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.

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.

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.

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.

Assessment of PD-L1 expression in patients with neuroblastoma and renal tumors.

BACKGROUND: Programmed death 1 (PD-1) is a co-receptor which is located at the surface of cells like natural killer, monocytes, T and B cells. It has two ligands including programmed death ligand-1 (PD-L1) and ligand-2 (PD-L2). T cell functions are inhibited by activation of PD-1/PD-L1 pathway and this pathway is used by viruses and some tumor cells in order to escape from immune eradication. In our study we evaluated PD-L1 expression in the tissue specimens of patients with Wilms tumor, neuroblastoma and other renal tumors. METHODS: Totally 60 patients who were followed up at Gazi University Hospital with the diagnosis of neuroblastoma, Wilms tumor and other renal tumors were included. PD-L1 expression was examined in tumor samples of the patients. RESULTS: Positive staining with PD-L1 was detected only in two male patients. Both of them had neuroblastoma and advanced stage disease. None of the patients with Wilms tumor and other renal tumors had positive PD-L1 staining. CONCLUSIONS: Unlike adult tumors, PD-L1 expression is not common in childhood tumors due to differences in immune system between children and adults. Further studies are needed to establish the importance and effects of PD-1/PD-L1 pathway in pediatric tumors.

Risk factors for bacteremia in children with febrile neutropenia

Background/aim: Bacteremia remains an important cause of morbidity and mortality during febrile neutropenia (FN) episodes. We aimed to define the risk factors for bacteremia in febrile neutropenic children with hemato-oncological malignancies. Materials and methods: The records of 150 patients aged ≤18 years who developed FN in hematology and oncology clinics were retrospectively evaluated. Patients with bacteremia were compared to patients with negative blood cultures. Results: The mean age of the patients was 7.5 ± 4.8 years. Leukemia was more prevalent than solid tumors (61.3% vs. 38.7%). Bacteremia was present in 23.3% of the patients. Coagulase-negative staphylococci were the most frequently isolated microorganism. Leukopenia, severe neutropenia, positive peripheral blood and central line cultures during the previous 3 months, presence of a central line, previous FN episode(s), hypotension, tachycardia, and tachypnea were found to be risk factors for bacteremia. Positive central line cultures during the previous 3 months and presence of previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. Conclusion: Presence of a bacterial growth in central line cultures during the previous 3 months and presence of any previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. These factors can predict bacteremia in children with FN.

Comparison of FDG PET/MRI and FDG PET/CT in Pediatric Oncology in Terms of Anatomic Correlation of FDG-positive Lesions.

The aims of our study were to compare F-18 fluorodeoxyglucose (FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (CT) in pediatric oncology patients in terms of anatomic correlation of FDG-positive lesions, and also to compare diffusion-weighted imaging (DWI) with PET to assess the correlation between apparent diffusion coefficient (ADC) values and standardized uptake value (SUV). Sequential PET/CT and PET/MRI images and/or whole-body DWI and ADC mapping in 34 pediatric patients were retrospectively analyzed. FDG-positive lesions were visually scored for CT, T1-weighted, T2-weighted, and DWI images separately in terms of anatomic correlation of FDG-avid lesions. Correlation analysis was performed for SUV parameters and ADC values. Among 47 FDG-positive lesions identified concurrently on PET/CT and PET/MRI, 37 were positive on CT and 46 were positive on at least one MRI sequence (P=0.012). Among 32 FDG-positive lesions for which DWI were available, 31 could be clearly depicted on DWI, resulting in significant difference compared with CT alone in the detection of FDG-positive lesions. No correlation was found between ADC and SUV. FDG PET/MRI exhibits better performance than PET/CT in terms of anatomic correlation of FDG-avid lesions. Therefore, PET/MRI may be more advantageous than PET/CT, not only due to reduced ionizing radiation dose but also for a better depiction of FDG-avid lesions in pediatric PET imaging.

Epigenetic silencing of the tumor suppressor genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in childhood and adolescent lymphomas.

The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and adolescent lymphomas. A total of 96 patients with Hodgkin Lymphoma (HL, n = 41), Non-Hodgkin Lymphoma (NHL, n = 15), and reactive lymphoid hyperplasia (RLH, n = 40, as controls) are included in the research. The expression status of CDKN2A, SPI1, PRDX2, DLEC1, FOXO1, KLF4 and DAPK1 genes were measured with QPCR method after the RNA isolation from paraffin blocks of tumor tissue and cDNA conversion. DNA isolation was performed from samples with low gene expression followed by methylation PCR study specific to promoter regions of these genes. We found that SPI1, PRDX2, DLEC1, KLF4, and DAPK1 genes are significantly less expressed in patient than the control group (p = 0.0001). However, expression of CDKNA2 and FOXO1 genes in the patient and control groups were not statistically different. The methylation ratios of all genes excluding the CDKN2A and FOXO1 were significantly higher in the HL and NHL groups than the controls (p = 0.0001). We showed that SPI1, PRDX2, DLEC1, KLF4 and DAPK1 genes are epigenetically silenced via hypermethylation in the tumor tissues of children with HL and NHL. As CDKN2A gene was not expressed in both patient and control groups, we conclude that it is not specific to malignancy. As FOXO1 gene was similarly expressed in both groups, its relationship with malignancy could not be established. The epigenetically silenced genes may be candidates for biomarkers or therapeutic targets in childhood and adolescent lymphomas.

Patient With Niemann-Pick Type C Presenting With a Jaw Mass Characterized With Lymph Node Involvement by Niemann-Pick Cells.

Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. In NPC, accumulation of cholesterol in tissues could be seen not only in reticuloendothelial and nervous systems, but also in all systems. Our case is important for it being the first case of NPC with submandibular lymphadenopathy characterized with NPC cell infiltration.

Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population.

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.

Assessment of brachial artery reactivity, carotid intima-media thickness, and adhesion molecules in pediatric solid tumor patients treated with anthracyclines.

The aim of this study was to determine subclinical atherosclerosis and endothelial functional disturbance with measurement of carotid intima-media thickness (IMT), brachial artery reactivity (BAR), and levels of serum adhesion molecules in children with solid tumors who were treated with anthracyclines and are actually in complete remission. Fifty patients who were in remission and 30 healthy children were included in the study. Mean ages of patient and control groups were 13.5 ± 4.7 years (range: 3-23 years) and 12.00 ± 4.3 years (range: 4-21 years), respectively. The patients were divided into 3 groups according to cumulative doxorubicin dose: Group 1, ≤100 mg/m(2); Group 2, 101-299 mg/m(2); Group 3, ≥300 mg/m(2). The BAR and carotid IMT were measured in order to determine the endothelial function. The serum adhesion molecule levels in our patients and controls were also measured. The BAR of the patients with cumulative anthracycline dose ≥300 mg/m(2) was significantly lower than the patients with cumulative anthracycline dose ≤100 mg/m(2) and healthy controls (P =.005 and P =.003, respectively). Also, there was a negative correlation between brachial artery reactivity and increasing cumulative anthracycline dose (r = -.287, P =.044). We also found significant difference between the mean carotid IMT of the patients and the healthy children (P =.041). No statistically significant difference was detected between the serum levels of sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), sE-selectin of the patients and controls. The use of anthracyclines in pediatric patients with cancer could result in increase of the carotid IMT and endothelial dysfunction.

MRI and CT findings of isolated intracranial Rosai-Dorfman disease in a child.

Isolated intracranial Rosai-Dorfman disease (RDD) is extremely rare in pediatric patients. We present the case of a 22-month-old boy whom had isolated intracranial RDD involvement. To our knowledge, a parieto-occipital regional involvement without a dural tail sign has not been previously documented. Also, the mass contained hyperintense central T1 foci, and hypointense T2 and gradient echo foci; which are helpful in the differential diagnosis from meningioma. The magnetic resonance and computed tomography imaging findings are discussed and the follow-up course is presented in this paper.

Multisystem langerhans cell histiocytosis with thymic involvement diagnosed with anterior mediastinal mass in a 2-month-old boy.

Thymus gland involvement in Langerhans cell histiocytosis (LCH) is usually part of multi-system disease and may be more common than previously recognized. However, thymic involvement causing an anterior mediastinal mass is an extremely rare presentation of multisystem LCH. Here we report a 2-month-old-boy admitted to hospital with a giant anterior mediastinal mass with multisystem LCH involving the thymus, lungs, liver and skin. The differential diagnosis of mediastinal mass in children should also include LCH, especially multisystem disease. LCH should also be kept in mind in the differential diagnosis of skin lesions in infants, even if spontaneous regression occurs.

Imaging features of Burkitt lymphoma in pediatric patients.

Burkitt lymphoma is an aggressive and rapidly growing tumor that is curable and highly sensitive to chemotherapy. It can affect almost every tissue in the body, producing various clinical presentations and imaging appearances, according to the predilection of the different subtypes for certain sites. Awareness of its diagnostically specific imaging appearances plays an important role in rapid detection and treatment. In this pictorial review, we aimed to identify the most common imaging features of Burkitt lymphoma in pediatric patients.

Breastfeeding and Childhood Cancer: Is Breastfeeding Preventative to Childhood Cancer?

Breastfeeding is well-known to have a protective effect against infection in infants. It has been suggested that breast milk may play a role in the prevention of certain childhood cancer. We investigated this issue in a case-control study comprising 300 patients with childhood cancer. There was 73 patients (24.3%) with leukemia, 82 patients (27.3%) with lymphoma, and 146 patients (48.4%) with solid tumors (brain tumors, neuroblastoma, soft tissue sarcomas, germ cell tumors, renal tumor, bone tumor, retinoblastoma, hepatoblastoma, and others) and 316 controls matched for age and sex. Breastfeeding duration of the control group was found to be significantly longer than the patient group (X(2) = 57.774; P < .001). In conclusion, breastfeeding was found to be inversely associated with pediatric cancer in our study.

Thyroid abnormalities in survivors of childhood cancer.

OBJECTIVE: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors. METHODS: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups. RESULTS: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity. CONCLUSION: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

A complication to be aware of: hyperkalaemia following propranolol therapy for an infant with intestinal haemangiomatozis.

Infantile haemangiomas, benign vascular tumours seen in 4-10% of infants are characterised by their spontaneous remission following a 3-9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler ß-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment.