Fetal Wilm's tumor detection preceding the development of isolated lateralized overgrowth of the limb: a case report and review of literature.

Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein, we present the case of a full-term female infant diagnosed antenatally at 32 weeks of gestation with a right solid renal mass detected on routine prenatal ultrasound without polyhydramnios. At birth, the infant was healthy, with no evidence of dysmorphic features or abnormal laboratory tests to suggest a predisposition syndrome. Her family history was also unremarkable. A successful radical right nephrectomy was performed on day 2 of life revealing a classic WT. She received vincristine as adjuvant chemotherapy without any complications. At the age of 1 month, the infant developed isolated lateralized overgrowth of the right lower limb suspicious of Beckwith-Wiedemann syndrome. At the latest follow-up of 4 years, the child is healthy and disease-free with conserved asymmetry of lower limbs. The case provides insights into the challenging diagnosis and treatment of fetal WT. A review of the literature suggests that the presence of polyhydramnios is a worse prognostic factor while the combination of best supportive care and surgery remains the best management. Fetal WT can be associated with predisposition syndromes; however, their first manifestations can develop after the diagnosis of cancer has been made, as in our patient. We propose starting active surveillance programs and genetic testing for any case of fetal WT.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

The phenotypic spectrum of germline YARS2 variants: from isolated sideroblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2.

YARS2 variants have previously been described in patients with myopathy, lactic acidosis and sideroblastic anemia 2 (MLASA2). YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase, which is responsible for conjugating tyrosine to its cognate mt-tRNA for mitochondrial protein synthesis. Here we describe 14 individuals from 11 families presenting with sideroblastic anemia and YARS2 variants that we identified using a sideroblastic anemia gene panel or exome sequencing. The phenotype of these patients ranged from MLASA to isolated congenital sideroblastic anemia. As in previous cases, inter- and intra-familial phenotypic variability was observed, however, this report includes the first cases with isolated sideroblastic anemia and patients with biallelic YARS2 variants that have no clinically ascertainable phenotype. We identified ten novel YARS2 variants and three previously reported variants. In vitro amino-acylation assays of five novel missense variants showed that three had less effect on the catalytic activity of YARS2 than the most commonly reported variant, p.(Phe52Leu), associated with MLASA2, which may explain the milder phenotypes in patients with these variants. However, the other two missense variants had a more severe effect on YARS2 catalytic efficiency. Several patients carried the common YARS2 c.572 G>T, p.(Gly191Val) variant (minor allele frequency =0.1259) in trans with a rare deleterious YARS2 variant. We have previously shown that the p.(Gly191Val) variant reduces YARS2 catalytic activity. Consequently, we suggest that biallelic YARS2 variants, including severe loss-of-function alleles in trans of the common p.(Gly191Val) variant, should be considered as a cause of isolated congenital sideroblastic anemia, as well as the MLASA syndromic phenotype.

Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children's Oncology Group.

BACKGROUND: Children with malignant bone tumors have average 5-year survival rates of 60% to 70% with current multimodality therapy. Local control modalities aimed at preserving function greatly influence the quality of life of long-term survivors. In developing countries, the limited availability of multidisciplinary care and limited expertise in specialized surgery and pediatric radiation therapy, as well as financial cost, all form barriers to achieving optimal outcomes in this population. METHODS: We describe the establishment of a collaborative pediatric bone tumor program among a group of pediatric oncologists in Lebanon and Syria. This program provides access to specialized local control at a tertiary children's cancer center to pediatric patients with newly diagnosed bone tumors at participating sites. Central review of pathology, staging, and treatment planning is performed in a multidisciplinary tumor board setting. Patients receive chemotherapy at their respective centers on a unified treatment plan. Surgery and/or radiation therapy are performed centrally by specialized staff at the children's cancer center. Cost barriers were resolved through a program development initiative led by St Jude Children's Research Hospital. Once program feasibility was achieved, the Children's Cancer Center of Lebanon Foundation, via fundraising efforts, provided continuation of program-directed funding. RESULTS: Findings over a 3-year period showed the feasibility of this project, with timely local control and protocol adherence at eight collaborating centers. We report success in providing standard-of-care multidisciplinary therapy to this patient population with complex needs and financially challenging surgical procedures. CONCLUSION: This initiative can serve as a model, noting that facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close administrative coordination all greatly contributed to the success of the program.

Pandemic (H1N1) 2009 influenza in pediatric hematology/oncology units in Lebanon.

BACKGROUND: The impact of pandemic (H1N1) 2009 influenza on immunocompromised patients in western countries has been described, but reports from pediatric patients in the Middle East or Arab countries are deficient. In this study, we describe the clinical characteristics of children with hematological malignancies and laboratory-proven H1N1 influenza. PATIENTS AND METHODS: Patients were recruited from 3 pediatric hematology/oncology units in Lebanon. A confirmed case of pandemic (H1N1) 2009 influenza is a clinically suspected case with positive H1N1 test by either a rapid immunofluorescence test or by real-time polymerase chain reaction. Data were collected retrospectively from the medical charts. RESULTS: From October 2009 to March 2010, 14 immunocompromised children were infected with H1N1 influenza. Eight were male and 6 were female. The median age of patients was 4.5 years (range, 1 to 14). All children were hospitalized and treated with oseltamivir. Twelve children responded to treatment; the other 2 patients with severe respiratory distress were transferred to intensive care unit and resuscitated but died after 7 and 12 days. CONCLUSIONS: Immunocompromised children infected with pandemic 2009 influenza may respond very well when the diagnosis and treatment are rapid. However, on the basis of our experience, if the underlying disease is more severe (immunodeficiency with significant immunosuppressive treatment and induction of high-risk leukemia), the odds of mortality are likely greater.

Hemophagocytic lymphohistiocytosis with Munc13-4 mutation: a cause of recurrent fatal hydrops fetalis.

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder of immune regulation that leads to a hyperinflammatory syndrome responsible for fever, hepatosplenomegaly, cytopenia, and coagulopathy. Although presentation usually occurs in early infancy, antenatal presentation is extremely rare. To our knowledge, we are first to report genetically confirmed FHL in 2 consecutive siblings who presented with hydrops fetalis that led to spontaneous intrauterine death at 38 and 30 weeks of gestation. Because the diagnosis of FHL has important implications for genetic counseling, we suggest that FHL be considered in the differential diagnosis of nonimmune hydrops fetalis.

Inflammatory myofibroblastic tumor of the mesentery associated with high fever and positive Widal test.

Inflammatory myofibroblastic tumor (IMT) is associated in 15-30% of cases with systemic symptomatology, such as prolonged fever, weight loss, elevated erythrocyte sedimentation rate (ESR), anemia, thrombocytosis, and leukocytosis. We report the case of a 4-year-old Lebanese boy who presented with high-grade fever of long duration, and a single (unpaired) positive Widal agglutination test. Blood culture was negative. A diagnosis of typhoid fever was made. An abdominal (mesenteric) IMT was incidentally discovered, 30 days after the fever had appeared. After surgery, the fever disappeared immediately, and the ESR returned to normal. We strongly favor the possibility of a false positive Widal test, due to polyclonal increase in serum immunoglobulins, which often occurs in IMT. We also think that IMT might be a mimicker of typhoid fever, both clinically and serologically. Physicians, especially pediatricians practicing in endemic areas, should probably be aware of this mimicry.