The liver is the third most common site of abdominal tumors in children. This review article aims to summarize current evidence surrounding identification and diagnosis of primary hepatic tumors in the pediatric population based upon clinical presentation, epidemiology, and risk factors as well as classical imaging, histopathological, and molecular diagnostic findings. Readers will be able to recognize the features and distinguish between benign and malignant hepatic tumors within different age groups.

Objective Previous small-scale studies suggest that maternal smoking lowers neonatal body iron. Our objective was to study and compare the relationship between maternal and infants’ body iron in smokers and non-smokers in a large matched-pair cohort. Method This was a prospective cohort study involving 144 mothers – 72 smokers and 72 non-smokers and their respective infants. Samples were obtained from maternal blood and infants’ cord blood at delivery for serum transferrin receptor (sTfR) and ferritin levels. Serum TfR and ferritin levels were measured by RAMCO ELISA and RIA assays. The total body iron (TBI) was calculated using the sTfR/ferritin ratio. Results Maternal total body iron and smoking status Women who smoked had lower sTfR, higher ferritin and higher body iron compared to nonsmoking women. Infant’s total body iron, measurements at birth and smoking status In contrast to their respective mothers, we found a small but statistically significant negative correlation between smoking and infants’ total body iron. The number of PPD smoked was negatively correlated with infants’ ferritin and total body iron. The number of days smoked during pregnancy was also negatively correlated with infants’ ferritin and total body iron and positively correlated with infants' sTfR. Birth weight was lower in babies of smokers compared to nonsmokers (mean /- SD =3270 +/-475 vs. 3393 g +/- 475 g, p=0.03). Correlation studies revealed that birth weight in infants of smokers was negatively correlated with PPD smoked and number of days smoked. Birth length in the same infants was also negatively correlated with PPD smoked and number of days smoked. Conclusion Mothers who smoked during pregnancy had higher iron stores but their newborn infants had lower iron stores than those of non-smoking mothers. There may be a negative dose-dependent response between fetal smoke exposure and infant iron stores. Disclosures: No relevant conflicts of interest to declare.

Rationale:Hepatoblastoma is a rare malignancy. Approximately 100 cases are diagnosed yearly in the United States. The highest incidence occurs in infants and in children younger than 5 years. Cases involving patients older than 5 years are very rare. We describe the case of a patient who was diagnosed with hepatoblastoma at an atypical age of presentation for this type of malignancy. We also performed Ovid MEDLINE search for hepatoblastoma and epidemiology reports occurring in children between the ages of 5 and 18 years. In this article we review the epidemiology and summarize case reports published between 1997 and 2012 of patients with hepatoblastoma, who were older than 5 years.Patient concerns and diagnosis:Our patient is an 11 year old boy with stage IV hepatoblastoma with lung and omental metastases at diagnosis.Interventions:The patient received 7 cycles of chemotherapy following the treatment plan of COG protocol AHEP 0731, off study. He also had tumor resection and omentectomy and achieved complete remission.Outcomes:He later had disease recurrence and after undergoing treatment with different modalities, ultimately died of his disease. Review of SEER program data shows that the incidence of hepatoblastoma in children above the age of 5 years is too infrequent to be calculated. Literature review revealed 13 cases of patients diagnosed at age older than 5 years. Most cases were published due to unusual associations and/or complications. There are no obvious unifying characteristics for these cases, although there may be a slight male preponderance and many patients in this selected series presented with elevated Alpha-fetoprotein.Lessons:The reported case is rare, given the very low incidence of hepatoblastoma outside of infancy. A systematic review of characteristics and outcomes for patients older than 5 years who are enrolled in cooperative group hepatoblastoma trials may reveal important information about the epidemiology and tumor biology in this rare patient population.

HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment syndrome, graft rejection/failure, acute graft-vs-host disease, infections systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy). Moreover, this period is usually marked by febrile illness, cytopenia, and a "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin and sCD25. These parameters overlap with the diagnostic criteria for HLH. Such confounding factors make the management of post-HSCT HLH quite challenging. We illustrate this critical issue with case report of a patient who was diagnosed with HLH after allogeneic HSCT for tAML. He received MP and CsA for HLH but VP-16 was not administered due to fear of severe myelosuppression. Fortunately, he responded well to treatment and remains in remission to date. We recommend caution while using HLH-94/HLH-2004 guidelines for the diagnosis and management of post-HSCT HLH. In this article, we pinpoint these issues with a brief review of all the pediatric cases and clinical studies of post-HSCT HLH along with a critical evaluation of its various diagnostic criteria. Finally, based on the limitations of current diagnostic criteria, we suggest a need for formulating disease-specific diagnostic criteria for post-HSCT HLH.

Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.

Gene rearrangements involving the histone lysine methyltransferase 2A gene (KMT2A) are identified in 4-7% of childhood acute lymphoblastic leukaemias (ALL). 1 The rearrangement is associated with a poor prognosis, presentation in infancy and lymphoblasts lacking CD10 with expression of myeloid markers. 2-4 KMT2A fusions are promiscuous with 135 different transfusion partner genes (TPGs) reported. 1 The vast majority fuse the 5 0 end of KMT2A in-frame to a TPG at the 3 0 end. 1 However, reciprocal translocations (TPG-KMT2A) are also found either in association with KMT2A-TPG fusions or rarely, in some instances, by themselves without a corresponding KMT2A-TPG fusion. 1 Here, we describe an isolated ATP5L-KMT2A reciprocal fusion in a 15-month-old male with B lymphoblastic leukaemia/lymphoma (B-ALL). The University Hospitals Cleveland Medical Center/Case Western Reserve University's Institutional Review Board granted approval for the study under number #02-14-36. The patient presented at 14 months in Kuwait with refusal to walk, malaise and fevers. A complete blood count demonstrated: white blood cells 22Á4 9 10 9 /l, haemoglobin 75 g/l, platelets 24 9 10 9 /l. A bone marrow work-up revealed 91Á5% blasts. Phenotypically, the cells were CD10 À , CD19 + , CD20 À , CD34 + , CD45 dim , TdT + (partial) and MPOconsistent with BALL. Genetic studies showed a normal karyotype and fluorescent in situ hybridization (FISH) was negative for t(12;21) (p13;q22), t(9;22)(q34;q11), t(1;19)(q23;p13Á3) and KMT2A (11q23) rearrangements. The patient was classified as standard risk BALL and received three-drug induction therapy per UK-MRC-ALL 2011. On day 15 of induction, persistent blasts (66%) were present and treatment was intensified to include anthracyclines and an additional dose of PEG asparaginase. He was transferred to our institution after completing induction therapy. Persistent disease was noted upon arrival at our institution with 48% marrow blasts with a phenotype as previously reported (Fig 1A, B). Repeat FISH for KMT2A rearrangement was negative with two yellow signals suggesting two intact copes of the KMT2A gene (Fig 1C). To further evaluate for a molecular aberration, cells were assessed for novel gene fusions using a NeoGenomics (Fort Myers, FL, USA) ALL fusion profile which identified an ATP5L-KMT2A fusion (Fig 2), discussed below. He received consolidation therapy for very high-risk BALL patients per COG AALL1131 followed by two cycles of blinatumomab. Subsequently he underwent a matched, unrelated umbilical cord transplant and presently is seven months post-transplant and disease-free. ized to exons 9-11 of the KMT2A gene 1. Only 6Á5% of KMT2A fusions occur with breakpoints outside of this Correspondence

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.

Background: Vitamin B 12 (B 12) is an essential nutrient for DNA synthesis and cell metabolism. While B 12 deficiency has been extensively studied, the importance of elevated B 12 is under investigation. High levels are described in adults with malignancies and many other conditions. Limited and conflicting data exists pertaining to children with elevated levels. Methods: A single institution retrospective study was conducted. Patients younger than 18 years with high B 12 levels during the period of 2010-2018 were included. Patients with a history of or concurrent B 12 therapy were excluded. B 12 levels, complete blood cell counts, concurrent, prior and future diagnoses were collected. Results: A total of 384 patients with high B 12 levels were identified. An indication for obtaining a B 12 level was documented for 296 patients (77.1%) with most common reasons being fatigue (n = 36, 12.2%), failure to thrive (n = 32, 10.8%) and anemia (n = 25, 8.4%). Seven indications, (2.4%) were obtained as follow-up of a previous malignancy. Within the 5 year follow up 47.8% of patients (n=142) had documentation of future diagnoses. The top 3 subspecialties with future diagnoses were psychiatry (n=53, 23.0%), gastroenterology (n=32, 13.9%) and neurology (n=26, 11.3%). Only one patient developed an oncologic diagnosis, Langerhans Cell Histiocytosis. Conclusion: Our study found no association of elevated B 12 with pediatric malignancies. However, we highlight a possible link between elevated B 12 and neuropsychiatric and gastroenterological processes. More studies are needed to further delineate the importance of elevated B 12 in the pediatric population.