Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal condition. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) overlaps with HLH. Human-herpesvirus 6 (HHV6) is a common childhood infection that rarely causes neurological complications. HHV6-related HLH/DRESS has only been described in case reports . Procedure: From all admissions to Children’s Minnesota with positive HHV6 the records of a subgroup and additional patients from Israel formed a cohort of patients with HHV6-rlated HLH using HLH-2004 criteria. Results: Of 50 consecutive HHV-6 patients, five (10%) developed HLH/DRESS and with two from other centers a cohort of seven is described (six with HLH and one with DRESS). Four had concurrent viruses as possible pathogenic factors. All had thrombocytopenia, elevated soluble IL2 receptor (CD25), and fever; 6/7 had elevated ferritin, and all 5 evaluated had bone marrow hemophagocytosis. Most (6/7) had CNS involvement, all had liver abnormalities, and most had coagulopathy. One patient with Kabuki syndrome was on gammaglobulin replacement therapy, whereas none of the other patients had immune deficiency. One patient had a heterozygous pathogenic variant of TNFSF13B, with no immunodeficiency. Four required etoposide and dexamethasone therapy, while three were also treated with ganciclovir/valganciclovir. The outcome was excellent (median follow-up almost 6 years) with no neurologic sequelae, recurrent HLH, or need for hematopoietic stem cell transplantation. Conclusions: The high incidence of HHV6-related HLH in admitted patients indicates a strong need for vigilance regarding this condition. HHV6-related HLH has a high rate of CNS manifestations, but the outcome in this group of patients was excellent.

Background: COVID-19, the novel coronavirus has caused a global pandemic affecting millions of people around the world. Although children, including children with cancer, have been found to be affected less commonly and less severely than adults, indirect effects of the pandemic on the diagnosis and treatment of children with cancer have been less described. Methods: A survey was performed in the four largest tertiary pediatric hematology-oncology medical centers in Israel. Clinical and laboratory data were collected from the medical files of patients diagnosed or treated with cancer during April-October 2020. Results: Seventeen patients are described, who had significant delay in diagnosis or treatment of cancer. These represent approximately 10% of all the pediatric cancer diagnosed during the study period in these centers. A main cause of delay was fear of exposure to COVID-19 (fears felt by the patient, parent, physician, or decision-makers at the institution; or the implementation of national guidelines). Delays also resulted from co-infection with COVID-19 and the attribution of the oncologic symptoms to the infection. In addition, treatment was delayed of patients already diagnosed with cancer, due to COVID-19 infection detected in the patient, a family member, or a bone marrow donor. Conclusion: Fear from the COVID-19 pandemic may result in delayed diagnosis and treatment of children with cancer, which may carry a risk to dismal prognosis. It is crucial that pediatricians and patients alike remember that other diseases still prevail and must be thought of and treated in a timely fashion.

Background: Accurate and swift tissue diagnosis is extremely important for the timely initiation of treatment in pediatric oncology. In our department, ultrasound guided core needle biopsy (US guided CNB) is used for tissue diagnosis. In 2016, we added on-site cytology, allowing for an immediate primary diagnosis. We retrospectively reviewed our performance in terms of safety and accuracy for CNBs and on-site cytology Procedure: All pediatric biopsies performed in our hospital between February 2016, and December 2019 were included. Patient clinical, procedural and follow up data were collected. CNB pathology and cytology results were compared to final pathologic diagnosis. Results: We included 185 patients for which 210 biopsies were performed; Median latency time to biopsy was one day. Altogether, we had 164 tumors, (148 malignant,16 benign) and 46 other lesions. 159 tumors were correctly diagnosed by CNB; five malignant tumors were misdiagnosed as benign. The sensitivity of our US guided CNB is 96.7%, specificity 100%, and accuracy 97.6%. On-site cytology was performed in 41 cases; 36 malignant tumors, 2 benign tumors and 3 reactive lymph nodes. The cytologist correctly differentiated tumor from inflammation in all cases, and diagnosed the precise tumor type in 38 cases, with accuracy of 93% for final diagnosis. We had no complications related to the procedure or sedation. Conclusions: US guided CNB with on-site TI cytology for suspected malignancy in the pediatric population highly available, safe and accurate, with real time diagnosis in most cases. The accelerated diagnostic root has huge impact on patient care.