Pediatric Plasmablastic Lymphoma in the Setting of CD70 Deficiency.

Combined immunodeficiency due to CD70 deficiency is characterized by increased susceptibility to infections, hypogammaglobulinemia, and malignancy. These patients typically present with chronic Epstein Barr virus (EBV) viremia, severe EBV-related hemophagocytic lymphohistiocytosis, lymphoproliferation, and Hodgkin and non-Hodgkin lymphomas. Plasmablastic lymphoma (PBL) is an extremely rare malignancy in all ages and is predominantly seen in male adults with human immunodeficiency virus infection. EBV infection, immunosuppression, solid organ transplantation, and age-related immune deterioration are also suspected causes of PBL. Nevertheless, there is scarce data about its association with primary immunodeficiencies in the literature. Here, we present the first case of a CD70-deficient pediatric patient with PBL.

Prognostic Values of Primary Tumor Textural Heterogeneity and Blood Biomarkers in High-risk Neuroblastoma.

PURPOSE: The aim of this study was to evaluate the prognostic value of textural parameters of primary tumors, serum lactate dehydrogenase (LDH), D -dimer, and ferritin in high-risk neuroblastoma patients. PATIENTS AND METHODS: The imaging findings of 22 neuroblastoma patients (14 girls and 8 boys; age, 36.6 ± 34.2 [range: 5 to 138] months) who underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography for primary staging before therapy between 2009 and 2020 were retrospectively evaluated. Positron emission tomography-derived metabolic data (maximum standard uptake value, mean standard uptake value, metabolic tumor volume, and total lesion glycolysis) and textural features of primary tumors were obtained. Serum LDH, D -dimer, and ferritin levels at the time of diagnosis were recorded. Univariate and multivariate Cox proportional hazards regression models were used to identify predictors for progression-free survival (PFS) and overall survival (OS). Survival curves were estimated by using the Kaplan-Meier method. RESULTS: The median follow-up duration after diagnosis was 63 months (range: 5 to 141 mo). The median PFS and OS in all patients were 19 and 72 months, respectively. In multivariate Cox regression analyses with backward stepwise selection, grey level size zone matrix_size zone emphasis (GLSZM_SZE) was found as an independent predictor for both PFS and OS. Serum ferritin level was also found as an independent predictor for PFS. The Kaplan-Meier survival analysis showed that higher serum LDH, D -dimer, GLSZM_SZE, and zone size nonuniformity were significantly associated with shorter OS. CONCLUSION: Serum LDH, D -dimer, ferritin levels, and GLSZM_SZE of primary tumors may be used as prognostic biomarkers to identify patients with worse prognoses in high-risk neuroblastoma. GLSZM textural features showing higher tumor heterogeneity are significantly associated with shorter PFS and OS.

Low vitamin B12 level in relation to trace element, total sialic acid and antioxidant enzymes in children with vitamin B12 deficiency anemia.

In this study, children with vitamin B12 deficiency anemia (V-B12DA) and control subjects were evaluated for erythrocyte glutathione peroxidase, catalase and superoxide dismutase enzyme activities, glutathione, malondialdehyde, serum total sialic acid, total antioxidant status, cobalt, chromium, copper, selenium, vanadium, zinc, iron, lead, magnesium, calcium, sodium, potassium, chloride, phosphorus levels, and the associations of these variables were assessed. The study included 50 children with V-B12DA and 50 control subjects. It was found that the V-B12DA group was significantly lower than the control group, with regard to the mean±the standard error of the mean levels of cobalt (0.089±0.009; 0.058±0.0063 µmol/L, p<0.01), selenium (2.19±0.087; 1.88±0.057 µmol/L, p<0.01), vanadium (1.31±0.053; 1.18±0.035 µmol/L, p<0.05), magnesium (3.02±0.15; 2.73±0.068 µmol/L, p<0.05), zinc (50.76±1.96; 42.23± 1.53 µmol/L, p<0.001), and vitamin B12 (427.20±21.45; 157.08±3.96 pg/mL, p<0.001). Moreover, a significant elevation in total sialic acid (1.44±0.050; 1.61±0.043 mmol/L, p<0.01), and mean corpuscular volume (MCV) (75.37±0.95; 79.91±1.14 fL, p<0.01). It was observed that in the V-B12DA, significantly linear correlations were observed between cobalt - vitamin B12 (r=0.334; p=0.025), vanadium - MCV (r=0.315; p=0.017), vitamin B12 - MCV (r=-0.297; p=0.026). The findings of the study indicated that the levels of cobalt, vanadium significantly associated with traditional vitamin B12-deficiency parameters. Vitamin B12 and MCV should be measured together with cobalt, vanadium for monitoring the vitamin B12 deficiency anemia.

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center.

OBJECTIVE: This study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom. METHODS: This study included 61 children aged between 2 and 18years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom. RESULTS: Of the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p<0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia. SIGNIFICANCE: Resective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.

Safety and efficacy of COVID-19 vaccines in children and adolescents with cancer.

BACKGROUND: Children with cancer have a higher morbidity and mortality due to COVID-19. Vaccination of children with cancer is important. In this study, we aimed to investigate the effectiveness and side effects of the COVID-19 vaccines in children and adolescents with cancer. METHODS: Fifty-eight patients from four centers were included in the study. Antibodies to the SARS-CoV-2 spike protein levels were measured. Vaccine-related complaints were recorded. RESULTS: There were 33 male and 25 female patients. The mean age was 16.9±2.3 years. In 58.6% of cases, the diagnosis was hematological malignancies. Twenty patients were currently under treatment, while 38 had completed the treatment. Forty-eight patients received chemotherapy ± radiotherapy, 13 received immunotherapy, and 3 underwent stem cell transplantation. CoronoVac© and BNT162b2© vaccines were administered in 24% and 76%, respectively. The mean antibody level was lower in patients who received CoronaVac© than that of BNT162b2©, although the difference was not significant. The levels were within the protective limits in both groups. No significant difference was found in antibody levels according to diagnostic subgroups, treatment status, type of treatment, line of treatment, disease status and time between vaccines and measurement of antibody level. The most common side effects were pain at the injection site (37.9%) and malaise/weakness (17.2%), which were similar for both vaccines. CONCLUSIONS: Our study showed that both mRNA and inactivated vaccines elicit an immune response in children with cancer. However, the seroconversion rate is significantly higher in mRNA vaccines. Side effects were similar to those seen in healthy children.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

The etiologies and management of spinal cord compression in childhood cancers: Are we aware of the emergency of cord compression?

BACKGROUND: The spinal cord compression causes irreversible long-term permanent neurological sequelae. This study aims to increase awareness of childhood cancers that cause cord compression by comparing histopathological diagnosis, treatments, and survival rates to the literature. METHODS: Seventy-three patients (38 male, 35 female) with spinal cord compression, among 1085 patients diagnosed with solid tumors at Gazi University Department of Pediatric Oncology between 1991 and 2021 were retrospectively evaluated. RESULTS: The mean time between the onset of complaints and diagnosis was 27.5± 24.9 (2-150) days. The first three most common tumors that caused cord compression; were central nervous system tumors in 22 (30%), neuroblastoma in 17 (23%), and malignant germ cell tumors in 8 (10%) cases. Of the patients, 46 (63%) had compression due to extradural masses, and 27 (37%) patients had an intradural compression. The most common symptoms were pain in 60 (82%), weakness in 57 (78%), and pins and needles in 28 (38%) patients, respectively. The clinical physical neurological examination findings were motor deficit in 62 (84%), and deep tendon reflex changes in 54 patients (73.9%). Compression findings were detected in 58 (79.5%) patients at diagnosis, and in 15 (20.5%) of them during follow-up. The most common level of compression was seen in the thoracolumbar region in 19 (26%) cases. In 65 (89%) patients with cord compression, corticosteroids were given as anti-edema treatment. Surgical excision was performed in 39 (53%) patients. Spinal radiotherapy was given to 35 patients (48%) with radiosensitive tumors. Chemotherapy protocols were started in 52 (71.2%) cases according to their diagnoses. Complete neurological recovery was achieved in 33 (45%) patients. The 5-year overall survival rates for solid tumors with extradural compression and intradural compression were 62% and 22%, respectively (p=0.002). CONCLUSIONS: Neurological sequela-free recovery is possible with early diagnosis and urgent treatment. Spinal compression must be detected by detailed systemic and neurological examination and imaging methods. Patients should be rapidly transferred to pediatric oncology units after starting anti-edema treatment.

Retrospective Analysis of Paediatric Glial Tumours that Required Modern Molecular Techniques.

AIM: To determine if previous histological grading systems were sufficient or unreliable with a limited repository of modern techniques. MATERIAL AND METHODS: The pathology reports of pediatric neurosurgery patients between 2019-2022 were accessed. Data on patients that needed unattainable further molecular investigation were extracted. Data were noted from electronic archives, including their sex, age, histologic grade, location, resection type, survival, and therapy. RESULTS: Out of 61 surgeries, 17 patients needed further investigation for a proper 2022 World Health Organization (WHO) diagnosis. Seven were deceased, and nine were alive. Two of 10 patients with low-grade gliomas and five of six patients with highgrade gliomas were deceased. Data on one foreign patient with high-grade glioma was inaccessible. The average survival was 9 months for the deceased. CONCLUSION: Modern molecular techniques such as next-generation sequencing and methylation profiling are the state-ofthe- art methods, but it is hard for developing and underdeveloped countries to utilize such methods. The classification schemes, diagnostic key figures, and treatment modalities are developed using these techniques, but the less developed world is incapable of achieving these. We are trying to hybridize the modern and classic modalities, and the results of our study show that for overall survival, there is still not much difference. More economic and feasible techniques should be produced and summarized for the rest of the world.

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants.

AIM: To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma (RB) at Gazi University Faculty of Medicine's Department of Pediatric Oncology. METHODS: All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department, October 2016 to May 2021 were evaluated retrospectively. The RB1 gene was analyzed by next-generation sequencing (NGS) technique in DNAs obtained from peripheral blood samples of the patients. RESULTS: This study included 53 cases with 67 RB-affected eyes during the study period. The mean age was 24.6 (median: 18.5, range: 3-151)mo. There were 15 (22.3%) Group D eyes and 39 (58.2%) Group E eyes. The RB1 gene was sequenced by the NGS method in 19 patients. Heterozygous RB1:NM_000321.3: c.54_76del (p.Glu19AlafsTer4) variant was detected in a 15-month-old female with bilateral RB. Heterozygous RB1:NM_000321.3: c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB. The intronic RB1:NM_000321.3: c.1332+4A>G variant was detected in patient 14, a 13-month-old male with unilateral RB. The RB1:NM_000321.3: c.575_576del (p.Lys192SerfsTer10) variant was found in an 18-month-old female with an allele frequency of 37%. These variants have not been reported in the literature and mutation databases. CONCLUSION: Four novel variants are described and one of them is found in two different patients. This data is crucial for assessing prognosis. It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Cyclopentolate eye drops-induced anaphylaxis in an infant.

BACKGROUND: Cyclopentolate is frequently used as a mydriatic agent during ophthalmological examinations in childhood and hypersensitivity reactions associated with this drug are rare. We aim to report an infant who experienced anaphylaxis due to cyclopentolate eye drops. CASE: A nine-month-old girl, who was being followed up with a diagnosis of retinoblastoma, presented for consultation for urticaria, cough, stridor, and dyspnea that developed after the administration of topical cyclopentolate to the eyes. The patient was diagnosed with anaphylaxis and treated with adrenaline. During the follow-up, tropicamide was used safely as an alternative drug. CONCLUSIONS: In children, hypersensitivity reactions due to cyclopentolate are very rare. Only four pediatric patients were reported in the literature to have developed an allergic reaction after the administration of cyclopentolate eye drops. We present here the youngest patient who developed anaphylaxis with cyclopentolate eye drops. Anaphylaxis due to cyclopentolate should be kept in mind, rapidly recognized, and treated when a reaction develops.

Prognostic value of fluorodeoxyglucose positron emission tomography derived metabolic parameters and textural features in pediatric sarcoma.

PURPOSE: The aim of this study was to evaluate the prognostic value of PET-derived metabolic features and textural parameters of primary tumors in pediatric sarcoma patients. METHODS: The imaging findings of 43 patients (14 girls and 29 boys; age 11.4 ± 4.4 years) who underwent 18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography for primary staging prior to therapy between 2005 and 2020 were retrospectively evaluated. The diagnoses were osteosarcoma in 10, rhabdomyosarcoma in 10, and Ewing sarcoma in 23 patients. PET metabolic data and textural features of primary tumors were obtained. Cox proportional hazards regression models were used to identify predictors for progression-free survival and overall survival. Survival curves were estimated by using the Kaplan-Meier method. RESULTS: Distant metastases were detected in primary staging in 13 patients (30.2%). The median follow-up duration after diagnosis was 28 months (range: 10-171 months). In multivariate Cox regression analysis, the presence of distant metastasis and neighborhood grey-level difference matrix_Contrast (ngldm_Contrast) were found as independent predictors for both progression-free survival and overall survival. Grey-level zone length matrix_Zone-length nonuniformity (glzlm_ZLNU) was also found as an independent predictor for overall survival. The Kaplan-Meier survival analysis showed that higher ngldm_Contrast and glzlm_ZLNU values of primary tumors were significantly associated with shorter progression-free survival and overall survival. CONCLUSION: In addition to the presence of distant metastasis at initial diagnosis, textural features of primary tumors may be used as prognostic biomarkers to identify patients with worse prognosis in pediatric sarcoma. Higher tumor heterogeneity is significantly associated with shorter progression-free survival and OS.

The first report of West Nile virus infection in a child from Turkey.

Seroprevalence data indicate that West Nile virus (WNV) activity is present in Turkey; however, no pediatric cases of WNV infection have been reported to date. WNV is an emerging flavivirus in Turkey, and in September2010, the Turkish Ministry of Health reported the first seven cases of laboratory-confirmed WNV infection from five different cities in the western part of the country. This is the first report of a child from central Anatolia, indicating the existence of the virus in other regions of the country.

A case of pediatric psoriasis achieving remission after allogenic bone marrow transplantation.

BACKGROUND: Psoriasis is an inflammatory skin disease in which the cells and molecules of innate and adaptive immunity are involved in the pathogenesis. Aplastic anemia is a bone marrow deficiency syndrome that is characterized by an extreme reduction in the number of blood cells as a result of failure in hematopoiesis. Allogenic hematopoietic stem cell transplantation is a promising treatment for Aplastic Anemia and it is important to note that other comorbid diseases like psoriasis- since both have some common pathogenetic mechanisims- might achieve remission after treatment. CASE: We present a 12-years-old male patient who underwent bone marrow transplantation for aplastic anemia and his psoriasis vulgaris lesions completely regressed. The final follow-up visit on day 150 also revealed no sign of the pre-transplantation skin and scalp lesions. CONCLUSIONS: This is the first case of pediatric psoriasis together with aplastic anemia that achieved complete remission of psoriasis after bone marrow transplantation. Our case report needs to be supported by prospective studies involving larger patient populations.

Increased anti- EBV VCA IgG antibody levels are associated with need for surgery in patients developing upper respiratory tract complications.

INTRODUCTION: The immune reaction developing against Ebstein-Barr virus (EBV) infection may be one of the major determinants of severe adenoid hypertrophy (AH) and chronic otitis media with effusion (COME) needing surgery. In this study, we aimed to investigate the relationship between these antibodies and the need for surgery due to complications such as severe AH and COME. METHODS: Sixty consecutive patients <15 years old who were admitted to our outpatient clinics between January 2014 and December 2015 with severe AH ±â€¯COME and underwent adenoidectomy ±â€¯ventilation tube insertion and 129 control patients who had a history of EBV infection at least three months before the inclusion to the study without current symptoms of upper airway obstruction and middle ear disease were included in this study. Two groups of patients and a control group were studied: a) children who underwent adenoidectomy alone with no middle ear disease (group 1), b) children with COME and AH who underwent adenoidectomy and tympanostomy with ventilation tube insertion (group 2), and c) control group without adenoid hypertrophy or otitis media with effusion. RESULTS: Patients who needed surgery (Group 1 and 2) had significantly higher levels of anti-EBV VCA IgG antibodies than control patients (19.8 ±â€¯16.4 vs. 1.7 ±â€¯0.8 S/CO, p < 0.001). Anti-EBV VCA IgM levels did not differ between groups. Group 2 patients had also higher levels of Anti-EBV VCA IgG antibodies than group 1 patients (35.8 ±â€¯16.7 vs. 11.8 ±â€¯8.5 S/CO, p < 0.001). ROC curve analysis resulted in a cut-off point of 2.92 S/CO level for anti-EBV VCA IgG antibodies for need for surgery in EBV infected patients with 97% sensitivity and 98% specificity. CONCLUSION: Markedly increased serum anti-EBV VCA IgG antibodies in children who developed upper respiratory tract complications such as severe AH and COME may show the significant role of enhanced immune system reaction in the pathogenesis of these complications due to EBV infection.