Pulmonary veno-occlusive disease after respiratory syncytial virus infection in a post hematopoietic stem cell transplantation patient.

Background: Pulmonary veno-occlusive disease (PVOD) is a rare but fatal complication of hematopoietic stem cell transplantation (HSCT). Although literature on PVOD post-HSCT is scarce, a recent study has indicated that this condition may be underestimated. Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes common cold in healthy individuals but may lead to severe lower respiratory infection accompanied by respiratory distress in infants and immunocompromised individuals, such as post-HSCT patients. However, little is known about the relationship between PVOD and RSV infections. Case report: A 4-year-old boy was diagnosed with metastatic neuroblastoma and underwent intensive chemotherapy, autologous HSCT, and allogeneic cord blood transplantation (CBT). He experienced PVOD on day 194 following CBT after displaying upper respiratory symptoms and positive RSV antigen test results approximately one month prior. Pathological examination of a lung biopsy specimen revealed lung injury suspected to be associated with viral infection in addition to PVOD-related findings, suggesting that RSV infection might have contributed to the onset of PVOD. Conclusions: The patient's clinical history and histological findings indicated that RSV could have triggered the development of PVOD under potential endothelial damage caused by HSCT and other prior treatments. Common respiratory viral infections, such as RSV infection, may evoke the development of PVOD.

A case of recurrent refractory cervical primary histiocytic sarcoma treated with pembrolizumab.

Histiocytic sarcoma (HS) is a rare disease with a poor prognosis. The efficacy of immune checkpoint inhibitors for this disease has not been established. A 13-year-old boy with HS refractory to conventional chemotherapy was treated with pembrolizumab, an immune checkpoint inhibitor. After treatment, the primary lesion and the bone metastases showed improvement; however, new metastatic lesions also occurred. This case suggests that the effect of immune checkpoint inhibitors might depend not only on programmed death ligand-1 expression and the ratio of tumor mutational burden, but also on other factors, such as the tumor microenvironment. Evaluation of more cases is required to identify biomarkers that define the efficacy of immune checkpoint inhibitors.

Investigation of patient factors associated with the number of transfusions required during chemotherapy for high-risk neuroblastoma.

BACKGROUND: Blood transfusion is an important supportive care for high-risk neuroblastoma. When the number of transfusions increases, transfusion-associated adverse reactions may be more problematic. However, the factors determining the degree of myelosuppression and the number of transfusions during chemotherapy for high-risk neuroblastoma remain unclear. MATERIALS AND METHODS: We investigated patient factors determining the number of required transfusions in 15 high-risk neuroblastoma patients who received five courses of chemotherapy. Clinical data, cytokine profile and colony-forming assay with bone marrow samples at diagnosis were analysed. RESULTS: The required number of transfusions of both platelets and erythrocytes decreased once in the second course and then increased as the course progressed. The variability among cases increased as the chemotherapy course progressed. In cases of low peripheral blood platelet count and lower fibrinogen level at diagnosis, the number of platelet transfusions was higher during chemotherapy. In contrast, there was a negative correlation between the forming ability of granulocyte-macrophage or erythroid colonies and the number of erythrocyte transfusions in the latter period. CONCLUSION: In the early stages of chemotherapy, bone marrow infiltration in neuroblastoma and/or coagulopathy complication may cause thrombocytopenia and requirement of platelet transfusion; conversely, in the later stages, the number of erythrocyte transfusions may be defined by the patient's inherent hematopoietic ability. These factors may be useful in predicting the required number of transfusions.

Aggressive growing of the infantile cavernous hemangioma of the calvaria: a case report and review of literature.

INTRODUCTION: Primary intraosseous cavernous hemangiomas of the skull are very rare in the pediatric age group and usually slow-growing tumors. CASE REPORT: We present a case of 5-month-old girl with a left occipital cavernous hemangioma that is rapidly growing. The subcutaneous occipital tiny mass was first noted at birth, and the lesion became rapidly enlarged in size and became soft for 3 months. The left occipital subcutaneous lesion was 4.0 × 4.0 × 2.0 cm (AP × LR × HT) in size. There was no history of trauma or bone tumor in her family. She underwent resection of the lesion, and a pathologic diagnosis of calvarial cavernous hemangioma was made. No recurrence was seen 1 year after surgery. CONCLUSION: The rapid growth of the infant cavernous hemangioma might be related to not only bleeding and/or congestion of the lesion but the immature thin skull of the infant.

Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and ß-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.

Transient Deformation of Neutrophils in Kawasaki Disease.

In the treatment of Kawasaki disease, resistance to high-dose immunoglobulin intravenous (IGIV) can occur. The neutrophil morphology analyses in 17 patients revealed that transient pseudo-Pelger-Huët anomaly was more frequently detected in the IGIV-resistant group. This finding may aid the prediction of IGIV resistance.

Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.

Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma.

Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR-1/2/3 and PDGFR-α/ß expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post-resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib.

Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors.

Alagille syndrome is a multisystem developmental disorder characterized by bile duct paucity, congenital heart disease, vertebral anomalies, posterior embryotoxon, and characteristic facial features. Alagille syndrome is typically the result of germline mutations in JAG1 or NOTCH2 and is one of several human diseases caused by Notch signaling abnormalities. A wide phenotypic spectrum has been well documented in Alagille syndrome. Therefore, monozygotic twins with Alagille syndrome provide a unique opportunity to evaluate potential phenotypic modifiers such as environmental factors or stochastic effects of gene expression. In this report, we describe an Alagille syndrome monozygotic twin pair with discordant placental and clinical findings. We propose that environmental factors such as prenatal hypoxia may have played a role in determining the phenotypic severity.

Extraosseous Ewing sarcoma in the mesentery: the first report of cases in children.

Extraosseous ewing sarcoma (EES) is a rare soft-tissue tumor usually found in the extremities or paraspinal region. We describe the case of a 4-year-old boy with a large cystic mass in the mesentery diagnosed as mesenteric lymphangioma preoperatively and as EES after partial resection and histopathological examination. EES in the mesentery is extremely rare, with only 2 reports described in the English literature. This represents the first report of EES in a child.

Interleukin-8-producing primary cardiac undifferentiated sarcoma in a child with sustained fever.

We report the case of a 12-year-old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin-8 (IL-8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL-8 continued to increase with tumor progression accompanied by elevated neutrophil count and C-reactive protein. IL-8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.

Pretransplant-corrected QT dispersion as a predictor of pericardial effusion after pediatric hematopoietic stem cell transplantation.

Pericardial effusion is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). Therefore, the identification of risk factors could improve the outcome. Prolonged QT dispersion (QTD) and corrected QTD (QTcD) are associated with serious arrhythmias and sudden death in many forms of heart disease. However, no study has evaluated the efficacy of QTD and QTcD to predict pericardial effusion post-HSCT. We studied 89 pediatric HSCT patients to identify preoperative risk factors for pericardial effusion with particular focus on QTD and QTcD. Pericardial effusion occurred in 15 patients (cumulative onset rate: 17.4%) within one year post-HSCT, of which 8 (9.2%) were symptomatic. Patients with pericardial effusion following allogeneic HSCT showed significantly lower overall survival; however, pericardial effusion was not the direct cause of death in any patient. Univariate and multivariate analyses revealed that transplantation-associated thrombotic microangiopathy (TA-TMA) was an independent risk factor for post-HSCT pericardial effusion. In addition, pretransplant QTcD was significantly prolonged in the pericardial effusion group. These results suggest that pediatric patients with abnormally prolonged QTcD before the preparative regimen for HSCT should be regularly followed-up by echocardiography to detect pericardial effusion, particularly when accompanied by complications including TA-TMA.