Gliomatosis cerebri: report of 3 cases.

Gliomatosis cerebri is an uncommon glial neoplasm that is exceedingly rare in children and difficult to diagnose. The authors describe the presentation and diagnosis of GC in 3 children ages 12, 14, and 16 years. These children exhibited signs and symptoms of increased intracranial pressure as well as other vague or site specific neurological signs. Because clinical presentation, CSF analysis, and neuroimaging were nonspecific, a stereotactic biopsy to obtain tissue for pathological review was ultimately necessary to confirm the diagnosis. These pediatric cases underscore the limitations of relying solely on clinical presentation and neuroimaging and call to attention the essential role of neurosurgical intervention. The authors emphasize the need to maintain gliomatosis cerebri in the differential diagnosis of children presenting with diffuse neurological signs and MR imaging evidence of widespread, infiltrative lesions.

Pediatric gliomatosis cerebri mimicking acute disseminated encephalomyelitis.

Gliomatosis cerebri (GC) is a diffuse infiltrating glial neoplasm of astrocytic origin. GC in children is rare and difficult to diagnose, often presenting with a variety of signs and symptoms that may mimic encephalitis. We discuss here the presentation and diagnosis of GC in 2 children who were initially suspected to have acute disseminating encephalomyelitis. In this report we underscore the limitations of relying on clinical presentation and neuroimaging as well as the essential role of pathologic evaluation for the diagnosis of GC in children.

Eastern equine encephalitis virus infection and hemophagocytic lymphohistiocytosis in a 5-month-old infant.

Eastern equine encephalitis virus infection is a rare sporadic central nervous system infection transmitted by a mosquito vector. Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease associated with the inability of an overactive immune system to effectively respond to infections. Many viruses are known to trigger primary, as well as secondary, HLH. We report a pediatric case of eastern equine encephalitis virus-associated HLH which caused severe neurologic injury and death.

Clostridium perfringens enterotoxin as a novel-targeted therapeutic for brain metastasis.

Brain metastasis is the most commonly occurring intracranial tumor whose incidence seems to be increasing. With standard therapy, the average survival time of patients is approximately 8 months, and treatment often leads to neurologic dysfunction in long-term survivors, emphasizing the need for novel therapeutics. Clostridium perfringens enterotoxin (CPE) has recently been shown to rapidly and specifically destroy cancer cells expressing CPE receptors claudin-3 and claudin-4. Unfortunately, the utility of CPE is precluded by systemic toxicity because its receptors are expressed in numerous organs. Here, we provide the first preclinical evidence that CPE may be uniquely suited to the local treatment of brain metastasis. By immunohistochemical analysis, claudin-3 and claudin-4 were expressed frequently in metastases from breast (15 of 18), lung (15 of 20), and colon (12 of 14) carcinoma, and infrequently in metastases from renal cell carcinoma (2 of 16) and melanoma (2 of 16). In contrast, expression of claudin-3 and claudin-4 was absent in adjacent normal brain tissue. Further examination of the central nervous system (CNS) revealed low or undetectable levels of claudin-3 and claudin-4 in all regions tested by Western and immunohistochemical analysis. Treatment of breast cancer cell lines (MCF-7, MDA-MB-468, NT2.5-luc) and normal human astrocytes with CPE in vitro resulted in rapid and dose-dependent cytolysis exclusively in breast cancer cells, correlating with claudin-3 and claudin-4 expression. Moreover, intracranial CPE treatment significantly inhibited tumor growth and increased survival in two murine models of breast cancer brain metastasis, without any apparent local or systemic toxicity. These data suggest that CPE therapy may have efficacy against a wide variety of brain metastases without CNS toxicity.

Diethylstilbestrol (DES)-induced clear cell adenocarcinoma of the vagina metastasizing to the brain.

BACKGROUND: Primary vaginal clear cell adenocarcinoma (CCA) is a rare gynecological malignancy occurring predominantly in young females with a history of diethylstilbestrol exposure in utero. Vaginal CCA commonly metastasizes to the lungs and the supraclavicular lymph nodes; however we present a rare case of diethylstilbestrol-induced vaginal CCA with cerebral metastases. CASE DESCRIPTION: A 43-year-old woman with prenatal diethylstilbestrol exposure and history of vaginal CCA treatment 8 years prior to current presentation noted new onset headache and dizziness. MRI showed an enhancing mass in the right frontal lobe. Histopathology was consistent with CCA. CONCLUSIONS: This case report highlights the necessity of close extended follow-up in patients with a history of vaginal CCA and demonstrates the potential for spread of primary vaginal CCA to the brain.

Microvessel density in head and neck squamous cell carcinoma primary tumors and its correlation with clinical staging parameters.

OBJECTIVE: Our objective was to assess angiogenesis in head and neck squamous cell primary tumors and measure its correlation with tumor site and clinical and pathologic staging parameters. STUDY DESIGN: Patients from the tumor registries of the University of Louisville and affiliated hospitals who had biopsy-proven head and neck squamous cell carcinoma were retrospectively assessed over a 5-year period (1995-2000). METHODS: Patient records were reviewed for tumor site, TNM staging, surgical treatment, and tumor pathologic staging data. Cell blocks were obtained for each of the study patients, and CD31 staining was used to measure microvessel density (MVD) in areas of primary tumor hot spots. RESULTS: Twenty-eight consecutive patients met inclusion criteria and had adequate cell blocks for evaluation. MVD for T3 staged (41.2 MVD, mean) and T4 staged (36.4 MVD, mean) tumors were higher than earlier staged T1 staged (31.3 MVD, mean) and T2 staged (24.9 MVD, mean) tumors. Laryngeal T3 and T4 tumors had MVDs as high as 43.4 MVD (mean) and 40.4 MVD (mean), respectively, compared with a 23.9 MVD for T2 tumors. This difference was statistically significant (P < .01). Our report indicates a trend toward increasing MVD with N-stage. CONCLUSION: Our series demonstrates that there is a strong correlation between MVD in primary tumor hot spots and tumor T-stage, which implies that tumor angiogenesis may be a factor in tumor progression.