Wiskott-Aldrich Syndrome: Description of a New Gene Mutation With Normal Platelet Volume.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by an increased incidence of autoimmunity, malignancy, microthrombocytes with thrombocytopenia, eczema, and recurrent infections. In this case report, we present a novel mutation, hemizygous for c.1125_1129delTGGAC mutation in the WAS gene, and a unique clinical presentation. Our patient was initially diagnosed with a milk protein allergy after presenting with a lower gastrointestinal bleed, leukopenia, and thrombocytopenia with normal platelet volume. However, signs of vasculitis and detection of microthrombocytes required additional testing and consideration of WAS. This case report illustrates the importance of retaining a high index of clinical suspicion despite normal platelet volume, as well as adding to the growing number of known mutations associated with WAS.

Langerhans cell sarcoma: case report and review of world literature.

Langerhans cell sarcoma is a rare malignancy with only 1 pediatric case (less than 15 y of age) reported. Here, we report the second case of Langerhans cell sarcoma in a child who presented with cord compression. This patient was treated with extensive surgical resection, postoperative chemotherapy, and involved-field radiation therapy. She completed therapy and remains in remission for 27 months. A review and analysis of all 53 cases published in the world literature is provided to help guide physicians treating this disease. Recently discovered genetic mutation involving BRAF is also discussed.

Meningiomas in children and adolescents: a meta-analysis of individual patient data.

BACKGROUND: The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS: Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS: From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). INTERPRETATION: Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. FUNDING: None.

Home pediatric compassionate extubation: bridging intensive and palliative care.

Compassionate home extubation for pediatric patients is a topic that seldom appears in the literature and is of unknown clinical importance. However, standards in pediatric intensive care unit (PICU) and among pediatric critical care physicians regarding end-of-life decisions are changing, including where and when patient extubation occurs. The authors' hospice recently consulted on an infant with spinal muscular atrophy in the PICU requiring mechanical ventilation, for whom further life-sustaining care was deemed futile. In consultation with the family, nursing staff, physicians, and the ethics committee, and following protocol guidelines, arrangements were made for this infant and his parents to be transported home. Once comfortable with his family, a small amount of lorazepam was given and the endotracheal tube removed. The infant died quietly about 20 minutes later. This case prompted the authors to review the current state of published articles covering this topic, suggest a protocol for implementing home extubation, realize imposed barriers, and discuss potential solutions. A well-developed plan for home extubation procedures may improve interactions with PICU and hospice services and at the same time provide additional choices for parents and patients wishing to maximize end-of-life quality outside the hospital setting.

Phase II investigation of docetaxel in pediatric patients with recurrent solid tumors: a report from the Children's Oncology Group.

BACKGROUND: Docetaxel, which is an antitubulin agent, has demonstrable activity against murine and human tumors. The current study was designed to determine response rates to docetaxel in various strata of recurrent solid tumors of childhood and to assess toxicity in a group of patients who were assigned to receive it. METHODS: Docetaxel was given at a dose of 125 mg/m2 once every 21 days as a 1-hour intravenous infusion for a maximum of 12 courses. From January 1997 to November 2001, 109 male patients and 68 female patients (total, 177 patients) were enrolled, and 173 patients were eligible. The median patient age at entry was 13 years (range, 1-27 yrs). One hundred sixty patients were evaluable for response. RESULTS: There were no deaths attributable to study drug. Hematologic toxicity was common during therapy. Dermatologic, neurologic, pulmonary, and infectious side effects as well as edema were significant. One patient each had acute myeloid leukemia, acute lymphoid leukemia, and high-grade glioma reported as secondary malignancies. One patient with osteosarcoma and 1 patient with rhabdomyosarcoma achieved a complete response. Partial responses were observed in patients with Ewing sarcoma (3 patients), osteosarcoma (1 patient), squamous cell carcinoma (1 patient), and medulloblastoma (1 patient). Seventeen patients had stable disease. The 1-year and 5-year overall survival rates for the 160 evaluable patients were 24% (standard error = 4%) and 6% (standard error = 2%), respectively. CONCLUSIONS: Docetaxel demonstrated activity in patients with recurrent Ewing sarcoma but was found to be ineffective for treating the other types of recurrent solid tumors that were studied.

Rhabdomyoblastic pulmonary lesions in a patient with Wilms tumor: choristomas or metastases?

New lesions that occur while patients are receiving treatment for malignant tumors may represent not only difficulties in arriving at the correct diagnosis, but also impact on subsequent therapeutic options. We encountered a patient developing new pulmonary lesions during and after receiving treatment for Stage II Wilms tumor (WT). The presence of mature rhabdomyoblasts in multiple biopsy specimens allowed rational decisions to be made regarding subsequent therapy. This and other published experiences suggest that patients with WT may develop choristomas or have tumors, which undergo cytodifferentiation. Methodologies are now available allowing differentiation of these two processes.

Meningiomas in children and adolescents.

PURPOSE: To review the diagnosis, treatment, and long-term outcome of children and adolescents with meningiomas diagnosed by a single institution and compare these findings with other published data. PATIENTS AND METHODS: A 25-year retrospective analysis of 18 patients with meningioma diagnosed at Children's Hospital Medical Center, Cincinnati, Ohio was performed. A literature review of published reports was undertaken to compare evaluation. treatment, and outcome for similar patients. RESULTS: Patients ranged from ages 19 months to 17 years at diagnosis. The most common symptoms were headache (5) and seizures (5), although most patients had multiple symptoms. The brain was the primary location of tumor in 17 patients, with the remaining tumor located in the spine. Comorbid diagnoses were common, including developmental delay, balanced chromosomal translocation, type I diabetes mellitus, neurofibromatosis, Klinefelter syndrome, and seizures. Eleven patients had gross total resection performed. Four patients had malignant meningiomas. Two patients were treated with radiotherapy only, one had chemotherapy only, and two underwent both. Karyotype abnormalities most commonly involved chromosome 22, but other abnormalities were present. Sixteen patients remain alive and two patients, having had malignant tumors, are dead of disease. Long-term sequelae include seizures, diabetes insipidus, blindness, neuropsychologic abnormalities, and multiple surgical procedures. Only three patients are self-described as being without problems. CONCLUSIONS: Based on this study and a literature review, the roles of surgery, radiation, and chemotherapy remain unclear. Long-term outcome for patients with meningiomas, especially as it relates to cognitive function, is rarely reported. This group of patients has a high incidence of morbidity associated not only with treatment but also with preexisting diseases. These data indicate the need for a national cooperative group study to better understand the evaluation, treatment, and outcome for children and adolescents who are treated for meningiomas.