Unusual paediatric spinal myxopapillary ependymomas: Unique molecular entities or pathological variations on a theme?

Ependymomas are the commonest type of spinal glioma which represent a group of relatively benign tumours. Myxopapillary ependymoma (MPE) is a common variant found within the distal spinal cord around the conus. These two entities are clearly differentiated on the basis of their characteristic histological and molecular features. Rare variants of MPE's are described in the literature to have the propensity to metastasise and grow in extraspinal locations despite appearing histologically identical to their more benign relatives. Here, we describe two unusual cases of MPE and utilise DNA methylation analyses to compare their molecular signatures with known molecular subtypes of ependymoma in an attempt to distinguish whether these tumours represent a unique subset of disease.

A novel technique of serial biopsy in mouse brain tumour models.

Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804) is a tyrosine kinase inhibitor (TKI), which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4) are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used. Immunodeficient mice received cortical implants of the human glioblastoma cell line, U87MG, modified to express the constitutively-active EGFR mutant, EGFRvIII, GFP and luciferase. Tumour growth was monitored using bioluminescence imaging. Upon attainment of a moderate tumour size, free-hand biopsy was performed on a subgroup of animals. Animal monitoring using a neurological severity score (NSS) showed that all mice survived the procedure with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. The technique was used to evaluate dacomitinib-mediated inhibition of EGFRvIII two hours after drug administration. We show that serial tissue samples can be obtained, that the samples retain histological features of the tumour, and are of sufficient quality to determine response to treatment. This approach represents a significant advance in murine brain surgery that may be applicable to other brain tumour models. Importantly, the methodology has the potential to accelerate the preclinical in vivo drug screening process.

Successful induction and maintenance of long-term remission in a child with chronic relapsing autoimmune hemolytic anemia using rituximab.

Childhood autoimmune hemolytic anemia (AIHA) of the warm type is usually successfully managed with corticosteroids and/or immunoglobulin infusions. In a small proportion of patients AIHA follows a more severe and protracted pathway resulting in the use of immunosuppressive therapy and frequently culminating with the need for splenectomy. Rituximab is an anti-CD20 (B-cell) monoclonal antibody used for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma. Case reports on the use of rituximab for childhood AIHA are scant. The authors describe the first report in which rituximab was effectively employed to induce a long-term remission in a young child with the longest history of chronic relapsing AIHA prior to receiving rituximab. All immunosuppressive therapy was successfully discontinued and splenectomy was avoided.

A rare case of adenoviral fulminant hepatic necrosis after chemotherapy.

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.