Neuroblastic Tumors Research Articles

Sinh thiết kim dưới hướng dẫn của siêu âm chẩn đoán u sau phúc mạc ở trẻ em: hồi cứu trên 52 bệnh nhân

Bachground: Ultrasound-guided large core needle biopsy technique has widely been applied in the diagnosis of adult abdominopelvic, mediastinal cavity, breast and neck tumors. There are few reports on ultrasound-guided biopsy using large-core needle in pediatric solid tumor. This study was to evaluate the ultrasound features and the diagnostic value of ultrasound-guided core needle biopsy for pediatric retroperitoneal tumors. Methods: The pediatric patients with retroperitoneal tumor that determined by ultrasound, CT or MRI examination and underwent ultrasound guided core needle biopsy from October 2018 to January 2020 were reviewed at Vietnam National Children’s Hospital. A minimum of five cores in each case was obtained. 13 patients were operated and had surgical pathology results. The ultrasound features and the diagnostic accuracy of ultrasound-guided core needle biopsy were evaluated. Results: Fifty - two patients (25 males, 27 females) were enrolled into the study. Conventional ultrasound examination showed irregular hypoechoic or mixed echo masses and calcification and liquefied necrosis. The ratio of vascular encased tumors was 61.5%. The quality of tissue sample was enough to make diagnosis was 98.1% (51/52). Only one case was misdiagnosed because of inadequate tissue sample. The diagnostic accuracy of ultrasound guided core needle biopsy compared to subsequent surgical histopathology was 76.9 % (10/13). Retroperitoneal tumor pathology varied with neuroblastic tumor was 86.3% (60.8% NB, 11.8% GNB and 13.7% GN), ACC was 5.9%, germ cell tumor was 4.0% (2.0% teratoma, 2.0% yolk sac tumor) and extra renal malignant rhadoid tumor was 2.0%. No serious complication, hemorrhage or infection occurred. Conclusions: Ultrasound-guided core needle biopsy seems to be an accurate, minimally invasive, and safe diagnostic method of pediatric retroperitoneal tumor.

A Confidence Habitats Methodology in MR Quantitative Diffusion for the Classification of Neuroblastic Tumors.

Simple SummaryThere is growing interest in applying quantitative diffusion techniques to magnetic resonance imaging for cancer diagnosis and treatment. These measurements are used as a surrogate marker of tumor cellularity and aggressiveness, although there may be factors that introduce some bias to these approaches. Thus, we explored a novel methodology based on confidence habitats and voxel uncertainty to improve the power of the apparent diffusion coefficient to discriminate between benign and malignant neuroblastic tumor profiles in children. We were able to show this offered an improved sensitivity and negative predictive value relative to standard voxel-based methodologies.Background/Aim: In recent years, the apparent diffusion coefficient (ADC) has been used in many oncology applications as a surrogate marker of tumor cellularity and aggressiveness, although several factors may introduce bias when calculating this coefficient. The goal of this study was to develop a novel methodology (Fit-Cluster-Fit) based on confidence habitats that could be applied to quantitative diffusion-weighted magnetic resonance images (DWIs) to enhance the power of ADC values to discriminate between benign and malignant neuroblastic tumor profiles in children. Methods: Histogram analysis and clustering-based algorithms were applied to DWIs from 33 patients to perform tumor voxel discrimination into two classes. Voxel uncertainties were quantified and incorporated to obtain a more reproducible and meaningful estimate of ADC values within a tumor habitat. Computational experiments were performed by smearing the ADC values in order to obtain confidence maps that help identify and remove noise from low-quality voxels within high-signal clustered regions. The proposed Fit-Cluster-Fit methodology was compared with two other methods: conventional voxel-based and a cluster-based strategy. Results: The cluster-based and Fit-Cluster-Fit models successfully differentiated benign and malignant neuroblastic tumor profiles when using values from the lower ADC habitat. In particular, the best sensitivity (91%) and specificity (89%) of all the combinations and methods explored was achieved by removing uncertainties at a 70% confidence threshold, improving standard voxel-based sensitivity and negative predictive values by 4% and 10%, respectively. Conclusions: The Fit-Cluster-Fit method improves the performance of imaging biomarkers in classifying pediatric solid tumor cancers and it can probably be adapted to dynamic signal evaluation for any tumor.

Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors

BackgroundTo assess the feasibility and possible value of semi-automated diffusion weighted imaging (DWI) volumetry of whole neuroblastic tumors with apparent diffusion coefficient (ADC) map evaluation after neoadjuvant chemotherapy.MethodsPediatric patients who underwent surgical resection of neuroblastic tumors at our institution from 2013 to 2019 and who received a preoperative MRI scan with DWI after chemotherapy were included. Tumor volume was assessed with a semi-automated approach in DWI using a dedicated software prototype. Quantitative ADC values were calculated automatically of the total tumor volume after manual exclusion of necrosis. Manual segmentation in T1 weighted and T2 weighted sequences was used as reference standard for tumor volume comparison. The Student’s t test was used for parametric data while the Wilcoxon rank sum test and the Kruskal-Wallis test were applied for non-parametric data.ResultsTwenty seven patients with 28 lesions (neuroblastoma (NB): n = 19, ganglioneuroblastoma (GNB): n = 7, ganglioneuroma (GN): n = 2) could be evaluated. Mean patient age was 4.5 ± 3.2 years. Median volume of standard volumetry (T1w or T2w) was 50.2 ml (interquartile range (IQR): 91.9 ml) vs. 45.1 ml (IQR: 98.4 ml) of DWI (p = 0.145). Mean ADC values (× 10− 6 mm2/s) of the total tumor volume (without necrosis) were 1187 ± 301 in NB vs. 1552 ± 114 in GNB/GN (p = 0.037). The 5th percentile of ADC values of NB (614 ± 275) and GNB/GN (1053 ± 362) provided the most significant difference (p = 0.007) with an area under the curve of 0.848 (p < 0.001).ConclusionsQuantitative semi-automated DWI volumetry is feasible in neuroblastic tumors with integrated analysis of tissue characteristics by providing automatically calculated ADC values of the whole tumor as well as an ADC heatmap. The 5th percentile of the ADC values of the whole tumor volume proved to be the most significant parameter for differentiation of the histopathological subtypes in our patient cohort and further investigation seems to be worthwhile.

Prp19 Is an Independent Prognostic Marker and Promotes Neuroblastoma Metastasis by Regulating the Hippo-YAP Signaling Pathway

Pre-mRNA processing factor 19 (Prp19) was previously reported to be involved in tumor progression. However, Prp19 expression and its functions remain elusive in neuroblastoma. Here, we aim to identify the functions and mechanisms of Prp19 in neuroblastoma. Neuroblastic tumor tissue microarrays and two independent validation data sets indicate that Prp19 is associated with high-risk markers and bone marrow metastasis and serves as a prognostic marker for worse clinical outcomes with neuroblastoma. Gain- and loss-of-expression assays reveal that Prp19 promotes invasion, migration, and epithelial–mesenchymal transition (EMT) of neuroblastoma cells in vitro. Bioinformatics analysis of RNA-seq data shows that the expressions of YAP and its downstream genes are significantly inhibited after downregulation of Prp19. Prp19 and YAP expression in metastatic lymph nodes is higher than in situ neuroblastoma tissue. Further experiments show that Prp19 regulates YAP expression and consequently affects cell invasion, migration, and EMT in neuroblastoma by pre-mRNA splicing of YAP. In conclusion, our findings provide the first evidence that Prp19 is a potential therapeutic target and prognostic biomarker for patients with neuroblastoma.

Pathology of Peripheral Neuroblastic Tumors

Pathology of Peripheral Neuroblastic Tumors

Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease.

It can be challenging to recognize undifferentiated/immature ganglion cells, especially single forms. Ganglion cells and glia are derived from enteric neural crest cells (ENCCs), a group of autonomic nervous system (ANS)-lineage neural crest progenitors that PHOX2B regulates. Phox2b is an excellent marker for neoplastic and non-neoplastic ANS cells (eg, peripheral neuroblastic tumors [pNTs]). We hypothesized that Phox2b immunohistochemical staining (IHC) would also be useful for detecting ENCCs. Hematoxylin and eosin, calretinin IHC, and Phox2b IHC were reviewed on 21 pull-through specimens and on a cohort of 12 rectal biopsies. Phox2b IHC demonstrated nuclear positivity in all of the ganglion cells across the different phases of differentiation without background staining. The Phox2b result correlated with the morphological findings, calretinin IHC results, and diagnoses based on the routine diagnostic method. The intensity was uniformly strong in the undifferentiated/immature forms and became variable in the mature forms; this pattern was similar to that seen in pNTs. Phox2b IHC was highly sensitive and specific for detecting ganglion cells. It worked especially well for immature ganglion cells, seen in premature neonates, and scattered single forms in transition zones. In basic research settings, Phox2b can be a useful marker for early differentiation of ENCCs.

Distribution of segmental chromosomal alterations in neuroblastoma.

Neuroblastoma (NB) is a heterogeneous tumor with extremely diverse prognosis according to clinical and genetic factors such as specific combinations of chromosomal imbalances. Molecular karyotyping data from a national neuroblastic tumor database of 155 NB samples were analyzed and related to clinical data. Segmental chromosomal alterations (SCA) were detected in 102 NB, whereas 45 only displayed numerical alterations. Incidence of SCA was higher in stage M (92%) and MYCN amplified (MNA) NB (96%). Presence of SCA was associated with older age, especially 1q gain and 3p deletion. 96% of the deaths were observed in the SCA group and 85% of the relapsed NB contained SCA. The alteration most commonly associated with a higher number of other segmental rearrangements was 11q deletion, followed by 4p deletion. Whole-chromosome 19 gain was associated with lower stages, absence of SCA and better outcome. SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.

Retrospective accuracy analysis of MRI based lesion size measurement in neuroblastic tumors: which sequence should we choose?

BackgroundMR imaging of neuroblastic tumors is widely used for assessing the effect of chemotherapy on tumor size. However, there are some concerns that MRI might falsely estimate lesion diameters due to calcification and fibrosis. Therefore, the aim of our study was to compare neuroblastic tumor size based on MRI measurements to histopathology measurements of the resected specimens as standard of reference.MethodsInclusion criteria were diagnosis of a neuroblastic tumor, MR imaging within 100 days to surgery and gross total resection without fragmentation of the tumor between 2008 and 2019. Lesion diameters were measured by two radiologists according to RECIST 1.1 in axial plane in T2w turbo spin echo (TSE), diffusion-weighted imaging (DWI), and in T1w pre- and postcontrast sequences. Furthermore, the largest lesion size in three-dimensions was noted. The largest diameter of histopathology measurements of each specimen was used for comparison with MRI.ResultsThirty-seven patients (mean age: 5 ± 4 years) with 38 lesions (neuroblastoma: n = 17; ganglioneuroblastoma: n = 11; ganglioneuroma: n = 10) were included in this retrospective study. There was excellent intra-class correlation coefficient between both readers for all sequences (> 0.9) Tumor dimensions of reader 1 based on axial MRI measurements were significantly smaller with the following median differences (cm): T1w precontrast − 1.4 (interquartile range (IQR): 1.8), T1w postcontrast − 1.0 (IQR: 1.9), T2w TSE: -1.0 (IQR: 1.6), and DWI -1.3 (IQR: 2.2) (p < 0.001 for all sequences). However, the evaluation revealed no significant differences between the three-dimensional measurements and histopathology measurements of the resected specimens regardless of the applied MRI sequence.ConclusionsAxial MRI based lesion size measurements are significantly smaller than histopathological measurements. However, there was no significant difference between three-dimensional measurements and histopathology measurements of the resected specimens. T2w TSE and T1w postcontrast images provided the lowest deviation and might consequently be preferred for measurements.

The Treatment of Opsoclonus-Myoclonus Syndrome Secondary to Neuroblastic Tumours-Single-Centre Experience and Literature Review.

Background and Objectives: The opsoclonus-myoclonus syndrome (OMS) is characterised by opsoclons, myoclons and impaired balance, often concomitant with sleep disorder and behavioural difficulties. The symptoms develop as a result of autoimmune response triggered by a neuroblastic tumour (NT). OMS can also develop secondarily to a viral infection or as an immune response triggered by an unknown agent. This leads to the activation of B- and T-cells, which produce and release autoantibodies or cytokines directly within the central nervous system (CNS), thus damaging the neurons within the cerebellum and the brain stem. The available OMS treatments aim at decreasing lymphocyte, cytokine and autoantibody production or accelerating the utilisation of the latter. Another treatment option for OMS involves using cytostatic agents, which damage T- and B-cells causing their depletion and impaired function, which reduces their ability to produce antibodies and cytokines. Materials and Methods: We present a single-centre experience in treating OMS secondary to NT in 7 children. Results: The combined treatment with cyclophosphamide plus dexamethasone resulted in a complete resolution of OMS symptoms in 4 children, and a significant improvement in the 3 children. Two of them periodically present hyperactivity, and one girl requires an additional support at school due to special educational needs (SEN). Conclusions: NT resection does not resolve OMS in children with OMS secondary to NT. The combined treatment with dexamethasone plus cyclophosphamide seems to be an effective treatment of OMS.

AQP2 as a diagnostic immunohistochemical marker for pheochromocytoma and/or paraganglioma.

Aquaporin2 (AQP2) is water channel protein that is widely distributed among mammalian tissues and plays a major role in water homeostasis. However, little is known about the expression and significance of AQP2 in human adrenal tumors. Thus, we performed an immunohistochemical investigation of AQP2 in normal and neoplastic adrenal tissues. AQP2 protein expression was investigated in 190 adrenal tumor patients using immunohistochemistry. Correlation between protein expression and clinicopathological features was statistically analyzed. We demonstrated immunopositivity for AQP2 in all adrenal medulla-originating tumors, including 96 pheochromocytomas (PCC), 7 metastatic pheochromocytomas (MPCC), and 10 neuroblastic tumors (NT) and 13 extra-adrenal paragangliomas (EAPGL). Whereas, APQ2 was absent from the 52 adrenal cortical adenomas and 2 adrenal cortical carcinomas examined. The 10 metastatic carcinomas examined in adrenal tissue were also negative for AQP2. In 82 (85%) of the 96 samples from patients with PCC, we studied the relationship between clinicopathologic factors and AQP2 expression and our findings suggested that the tumors that exhibited diffuse expression pattern of AQP2 were larger in diameter than those exhibiting focal (P=0.007) or mediate expression pattern (P=0.001). AQP2 protein is significantly expressed in normal adrenal medullary tissues and medullary tumors (including PCC, MPCC and NT) as well as EAPGL. AQP2 expression may indicate the origin of normal adrenal tissues, and its expression in cancer tissue may reflect the maintenance of water metabolism via AQP2 during tumorigenesis. AQP2 may serve as a valuable marker for the differential diagnosis of adrenal tumors.

Non-invasive prediction of an unfavorable histological variant in patients with neuroblastic tumors using the quantitative and semiquantitative assessment of ¹²³I-MIBG uptake

¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy is widely used for the detection and staging of neuroblastoma. Risk-adapted treatment in patients with neuroblastic tumors is based on many clinical and genetic factors including histopathology. Purpose: non-invasive prediction of an unfavorable histological variant in patients with neuroblastic tumors using quantitative assessment of ¹²³I-MIBG uptake. This study was approved by the Independent Ethical Committee and the Academic Council of Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation. 96 patients were included in this retrospective study. ¹²³I-MIBG-scintigraphy including whole body planner images and SPECT/CT were performed for all patients before any type of treatment. Semiquantitative and quantitative assessment of ¹²³I-MIBG uptake were calculated and analyzed. Out of 96 patients: 54 with neuroblastoma (NB), 28 with ganglioneuroblastoma (GNB) and 14 with ganglioneuroma (GN). The average values of TLCRR and SUVmax for NB were 5.67 and 7.5, for GNB – 2.58 and 3.1 and for GN – 1.48 and 1.85, respectively. A centile analysis was carried out for all groups. SPECT/CT in combination with modern software allows semiquantitative and quantitative assessment of ¹²³I-MIBG uptake in neuroblastic tumor. The TLCRR and SUVmax can be used separately as well as in combination with NSE for prediction of histological variant.

Pediatric neuroblastic tumors: A critical evaluation of cytomorphological features for risk stratification on aspiration cytology.

Neuroblastic tumor (NT) is the most common extracranial solid tumor of childhood with variable outcome which again depends on risk stratification related to distinct biology of the tumor. The use of fine-needle aspiration (FNA) material for evaluation of cytomorphological parameters and risk stratification in NTs using cytology prognostic score (PS) is limited in routine practice. We reviewed 38 FNA cytology cases diagnosed as pediatric small round cell tumor between time period June 2017 to December 2019 for clinical, cytomorphological and immunohistochemical features. Ten out of 38 small round cell tumors were NTs. All 10 cases were further subclassified according to International Neuroblastoma Pathology Classification into undifferentiated neuroblastoma (n = 1), poorly differentiated neuroblastoma (n = 5), differentiating neuroblastoma (n = 2), and ganglioneuroblastoma (n = 2). Cytologic PS was done using the morphological criteria as described previously in literature. The patients were divided into favorable and unfavorable cytomorphological prognostic categories with a cut off scoring of 12. A score of more than 12 is associated with high risk morphology and advanced stage. All cases with PS > 12 (n-4) (unfavorable cytomorphology) had a poor outcome compared to six patients with PS < 12 (n-6) (favorable cytomorphology). Aspiration cytology can be used as a first line investigation to evaluate the cytomorphological features for risk stratification and diagnosis in patients with NTs using cytological prognostic scoring system. A larger multi-centric validation study necessitates for cytological risk stratification.

The Clinical Management and Outcomes of Pelvic Neuroblastic Tumors

BackgroundPelvic neuroblastomas are rare and often present in children as massive tumors whose surgical resection can be associated with significant morbidity, given sacral nerve root involvement and close proximity to pelvic vascular structures. We sought to examine the characteristics of patients with pelvic neuroblastoma and the effect of extent of surgical resection on survival and surgical outcomes. Materials and methodsAfter institutional review board approval, a retrospective chart review was performed at Children's Hospital Los Angeles from 2000 to 2018. Collected data included tumor location, size, image-defined risk factors histology, stage and risk classification, amplification of the oncogene MYCN or N-myc, use of preoperative chemotherapy, and extent of surgical resection. Outcome variables included postoperative complications and survival. ResultsTen patients with primary pelvic neuroblastoma tumors were identified. The median age at diagnosis was 4.2 y (3 mo to 11 y). Four patients presented with a localized pelvic tumor (stage I or stage II) and underwent upfront tumor resection. Six patients presented with advanced disease (stage III or stage IV) and underwent neoadjuvant chemotherapy, followed by partial resection (30%-90% debulked). One patient experienced a complication: lower extremity hypotonia after tumor resection. One patient died from extensive metastatic disease for which no resection was attempted. The mean postoperative follow-up was 3.9 y with 90% overall survival. ConclusionsOur data show that patients who undergo gross total resection for localized pelvic neuroblastoma or neoadjuvant chemotherapy, followed by partial resection for advanced disease have excellent survival. We recommend that small localized pelvic neuroblastoma undergo gross total resection and large unresectable tumors undergo neoadjuvant chemotherapy, followed by partial debulking resection to avoid neurovascular morbidity.

末梢性神経芽腫群腫瘍の病理：Precision Medicineを含めた最新の話題

末梢性神経芽腫群腫瘍の病理：Precision Medicineを含めた最新の話題

Abordagem Cirúrgica Realizada em 3 Tempos

Ganglioneuromas são tumores neuroblásticos, derivados da crista neural. Raros, afetam crianças e adultos jovens, com predileção pelo sexo feminino e majoritariamente de comportamento benigno e assintomático. Originam-se em qualquer parte do sistema simpático paravertebral, tendo o interior da cavidade torácica e o retroperitônio como principais sítios, com raro acometimento simultâneo. Objetivo: Elucidar a complexidade da abordagem de lesões tumorais que ultrapassam diferentes planos anatômicos, propondo uma estratégia cirúrgica inovadora. Métodos: Este relato de caso baseou-se em coleta de dados do prontuário de uma paciente em acompanhamento no ambulatório de neurocirurgia no Hospital Escola Álvaro Alvim. Resultados: Obteve-se, através de uma técnica minimamente invasiva, excisão em bloco do tumor, com margens de segurança, do componente abdominal, e ressecção parcial da porção das raízes nervosas lombares. Conclusão: Os tumores das raízes lombares com progressão para a cavidade abdominal exigem abordagem multiprofissional, devido à necessidade de disjunção dos segmentos da lesão em etapas. Admite-se que, com o domínio da técnica cirúrgica, os tumores benignos devem ser removidos imperiosamente pela via videolaparoscópica, devido às vantagens em relação à morbidade e recuperação pós-operatória se comparada à laparotomia.

CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours.

BackgroundNeuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression.MethodsWe have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts.FindingsWe show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation.InterpretationWe describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer.FundingResearch supported by grants from the “Asociación Española contra el Cáncer” (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).

The ganglioside GD2 as a circulating tumor biomarker for neuroblastoma.

GD2 is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma and is shed into the circulation. GD2 was measured with a high-pressure liquid chromatography/tandem mass spectrometry assay in serum or plasma from 40 children without cancer (controls) and in biobanked samples from 128 (73 high-risk) children with neuroblastic tumors at diagnosis, 56 children with relapsed neuroblastoma, 14 children with high-risk neuroblastoma after treatment, and 8 to 12 children each with 10 other common childhood cancers at diagnosis. The C18 (18 carbon fatty acid) lipoform was the predominant circulating form of GD2 in controls and in patients with neuroblastoma. The median concentration of GD2 in children with high-risk neuroblastoma at diagnosis was 167nM (range, 16.1-1060nM), which was 30-fold higher than the median concentration (5.6nM) in controls. GD2 was not elevated in serum from children with the differentiated neuroblastic tumors, ganglioneuroma (n=10) and ganglioneuroblastoma-intermixed subtype (n=12), and in children with 10 other childhood cancers. GD2 concentrations were significantly higher in serum from children with MYCN-amplified tumors (P=0.0088), high-risk tumors (P<0.00001), International Neuroblastoma Staging System (INSS) stage 4 tumors (P<0.00001), and in children who died (P=0.034). Circulating GD2 appears to be a specific and sensitive tumor biomarker for high-risk/high-stage neuroblastoma and may prove to be clinically useful as a diagnostic or prognostic circulating tumor biomarker. GD2 will be measured prospectively and longitudinally in children enrolled on a high-risk neuroblastoma treatment trial to assess its ability to measure response to treatment and predict survival.

Clinical analysis of head and neck neurogenic tumor in childhood

Objective:To investigate the clinical characteristics, imaging features and treatment of neurogenic tumor in chilehood and to improve the experience in diagnosis and treatment for the disease. Method:The twenty-nine inpatients of histopathologically proven neurogenic tumor from January 2015 to December 2018 were retrospectively analyzed. The pathological types, clinical characteristics, imaging findings, and management were analyzed. Result: There were five cases of schwannoma aged from 9 years to 14 years, five cases of neurofibroma aged from 9 months to 9 years, and nineteen cases of neuroblastic tumor aged from 3 months to 5 years in our series. The chief manifestations were soft tissue masses, snore, and Honer syndrome. As the tumors had different components pathologically, on scans they presented as masses with heterogeneous density. Schwannoma showed as oval masses with clear margins, with the characteristic of"tail sign". The imaging findings of neurofibromas showed unclear boundaries and plexiform neurofibromas showed multiple clumps with visible separation. The ultrasonography of neuroblastic tumor was characterized by hypoechoic, heterogeneous and spotty calcification. All the cases underwent surgical resections. In 5 cases of schwannoma, it was confirmed that the tumors originated from the vagus nerve during the operation, which could be completely removed without postoperative complications. Two cases of neurofibromas were completely resected, 2 cases were only partially resected, and 1 case which located at the entrance of the esophagus was resected under supportive laryngoscopic for three times. Thirteen of 19 children with neuroblastogenic tumors underwent resection in our department after chemotherapy, and 2 patients with postoperative recurrence underwent another operation. Conclusion:Neuroblastoma is the most common neurogenic tumor in the head and neck of children. Most neurogenic tumors have their corresponding characteristics on imaging and should be differentiated. Schwannoma has clear boundary and intact capsule, so it is easier to complete resection. The neurofibroma is commonly difficult to remove with safety margin because of its unclear boundaries. Neuroblastoma should be treated according to the lesion range and stage. Most of the lesions are difficult to remove completely due to the wide range, peripheral blood vessels and important nerves. So preoperative chemotherapy is generally required.

Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors.

It is still unclear what drives progression of childhood tumors. During Drosophila larval development, asymmetrically-dividing neural stem cells, called neuroblasts, progress through an intrinsic temporal patterning program that ensures cessation of divisions before adulthood. We previously showed that temporal patterning also delineates an early developmental window during which neuroblasts are susceptible to tumor initiation (Narbonne-Reveau et al., 2016). Using single-cell transcriptomics, clonal analysis and numerical modeling, we now identify a network of twenty larval temporal patterning genes that are redeployed within neuroblast tumors to trigger a robust hierarchical division scheme that perpetuates growth while inducing predictable cell heterogeneity. Along the hierarchy, temporal patterning genes define a differentiation trajectory that regulates glucose metabolism genes to determine the proliferative properties of tumor cells. Thus, partial redeployment of the temporal patterning program encoded in the cell of origin may govern the hierarchy, heterogeneity and growth properties of neural tumors with a developmental origin.

Clinical Features of Neuroblastoma with 11q Deletion: An Increase in Relapse Probabilities in Localized and 4S Stages

Neuroblastoma (NB) is a heterogeneous tumor with an extremely diverse prognosis according to clinical and genetic factors, such as the presence of an 11q deletion (11q-del). A multicentric study using data from a national neuroblastic tumor database was conducted. This study compared the most important features of NB patients: presence of 11q-del, presence of MYCN amplification (MNA) and remaining cases. A total of 357 patients were followed throughout an 8-year period. 11q-del was found in sixty cases (17%). 11q-del tumors were diagnosed at an older age (median 3.29 years). Overall survival (OS) was lower in 11q-del patients (60% at 5 years), compared to all other cases (76% at 5 years) p = 0.014. Event free survival (EFS) was 35% after 5 years, which is a low number when compared with the remaining cases: 75% after 5 years (p < 0.001). Localized tumors with 11q-del have a higher risk of relapse (HR = 3.312) such as 4 s 11q-del patients (HR 7.581). 11q-del in NB is a dismal prognostic factor. Its presence predicts a bad outcome and increases relapse probability, specially in localized stages and 4 s stages. The presence of 11q aberration should be taken into consideration when stratifying neuroblastoma risk groups.