Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.

Background: Lung ultrasound (LUS) is a widely available technique allowing rapid bedside detection of different respiratory disorders. Its reliability in the diagnosis of community-acquired lung infection has been confirmed. However, its usefulness in identifying infections caused by specific and less common pathogens (e.g., in immunocompromised patients) is still uncertain. Methods: This systematic review aimed to explore the most common LUS patterns in infections caused by intracellular, fungal pathogens or mycobacteria. Results: We included 17 studies, reporting a total of 274 patients with M. pneumoniae, 30 with fungal infection and 213 with pulmonary tuberculosis (TB). Most of the studies on M. pneumoniae in children found a specific LUS pattern, mainly consolidated areas associated with diffuse B lines. The typical LUS pattern in TB consisted of consolidation and small subpleural nodes. Only one study on fungal disease reported LUS specific patterns (e.g., indicating “halo sign” or “reverse halo sign”). Conclusions: Considering the preliminary data, LUS appears to be a promising point-of-care tool, showing patterns of atypical pneumonia and TB which seem different from patterns characterizing common bacterial infection. The role of LUS in the diagnosis of fungal disease is still at an early stage of exploration. Large trials to investigate sonography in these lung infections are granted.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare pediatric soft tissue neoplasm composed of small round tumor cells with prominent stromal desmoplasia, polyphenotypic differentiation and EWSR1-WT1 gene fusion. We, herein, present a unique case of DSRCT, exhibiting a pure spindle cell morphology, absence of desmoplastic stroma and showing a novel EWS-WT1 fusion transcript. Methods: A 12-year-old boy presented multiple intra-abdominal, confluent and mass-forming nodules that affected the entire abdominal and pelvic cavities. Results: Histologically, the nodules were composed of spindle cells with scant cytoplasm and oval nuclei arranged into short, intersecting fascicles and set in a scant, non-desmoplastic, stroma. Immunohistochemically, neoplastic cells were stained with vimentin, desmin, WT-1 (C-terminus antibodies) and EMA. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed the presence of an unusual chimeric transcript, composed of an in-frame junction of exon 9 of EWS to exon 7 of WT1, confirming the histological diagnosis of DSRCT. Conclusions: The present case contributes to widen the morphological spectrum of this entity; notably, the additional presence of a novel chimeric fusion transcript contributes to making the present case even more unique. Whether the detection of the above-mentioned fusion transcripts could explain the unusual morphology of the tumor remains to be established.

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.

IgG4-related disease (IgG4-RD) is a recently discovered immune-mediated fibroinflammatory condition, uncommon in the pediatric population, that could involve multiple organs and induce cancer-like lesions and organ damage. Its main features are multiple injuries in different sites, a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and often high serological concentrations of IgG4. Autoimmune pancreatitis is the most common manifestation, mainly in adults. Two cases of IgG4-RD in children with lymph node localization of disease are reported. Localized or systemic lymph node involvement is common, but lymph node enlargement as the first and only manifestation of IgG4-RD is unusual, and therefore, hard to differentiate from other diseases. IgG4-related lymphadenopathy (IgG4-LAD) is most likely a distinct disease, described as isolated lymphadenopathy, related to the presence of elevated numbers of IgG4-positive plasma cells. Both disorders are likely to be misdiagnosed in children because they are characterized by rare and polymorphic features. IgG4-RD and IgG4-LAD should be considered in the differential diagnosis of disorders characterized by lymphadenopathy of uncertain etiology.

Background: Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest–derived disorders.Aim of the study: To explore the occurrence of NBTs within NF1 and to report on its natural history, therapeutic strategies, and outcomes in an Italian cohort of children with NF1 and in the literature.Subjects and Methods: Study (a): a retrospective analysis of questionnaire-based data [years 1979–2017] derived from the databases of the Italian Registry for Neuroblastoma (RINB) of the Italian Society of Pediatric Onco-Haematology (AIEOP); and Study (b): a systematic review search on NF1/NB co-occurrence.Results: Study (a) identified eight children with NBTs, 0.2% of patients registered in the RINB, fulfilling the diagnostic criteria for NF1. The primary site of NBTs was abdominal in six patients. The NBTs were neuroblastoma (NB) in five patients, ganglioneuroblastoma (GNB) in one, patient, and ganglioneuroma (GN) in two. Metastatic diffusion occurred in three out of eight children. MYCN gene testing, performed in the tumors of five patients, resulted not-amplified. The major features of NF1 included the following: NF1 family history in four patients, café-au-lait spots in all, freckling in six, Lisch nodules in three, and neurofibromas in three. With regard to the outcome, four children survived three of these for the progression of NB and one for a second tumor. Study (b) identified 12 patients with NF1/NB from the years 1966–2017, and the median age at diagnosis was 27 months (range = 0–168 months). The primary site of NB was thoracic. The prevalent histotype was NB in nine patients, GNB in two, and GN in one. Eight/nine NBs were metastatic. The MYCN gene was amplified in the only studied case. The NF1 features included NF1 family history in seven patients; the major NF1 features were café-au-lait spots in nine patients, freckling in one, Lisch nodules in none, and neurofibromas in six. The outcome was good for only two children, while eight children died of neuroblastoma, at a median age of 49.5 months (range = 2.4–174 months), with a median survival time of 21.75 months after diagnosis.Conclusions: To our knowledge, this represents the first systematic study on the occurrence of NBTs in NF1. This confirms that NBs are rare per se in the setting of NF1 (0.2% of all NBs) and even if compared to the overall frequency of malignancies in NF1 (i.e., 14.7%). The male:female ratio in study (a) (0.6) was different from what was recorded in study (b) (1.5) and in line with the overall increased frequency of malignancies in females with NF1. The median ages at diagnosis of NB in either study (a) or (b) were concordant with what occurred in the NB population. In study (a) versus study (b), the frequency of metastatic diffusion was lower, likely indicating less awareness on work-ups for malignancies in old NF1 series in the literature. The outcome was much better in study (a) than in study (b), indicating that multidisciplinary treatment for NB is highly recommended.