Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

There are only 8 published cases of symplastic hemangioma (SH), a relatively recently described, distinct benign entity characterized by pleomorphic vascular smooth muscle and interstitial cells in a pre-existing, long-standing vascular lesion. Seven of these cases were of SH in cutaneous locations, and 1 case was described in the mediastinum. We report the case of the 12-year-old girl with a nasopharyngeal tumor mass with prominent symplastic changes arising in the background of a combined capillary arteriovenous malformation. After critical analysis of all published cases of SH, it is clear that these lesions commonly represent capillary arteriovenous malformations (CAVM) with ancient/symplastic changes according to current terminology proposed in the classification required by the International Society for the Study of Vascular Anomalies (ISSVA). This is the first such lesion reported in a mucosal location and presenting in the pediatric age group. CAVM with ancient/symplastic change follows a benign clinical course, but it can simulate a malignant vascular tumor.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. BALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of BALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with BALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis.

Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.

Introduction Extraskeletal Ewing sarcoma (ES) is a highly malignant neoplasm occurring most commonly in the thoracic wall and the paravertebral region. ES belongs to the group of small round cell tumors and displays pathognomonic structural abnormalities of the EWS gene. The aim of this article was to present extraskeletal ES in an extremely rare anatomic location, an unusual clinical presentation, and modified treatment strategy. Case outline A 15-year-old boy was admitted to the hospital with acute abdominal pain in the right iliac region. During urgent operation, because of suspected appendicitis with periappendicular infiltrate, partly hemorrhagic tumor tissue was discovered in the preperitoneal space. Histopathological and immunohistochemical analyses revealed a tumor resembling extraskeletal ES. A postoperative CT scan showed the tumor rest, which was completely removed in the second operation. Molecular genetic analysis confirmed extraskeletal ES by finding the EWSR1-FLI1 fusion gene. Chemotherapy and radiotherapy according to the VAC protocol were started, and the patient is free of the disease eight months after the first operation. Conclusion Our case is the fourth case of extraskeletal ES located in the abdominal wall, the second case confirmed by the molecular genetic finding, and the first case described in children at this anatomic site. Due to an extremely rare location, unusual clinical presentation, and needed genetic analysis, the tumor treatment strategy was modified with good short-term results.