Bone and Soft Tissue: Ewing sarcoma

Ewing sarcoma is a bone or soft tissue sarcoma most commonly diagnosed in adolescents and young adults. It is one of the pediatric small, round, blue cell tumors and a fusion gene-driven cancer

Characterization of Pulmonary Metastases in Children With Hepatoblastoma Treated on Children\u27s Oncology Group Protocol AHEP0731 (The Treatment of Children With All Stages of Hepatoblastoma): A Report From the Children\u27s Oncology Group.

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children\u27s Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those \u3c 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis

Teratoid Hepatoblastoma—Our Experience

Hepatoblastomas (HB) are the most common pediatric liver tumor with several subgroups described, of which teratoid HB is the rarest. The aim of this study is to characterize the histologic and phenotypic spectrum of teratoid HB in order to better understand the biology and behavior of these tumors. A retrospective analysis of all teratoid HB diagnosed at a major pediatric hospital as well as the consultation files of one of the authors (SR) was performed with the available clinical data and surgical pathology material reviewed. A detailed immunohistochemical workup was also performed. A total of 28 cases were included from patients ranging from 5 to 84 months of age and a M:F ratio of 1.07:1. Four patients had syndromic associations. In 14/28 cases, the tumors contained primitive glandular elements with histologic and immunophenotypic overlap with the yolk sac tumor which in two cases became predominant in metastatic sites. One case had extensive primitive neural epithelium mimicking a primitive neuroectodermal tumor (PNET). Other unique elements included melanin, mature neuroglial tissue, rhabdomyoblastic differentiation, and neuroendocrine carcinoma-like areas (n = 2). In conclusion, this study provides the largest series of teratoid HB to date with clinical and outcome data, highlights previously undescribed or under-recognized histologic patterns in these tumors, and describes the immunohistochemical profile of these tumors to aid in diagnosis

Viral ventilator-associated pneumonia: Uncovering tip of the iceberg

Context: Hospital-acquired infections are frequently encountered by the physicians for ailments demanding prolonged hospitalization, especially in intensive care units, where patients are often mechanically ventilated. The organisms most often implicated are bacteria; viral etiology is infrequent. Aims: The study aims at reviewing lung pathology at autopsy in mechanically ventilated children admitted in pediatric intensive care unit (PICU) to assess the incidence of viral ventilator-associated pneumonias (VAP). Setting and Design: Retrospective analysis. Materials and Methods: Among the 275 children who had been autopsied, 13 who had been admitted in the PICU satisfied the criteria for VAP. These cases were analyzed on the basis of clinical data and pulmonary pathology. Depending on the overall histology, the cases were classified as being viral or bacterial in etiology. Immunohistochemistry (IHC) for detection of viral antigens was also performed. Results: Of the 13 children, nine (five males and four females) had shown the histomorphologic features, suggesting viral inflammation. The mean age was 33 months. Falling oxygen saturation and increasing respiratory distress had necessitated ventilator support. Acute lymphocytic bronchiolitis, interstitial pneumonitis, diffuse alveolar damage, and necrotizing pneumonia were the histological features. The viruses identified in five patients were adenovirus, respiratory syncytial virus and cytomegalovirus. Conclusion: This communication, though not representing the true incidence, emphasizes that a proportion of nosocomial infections is due to viral infections. This should alert the treating intensivists to actively pursue investigations to confirm viral etiology

Unusual adrenal cortical tumor of unknown biologic potential: A nodule in a nodule in a nodule

Adrenocortical tumors are uncommon neoplasms in childhood. Most pediatric adrenal tumors are virilizing and carcinomas are more common than adenomas. Recent molecular data suggest an adenoma-to-carcinoma progression sequence in adrenal cortical neoplasms. We report a case of a 5-year-old boy who presented with virilizing symptoms secondary to an adrenal tumor that was resected laparoscopically. The bulk of the tumor was a large, yellow mass with typical features of an adrenal cortical adenoma. In the center was a well-circumscribed tan-brown nodule that was distinct from the adenoma and had oncocytic features. A third minute focus (3.0 mm) was noted that was not circumscribed or encapsulated, but showed marked pleomorphism and abundant mitoses, including atypical forms and increased Ki67 compared with the outer 2 nodules. Molecular analysis to assess the clonality and mutation rates of the 3 distinct areas showed only 2 genetic loci with allelic imbalances. © 2005 Society for Pediatric Pathology

Transforming Growth Factor-β1 Selectively Recruits microRNAs to the RNA-Induced Silencing Complex and Degrades CFTR mRNA under Permissive Conditions in Human Bronchial Epithelial Cells

<p>Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (<italic>CFTR</italic>) gene lead to cystic fibrosis (CF). The most common mutation F508del inhibits folding and processing of CFTR protein. FDA-approved correctors rescue the biosynthetic processing of F508del-CFTR protein, while potentiators improve the rescued CFTR channel function. Transforming growth factor (TGF-β1), overexpressed in many CF patients, blocks corrector/potentiator rescue by inhibiting CFTR mRNA in vitro. Increased TGF-β1 signaling and acquired CFTR dysfunction are present in other lung diseases. To study the mechanism of TGF-β1 repression of CFTR, we used molecular, biochemical, and functional approaches in primary human bronchial epithelial cells from over 50 donors. TGF-β1 destabilized CFTR mRNA in cells from lungs with chronic disease, including CF, and impaired F508del-CFTR rescue by new-generation correctors. TGF-β1 increased the active pool of selected micro(mi)RNAs validated as CFTR inhibitors, recruiting them to the RNA-induced silencing complex (RISC). Expression of F508del-CFTR globally modulated TGF-β1-induced changes in the miRNA landscape, creating a permissive environment required for degradation of F508del-CFTR mRNA. In conclusion, TGF-β1 may impede the full benefit of corrector/potentiator therapy in CF patients. Studying miRNA recruitment to RISC under disease-specific conditions may help to better characterize the miRNAs utilized by TGF-β1 to destabilize CFTR mRNA