugs were given both prophylactically and therapeutically. Psychopharmaceuticals like piracetam and pyrithioxin as well as catecholamine-agonists like imipramine had a definite antineoplastic effect. This effect was increased when combined with other CNS drugs and, in particular, the combination of piracetam with chemotherapeutic agents resulted in a high rate of remission and reduced the toxicity of chemotherapy. Surgical removal of tumors and subsequent treatment with CNS drugs led to a high rate of cure without metastasis. After tumor appearance, we found cerebral neuropathological changes as described in the paraneoplastic syndrome. The EEGs of 3-MC-injected rats showed early pathognomic changes in frequency and amplitude. Similar changes were found in animals with transplantation tumors (Walker carcinoma and Jensen sarcoma). The EEG pattern was normalized after surgical removal of Jensen sarcoma and treatment with piracetam and pyrithioxin. These EEG changes might have occurred as a result of transmitter metabolism; ie, carcinogenesis of both induced tumors and transplanted tumors was accompanied by an increase of GABA content in hypothalamus and hippocampus and a reduced concentration of monoamines or their metabolites in hypothalamus and caudate nucleus. Long-term treatment with piracetam or imipramine again arrested all these changes. More recently, we achieved good results with the combination of CNS drugs and cAMP agonists. We therefore conclude that carcinogenesis interferes with the metabolism or availability of cyclic nucleotides and transmitters that regulate their level. CNS drugs may effect a new balance resulting in tumor suppression.     

Radiation response of the central nervous system

This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathognomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gy in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales.     

Glioneuronal tumors of the central nervous system

Advances in the immunohistochemical detection of neuron-specific and neuronal-associated antigens have resulted in the discovery of neuronal elements in certain primary human brain tumors. The results have been not only to expand what neuropathologists commonly recognize as gangliogliomas, including the tumors now known as glioneurocytic tumor with neuropil rosettes and papillary ganglioneuroma, but also to expand the spectrum of tumor types to now include tumors such as central neurocytoma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile ganglioglioma. These discoveries have helped us to better understand the biology of these tumors and to refine our classification of them. Distinctions among these tumors include sites of predilection, such as the temporal lobe with the dysembryoplastic neuroepithelial tumors, and a spectrum of clinical aggressiveness that spans indolent “quasihamartomatous” lesions, such as the dysembryoplastic neuroepithelial tumor, to high-grade, highly aggressive tumors, such as the supratentorial primitive neuroectodermal tumor (World Health Organization Grade IV). Many of these tumors also commonly exhibit a glial component, as determined by both their histologic appearance and their immunoreactivity for glial fibrillary acidic protein. This review covers these recently described lesions, including the desmoplastic infantile ganglioglioma, the dysembryoplastic neuroepithelial tumor, the papillary glioneuronal tumor, the glioneuronal tumor with neuropil rosettes, and the mixed glioblastoma-cerebral neuroblastoma (supratentorial primitive neuroectodermal tumor), as well as the known tumors, ganglioglioma, medulloepithelioma, and medulloblastoma. For pathologists confronted by this growing array of tumors and subtypes, it is appropriate to focus on them and understand the differential diagnosis to be considered when confronted by them.     

Primary sarcomas of the central nervous system

The medical files of 14 patients with primary brain and spine sarcomas were retrospectively reviewed. Ten patients had primary brain sarcomas and 4 primary spinal sarcomas. The tumors probably originated in the brain substance or blood vessels, in the meninges or in the inner aspect of the skull. The spinal tumors originated in the nerve roots of the cauda equina and in the spinal substance or blood vessels. The most common type was angiosarcoma. Removal of the brain tumors was performed in 95% of the patients. Radiotherapy was delivered to 6 patients with brain sarcomas and to all patients with primary spinal sarcomas. Metastatic disease to the lung or pleural effusion was evident in 2 patients who underwent total removal of their tumors followed by radiation therapy.     

Primary lymphoma of the central nervous system

Primary lymphoma of the central nervous system (CNS) represents a pathology that is no longer considered rare, also in the light of its high correlation with the human immunodeficiency virus (HIV) syndrome reported recently. Often the correct diagnosis of the disease is difficult to reach, owing to the wide spectrum of non-lymphoma pathologies from which it should be differentiated and the invasiveness of some diagnostic techniques. The biologic aggressiveness of the neoplasm often makes a combined radio-chemotherapeutic approach necessary. In contrast, surgical resection does not seem to provide any significant benefit. The clinical experience reported here, together with a review of the most recent literature, lead the authors to suggest the opportunity of treating primary lymphoma of the CNS with the most active and modern chemotherapeutic protocols in association with traditional treatments to obtain an improvement in overall survival.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma (NHL) that is restricted entirely to the brain, leptomeninges, eyes, and rarely the spinal cord. It typically presents with focal neurologic symptoms and is characterized by diffuse infiltration of the brain. Corticosteroids are useful for symptomatic treatment but can interfere with definitive pathological diagnosis. PCNSL is radiosensitive and responds to whole-brain radiotherapy. The use of preirradiation high-dose methotrexate-based regimens has significantly improved response rates and patient survival. Longer survival, however, is often marred by devastating neurotoxicity to which the elderly are particularly susceptible. Newer regimens aim to minimize such toxicity while maintaining the survival benefit of combined modality treatment.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma is an aggressive lymphoma with a molecular biology and genetic profile that appears to be distinct from other types of diffuse large B-cell lymphoma. The median survival after whole brain radiotherapy alone is poor, but is significantly improved after high-dose methotrexate-based combination chemotherapy. The rarity of primary central nervous system lymphoma means that randomised studies have proved challenging, particularly as many patients are elderly and more susceptible to the toxic effects associated with these treatments. Promising treatment strategies are emerging and, wherever possible, patients should be treated within clinical trials. Quality of life and neurocognitive data should be collected prospectively to assess the effect of the disease and treatment.     

原发性中枢神经系统淋巴瘤

原发性中枢神经系统淋巴瘤(PCNSL)是一少见的高度恶性非霍奇金淋巴瘤,其在人免疫缺陷病毒感染人群中的发病率显著高于正常人群.该病病理上为广泛浸润整个脑实质、脊髓及软脑膜等多个部位的弥漫性病变.PCNSL的发病机制不明.大剂量甲氨喋呤为主的联合化疗、放疗结合甲氨喋呤鞘内注射能明显改善其疗效及生存率.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin’s lymphoma that is increasing in incidence. Methotrexate-based chemotherapy in combination with whole-brain radiotherapy (WBRT) has dramatically improved the outcome of patients. However, treatmentrelated neurotoxicity is a significant complication, especially after radiotherapy in the elderly. Despite advances in therapy, several important questions remain regarding optimal methotrexate dose, dosing frequency, adjunct chemotherapy, and the impact of deferring WBRT. Advances in biologic therapy and strategies to intensify the delivery of chemotherapy may help to limit the use of radiotherapy, thus lessening potential neurotoxicity. Studies looking at oncogenic proteins as potential prognostic markers for PCNSL may help us to develop risk-adapted therapies.     

Primary central nervous system lymphomas

Opinion statement Primary central nervous system lymphoma (PCNSL) is widely regarded as one of the primary brain tumors most amenable to treatment. Although whole brain radiotherapy was the cornerstone of therapy for decades, recent work clearly indicates that chemotherapy has become the primary focus of treatment for this disease. The initial treatment of PCNSL for all patients, including the elderly, should be chemotherapy using a high-dose methotrexate-based regimen. Although cranial irradiation has often been combined with methotrexate, the unacceptably high incidence of late neurotoxicity, particularly in older patients, has caused many to eliminate radiotherapy, especially in those older than age 60 years. Emerging data support the validity of this approach, and the development of more efficacious chemotherapeutic regimens has been the focus of recent research.