Enteroviral Encephalitis in a Child With CNS Relapse of Burkitt Leukemia Treated With Rituximab.

A boy with central nervous system relapse of Burkitt leukemia developed fever and neurologic symptoms and cognitive impairment. He had received multi-drug chemotherapy including rituximab. Enterovirus (EV) was detected in cerebrospinal fluid by polymerase chain reaction, and magnetic resonance imaging findings were consistent with viral infection. The patient was treated with intravenous immunoglobulin and within 1 month cleared his EV. Rituximab can cause a profound B-cell deficiency predisposing patients to infections including EV encephalitis. This is the first report of enteroviral encephalitis in a child undergoing treatment for lymphoma with rituximab and suggests the need to watch for this complication of therapy.

Contribution of cerebrospinal fluid sCD19 levels to the detection of CNS lymphoma and its impact on disease outcome.

Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell-associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.

Risk factors for the evaluation of potential central nervous system metastasis in Burkitt's lymphoma: a case study and literature review.

Burkitt's lymphoma (BL) is a malignancy of B lymphocytes. The rapid growth rate and frequent systemic spread result in most patients presenting with advanced disease at diagnosis. Cerebrospinal fluid cytology is the gold standard (with very high accuracy) for diagnosing BL central nervous system (CNS) metastasis; however, the low sensitivity of this method limits its clinical applications. Here, we report a case of BL with CNS metastasis. The levels of vascular endothelial growth factor (VEGF)-A and VEGF-C in the serum and cerebrospinal fluid were used to evaluate the status of BL remission and recurrence. Comparisons were made between VEGF and the other risk factors used in evaluating CNS metastasis. Although not in strict accordance, VEGF levels mirrored the disease course. Therefore, VEGF may reflect the status of BL CNS metastasis. Understanding the role of VEGF in CNS metastasis may help to improve the staging and risk classification of BL as well as the investigation of targeted therapy.

Characteristics of Central Nervous System (CNS) Involvement in Children With Non-Hodgkin's Lymphoma (NHL) and the Diagnostic Value of CSF Flow Cytometry in CNS Positive Disease.

OBJECTIVE: To investigate the characteristics of central nervous system (CNS) involvement in children with non-Hodgkin's lymphoma (NHL) and the value of flow cytometry (FC) in the diagnosis of CNS disease in pediatric NHL. METHODS: The data of 56 newly diagnosed pediatric NHL patients with CNS involvement (CNS+/mass, CNS+/palsy, CNS+/CSF) were analyzed. The proportions and formats of CNS disease in different pathological types were compared. In addition, FC and conventional cytology (CC) of cerebrospinal fluid (CSF) were carried out in 383 newly diagnosed NHL cases. RESULTS: A total of 383 children with NHL were enrolled. Among these patients, 56 (14.6%) were diagnosed with positive CNS involvement (CNS+), 33 had bulky disease (tumor diameter >10 cm), 32 had bone marrow invasion, 32 had lactate dehydrogenase levels >1000 U/L, and 25 had invasion of more than 4 organs at the time of diagnosis. There were 14 patients with T lymphoblastic lymphoma (T-LBL), 9 with B lymphoblastic lymphoma (B-LBL), 26 with Burkitt's lymphoma (BL), and 2 with Epstein-Barr virus-positive diffuse large B cell lymphoma (EBV + DLBCL). Among the 56 CNS+ patients, 35 were CSF-positive (CSF+); there were 2 patients who were CSF+ via CC detection and 35 who were CSF+ via FC detection. The difference between CC and FC was statistically significant (P < 0.01). In the T-LBL group, 14 patients were CNS+/CSF, and in the B-LBL group, 8 were CNS+/mass. In the BL group, 22 patients were CNS+/mass and 15 were CNS+/CSF. In the anaplastic large-cell lymphoma group, 5 patients were CNS+/mass. Nine of the 56 CNS+ patients had events. The 2-year overall survival rate was 87% ± 0.046%, and the 2-year event-free survival rate was 76.2% ± 0.07%. CONCLUSION: CNS+ diagnoses were more common in pediatric NHL patients with bulky disease and/or bone marrow involvement and/or involvement of more than 4 organs at the time of diagnosis, and they were also common in the EBV + DLBCL and BL groups. FC of CSF showed important clinical significance in the diagnosis of CNS disease in pediatric NHL patients, and it can be used to significantly improve the CNS+ detection rate.

Cerebrospinal fluid markers in African Burkitt's lymphoma with central nervous system involvement.

Several cerebrospinal fluid markers were found to be elevated in Burkitt's lymphoma patients with central nervous system (CNS) involvement. Antibody levels to the virus capsid antigen of the Epstein-Barr virus and to the brain cell antigens myelin and cerebroside were elevated during active CNS disease. Immune complexes were present in levels above 100 micrograms/ml in most patients with CNS involvement but tended to be low or negative in patients without CNS disease. Oligoclonal IgG bands were present in 12 of 13 patients with CNS disease and in only 3 of 26 patients with no clinical evidence of disease. None of these markers were present in 6 other tumor patients without CNS disease. The presence of these markers in 12 of 13 patients in whom CNS disease was involved suggests that these markers may be useful in determining the status of the tumor with regard to involvement of the CNS.

Deceptively normal ventricular fluid in lymphomatous meningitis.

The diagnosis of leptomeningeal cancer ultimately depends on the finding of abnormal cerebrospinal fluid with malignant cytologic study results. We report a case of relapsed leptomeningeal lymphomatosis in which ventricular cerebrospinal fluid was entirely normal while lumbar spinal fluid was diagnostically abnormal. To our knowledge, this is the first such reported case, and it highlights the importance of sampling cerebrospinal fluid close to the site of clinical involvement.

Oligoclonal IgG in CSF of patients with African Burkitt's lymphoma.

Oligoclonal IgG bands were detected in CSF from 12 of 13 patients with African Burkitt's lymphoma (BL) who exhibited neurologic signs or symptoms of CNS involvement. Twenty-three of 26 patients free of neurologic involvement with this tumor were found to lack the oligoclonal IgG bands in their CSF. None of six patients with non-BL included in this study had these bands in their CSF. None of six patients with non-BL included in this study had these bands in their CSF samples. These findings suggest that detection of these bands may be a useful adjunct for determining the presence of African BL that invades the CNS.

Analysis of cerebrospinal fluid cells from an american child with Burkitt's Lymphoma.

Tumor cells in the cerebrospinal fluid of an American child with Burkitt's lymphoma are described. The morphology of the cells was demonstrated better by use of the "millipore" technic and hematoxylin and eosin staining than by the Wright-stained smear.

Association of immunophenotype with cerebrospinal fluid involvement in childhood B-lineage acute lymphoblastic leukemia.

The records of 71 pediatric patients who had B-lineage acute lymphoblastic leukemia (ALL) were studied retrospectively to document the correlation between antigenic phenotype of leukemic blasts in bone marrow (BM) and cerebrospinal fluid (CSF) involvement. Immunofluorescence assay for terminal deoxynucleotidyl transferase (TdT-IF) was used to examine specimens of CSF for the presence (CSF+) or absence (CSF-) of leukemic blasts at diagnosis and at various times after the induction of chemotherapy. The results of immunophenotyping of the leukemic blasts in the BM of the CSF+ and CSF patient groups were then compared, and the relative risk ratio and positive predictive value were calculated for each marker. In addition, other possible prognostic factors, such as gender, race and ethnicity, age, and initial leukocyte count were compared between the two groups. Thirty-eight percent of all patients, including those who had cytologically confirmed cases of CNS leukemia, had TdT+ cells in the CSF at diagnosis or during the course of the disease. No differences were observed between the CSF+ and CSF- groups with respect to clinical and demographic factors. However, the cases of CSF+ leukemia had the almost exclusive expression of cytoplasmic immunoglobulin heavy chain (c mu) or surface CD22 (Leu-14), CD23 (B6), and/or IgM markers, which normally characterize the most developmentally mature members of the B-cell series in BM. The expression of any of these antigenic markers at diagnosis appears to identify at least 88% of cases of B-lineage ALL that have or ultimately may have TdT+ cells in CSE The results of this study therefore may have both basic and clinical implications: The former concerns the mechanisms by which these phenotypically defined forms of ALL invade and persist in the CNS; the latter concerns the utility of routine immunophenotyping of BM blasts at diagnosis to assess the biologic predisposition to CNS involvement in individual cases of ALL.

Cerebrospinal fluid neopterin levels in children with central nervous system leukemia.

Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high-grade lymphomas). When meningeal relapse was diagnosed, all patients had CSF neopterin levels higher than mean normal value +2 standard deviations. No significant correlation between the blast count in the CSF and neopterin levels was observed. CSF data before relapse were available in 10 children: the neopterin values at relapse were significantly higher than values observed at diagnosis. In 3 patients, elevated neopterin levels preceded the occurrence of neurologic signs and the detection of blast cells in CSF by 15 to 30 days. In the absence of infection, the rise of CSF neopterin levels in patients with hematologic malignancies indicates an active phase of the disease. This could reflect a cell-mediated immunologic process induced by malignant cells. The measurement of CSF neopterin should be helpful in the monitoring of patients to detect early meningeal relapse.

Burkitt's lymphoma--a correlated light and electron microscopic study on the malignancy in the CSF.

In a sporadic case of primary maxillar Burkitt's lymphoma and secondary spinal epidural dissemination, the massive malignancy in the CSF was investigated by light and electron microscopy. At both levels the CSF tumor cells were strikingly similar, with the undifferentiated lymphoblasts that characterize Burkitt's lymphoma in tissue. However, the starry-sky appearance in the CSF was produced more often by degenerating malignant cells than by histiocytes as classically described in tissue with Burkitt's lymphoma.

The cytodiagnosis of malignant lymphomas and Hodgkin's disease in cerebrospinal, pleural and ascitic fluids.

One hundred twenty-six fluids from 98 patients with malignant lymphomas have been examined cytologically. The overall accuracy was 88 per cent with only one false positive in 126 fluids. False negatives were highest in the cerebrospinal fluid, which may reflect poor exfoliation of malignant lymphoma cells when the leptomeninges are involved. We have found exfoliative cytology to be an accurate method of diagnosing lymphomatous involvement of the leptomeninges, pleura and peritoneum and when a cytologic diagnosis of involvement by lymphoma is made it is almost as accurate as a histologic diagnosis. Nuclear characteristics and selected histochemical methods will allow classification of many types of lymphoma in bytologic preparations.

[Signification of Epstein-Barr virus detection in the cerebrospinal fluid of a patient with human immunodeficiency virus related Burkitt lymphoma]. / Signification de la détection du virus d'Epstein-Barr dans le liquide céphalorachidien d'un patient suivi pour un lymphome de Burkitt lié au virus de l'immunodéficience humaine.

The significance of Epstein-Barr virus detection in the cerebrospinal fluid of patients with Burkitt lymphoma is poorly studied. We report the case of a patient with immunodeficiency associated Burkitt lymphoma in complete remission who presented 5 months after the end of treatment, an isolated optic neuritis. Lumbar puncture found lymphocytic meningitis and the viral load of Epstein-Barr virus was 234,000 copies per milliliter in the cerebrospinal fluid. These symptoms could be explained by Epstein-Barr virus meningoencephalitis but the detection of MYC rearrangements in the cerebrospinal fluid confirms the diagnosis of Burkitt lymphoma cerebral relapse. The detection of the Epstein-Barr virus DNA in the cerebrospinal fluid should be interpreted with caution.

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non-Hodgkin's lymphoma in AIDS patients.

BACKGROUND: Neurological disorders are common in HIV-infected patients. Central nervous system (CNS) lymphoma should always be considered because it is an important cause of morbidity and mortality. OBJECTIVES: To investigate the clinical utility of flow cytometry immunophenotyping (FCI) in diagnosing or discarding leptomeningeal involvement in HIV-infected patients and to compare its sensitivity with that of conventional cytological methods. METHODS: Fifty-six cerebrospinal fluid (CSF) samples from 29 HIV-infected patients were independently evaluated by flow cytometry and cytology. The description of an aberrant immunophenotype was the criterion used to define the malignant nature of any CSF cell population. RESULTS: FCI and cytology gave concordant results for 48 of the 56 CSF samples studied: 37 were negative for malignancy and 11 had evidence of CNS lymphoma. Discordant results were obtained for eight CSF samples, and the accuracy of the FCI findings could be demonstrated for four CSF samples described as positive for malignancy according to the FCI criteria. CONCLUSIONS: A high level of agreement was found between the results obtained using the two methods, but FCI gave at least 25% higher sensitivity than conventional cytomorphological methods for the detection of malignant cells. This advantage suggests that, in case of negative flow cytometry results, disorders other than non-Hodgkin's lymphoma should be strongly considered.

Unusual presentation of a primary spinal Burkitt's lymphoma.

Primary CNS lymphomas are detected with increasing frequency in immunocompetent and immunodeficient persons. Primary involvement of the spinal roots has only rarely been reported. The unusual history is described of a patient with a primary spinal Burkitt's lymphoma initially presenting as an S1 syndrome showing lymphocytic pleocytosis in the CSF, leading to the misdiagnosis of meningoradiculitis. Repeated spinal MRI disclosed a spinal mass lesion and histological and immunohistological examination of the tumour confirmed the diagnosis of spinal Burkitt's lymphoma.

Pregnancy-specific beta 1 glycoprotein (SP1) in the cerebrospinal fluid.

Pregnancy-specific beta 1 glycoprotein (SP1) was assayed by Particle Counting Assay in the cerebrospinal fluid (CSF) from 26 non-neurological patients, from 190 patients with various neurological disorders and from 84 patients with malignant hemopathies. With a sensitivity limit of 0.5 microgram/l, SP1 was undetectable in normal CSF. High levels were observed in CSF from one pregnant woman with herpetic encephalitis and from another woman with post-puerperal thrombophlebitis as a result of high serum concentrations and leakage of the blood-brain barrier. SP1 was detected at low levels in the CSF from 1 patient out of 5 with Creutzfeldt-Jakob disease and from a patient with Behçet's disease. Seven patients out of 84 with malignant hemopathies presented cerebral involvement; 3 of them had detectable SP1. However, SP1 was also detected in the CSF of 2 patients in apparently complete remission. The determination of SP1 in CSF appears to be of limited value in the diagnosis of neurological disorders and in the early detection of a cerebral localization of malignant hemopathies.