Adolescent- and adult-onset neuroblastic tumor: A retrospective multicenter observational study of patients diagnosed in France between 2000 and 2020.

BACKGROUND: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT. PROCEDURE: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied. RESULTS: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%). CONCLUSIONS: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients.

Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements.

Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of TERT-rearranged NTs were further addressed. Genomic TERT rearrangements could be effectively detected by FISH and were mutually exclusive with MYCN amplification. TERT rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. TERT rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, TERT rearrangements were significantly associated with elevated TERT expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating TERT defects, which define a subgroup of NTs with unfavourable prognosis. TERT rearrangements would contribute to characterising NT molecular signatures in clinical practice.

Ganglioneuroblastoma intermixed: Clinicopathological implications of diagnosis at presentation and genomic correlations.

BACKGROUND: Ganglioneuroblastoma intermixed (GNBI) is classified as "favorable" histology by International Neuroblastoma Pathology Classification system. However, the International Neuroblastoma Risk Group (INRG) stratifies patients using wider clinicopathological and cytogenetic/molecular parameters. While the diagnosis of GNBI is typically made on resected tumor, it may sometimes be rendered on initial biopsy. We studied GNBI noted at diagnosis to evaluate its correlation with INRG staging and other clinicopathological and molecular features. METHODS: In this retrospective study, clinical, radiological, pathological, cytogenetic, and molecular information from patients with GNBI at diagnosis seen between 1995 and 2021 was analyzed. INRG staging was performed. RESULTS: Of the 15,827 neuroblastoma specimens, GNBI was noted in 237 patients. Of these, 53 had the initial pathological diagnosis of GNBI; median follow-up 3.5 (range: 0.2-14) years. Disease was locoregional in 41 (77%, 16 stage L1 and 25 L2); none relapsed. Twelve (23%) had metastatic disease at presentation; six (50%) relapsed, and two died of disease. MYCN was amplified in two metastatic tumors. Six of 31 (19%) tumors tested had recurrent cytogenetic abnormalities and nonrecurrent somatic gene mutations in 10/23 (43%). The presence of any adverse molecular/cytogenetic findings was associated with metastatic disease (p < .05). For patients with localized GNBI undergoing both biopsy and resection, GNBI was diagnosed in both in 17/19 (90%). CONCLUSIONS: Localized GNBI at diagnosis has excellent long-term clinical outcome even without cytotoxic therapy. For localized GNBI, a biopsy sample is adequate to make the diagnosis. When associated with metastasis at diagnosis, prognosis is poorer, possibly due to associated adverse biological features.

Extra-adrenal peripheral neuroblastic tumors: A clinicopathological study of 18 cases.

Background: Peripheral neuroblastic tumors arise from the sympathoadrenal lineage of the neural crest. They have been classified according to the International Neuroblastoma Pathology Committee (INPC) into Four categories according to International Neuroblastoma Pathology Committee (INPC): a) Neuroblastoma (NB) b) Ganglioneuroblastoma (GNB), nodular c) Ganglioneuroblastoma, intermixed, and d) Ganglioneuroma (GN). Because of the rarity of extra-adrenal peripheral neuroblastic tumors, limited information is available regarding the chemotherapy of NB and GNB. A few case reports or case series with a small number of patients have been documented in the literature. Aim: To describe the clinicopathological characteristics of extra-adrenal peripheral neuroblastic tumors. Materials and. Methods: Clinical, histopathological, and immunohistochemistry (IHC) findings of 18 cases were retrieved. Immunohistochemistry at the time of diagnosis was performed using Ventana Benchmark XT. The mean value was calculated using the Microsoft Office Excel 2019 software. Results: The posterior mediastinum was the most commonly affected extra-adrenal site in our study. Neuroblastoma consisted of eight cases (six in children, two in adults), of which four cases were poorly differentiated and the other four cases were differentiating. Two cases had favorable histology. The bone marrow and cervical lymph node metastasis were documented. Of the four GNB cases, one patient developed bone metastasis. All patients of NB and GNB received combination chemotherapy. One out of six GN patients presented with a large retroperitoneal mass encasing the aorta and renal vessels, mimicking a sarcoma. Conclusion: Extra-adrenal peripheral neuroblastic tumors do not pose any diagnostic issue in adequate tissue sampling. In limited material, immunohistochemistry is needed. The chemotherapy regimen has not been standardized due to rarity. Further molecular testing and targeted therapy may be of help in the future.

Whole-tumor radiomics analysis of T2-weighted imaging in differentiating neuroblastoma from ganglioneuroblastoma/ganglioneuroma in children: an exploratory study.

PURPOSE: To examine the potential of whole-tumor radiomics analysis of T2-weighted imaging (T2WI) in differentiating neuroblastoma (NB) from ganglioneuroblastoma/ganglioneuroma (GNB/GN) in children. MATERIALS AND METHODS: This study included 102 children with peripheral neuroblastic tumors, comprising 47 NB patients and 55 GNB/GN patients, which were randomly divided into a training group (n = 72) and a test group (n = 30). Radiomics features were extracted from T2WI images, and feature dimensionality reduction was applied. Linear discriminant analysis was used to construct radiomics models, and one-standard error role combined with leave-one-out cross-validation was used to choose the optimal radiomics model with the least predictive error. Subsequently, the patient age at initial diagnosis and the selected radiomics features were incorporated to construct a combined model. The receiver operator characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve (CIC) were applied to evaluate the diagnostic performance and clinical utility of the models. RESULTS: Fifteen radiomics features were eventually chosen to construct the optimal radiomics model. The area under the curve (AUC) of the radiomics model in the training group and test group was 0.940 [95% confidence interval (CI) 0.886, 0.995] and 0.799 (95%CI 0.632, 0.966), respectively. The combined model, which incorporated patient age and radiomics features, achieved an AUC of 0.963 (95%CI 0.925, 1.000) in the training group and 0.871 (95%CI 0.744, 0.997) in the test group. DCA and CIC demonstrated that the radiomics model and combined model could provide benefits at various thresholds, with the combined model being superior to the radiomics model. CONCLUSION: Radiomics features derived from T2WI, in combination with the age of the patient at initial diagnosis, may offer a quantitative method for distinguishing NB from GNB/GN, thus aiding in the pathological differentiation of peripheral neuroblastic tumors in children.

Evaluation of Ki-67 as prognostic factor for pediatric neuroblastoma and the possibility of molecular-targeted drugs with VEGF and PDGFR.

BACKGROUND: Neuroblastoma (NB) is a pediatric malignant solid tumor characterized as refractory cancer with poor prognosis. The Mitosis-Karyorrhexis Index (MKI) is a prognostic factor but is prone to observer bias. The usefulness of MKI with Ki-67, as a marker of malignancy, was investigated. The efficacy of molecular-targeted therapeutic agents with fewer side effects in tumors has been studied. Molecular-targeted therapy targets include vascular endothelial growth factor (VEGF), involved in tumor angiogenesis; c-Kit, receptor of Kit/stem cells involved in tumor growth, vasculature, and lymphangiogenesis; platelet-derived growth factor receptor (PDGFR); and B-Raf proto-oncogene, serine/threonine kinase (BRAF), involved in the RAS protein-mediated mitogen-activated protein kinase pathway. Therefore, expression profiles of these factors and growth inhibitory effects of molecular-targeted drugs against NB were investigated. METHODS: Ten frozen NB tissue samples collected from January 1993 to December 2017 were evaluated immunohistochemically for Ki-67 and VEGF. c-Kit, PDGFR, and BRAF expression levels were evaluated using enzyme-linked immunosorbent assays; relationships between these factors and clinicopathological parameters of NB were analyzed. RESULTS: Eight patients with NB showed no amplification of MYCN (MYCN proto-oncogene, bHLH transcription factor). There were two cases of ganglioneuroblastoma (GNB). More NB cells were positive for Ki-67 than for GNB cells. VEGF expression was observed in all NB specimens and was stronger in stage IIB and higher. No BRAF or c-Kit activity was observed; PDGFR activity was greater in NB than in GNB (P=0.02). CONCLUSIONS: Thus, Ki-67 may help evaluate NB malignancy. As the first therapy for NB prevents amplification of MYCN, agents targeting PDGFR as well as VGFG can inhibit NB cell proliferation.

Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.

Peripheral neuroblastic tumors (PNTs) represent a spectrum of neural-crest-derived tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Malignant cells in PNTs are theorized to interconvert between adrenergic/noradrenergic and mesenchymal/neural crest cell states. Here, single-cell RNA-sequencing analysis of 10 PNTs demonstrates extensive transcriptomic heterogeneity. Trajectory modeling suggests that malignant neuroblasts move between adrenergic and mesenchymal cell states via an intermediate state that we term "transitional." Transitional cells express programs linked to a sympathoadrenal development and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature is predictive of poor prognosis compared with adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identifies a similar transitional H3K27-acetylation super-enhancer landscape. Collectively, our study supports the concept that PNTs have phenotypic plasticity and uncovers potential biomarkers and therapeutic targets.

Pathological prognosis classification of patients with neuroblastoma using computational pathology analysis.

Neuroblastoma is the most common extracranial solid tumor in early childhood. International Neuroblastoma Pathology Classification (INPC) is a commonly used classification system that provides clinicians with a reference for treatment stratification. However, given the complex and subjective assessment of the INPC, there will be inconsistencies in the analysis of the same patient by multiple pathologists. An automated, comprehensive and objective classification method is needed to identify different prognostic groups in patients with neuroblastoma. In this study, we collected 563 hematoxylin and eosin-stained histopathology whole-slide images from 107 patients with neuroblastoma who underwent surgical resection. We proposed a novel processing pipeline for nuclear segmentation, cell-level image feature extraction, and patient-level feature aggregation. Logistic regression model was built to classify patients with favorable histology (FH) and patients with unfavorable histology (UH). On the training/test dataset, patient-level of nucleus morphological/intensity features and age could correctly classify patients with a mean area under the receiver operating characteristic curve (AUC) of 0.946, a mean accuracy of 0.856, and a mean Matthews Correlation Coefficient (MCC) of 0.703,respectively. On the independent validation dataset, the classification model achieved a mean AUC of 0.938, a mean accuracy of 0.865 and a mean MCC of 0.630, showing good generalizability. Our results suggested that automatically derived image features could identify the differences in nuclear morphological and intensity between different prognostic groups, which could provide a reference to pathologists and facilitate the evaluation of the pathological prognosis in patients with neuroblastoma.

Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups.

Peripheral neuroblastic tumors (neuroblastoma, ganglioneuroblastoma and ganglioneuroma) are heterogeneous and their diverse and wide range of clinical behaviors (spontaneous regression, tumor maturation and aggressive progression) are closely associated with genetic/molecular properties of the individual tumors. The International Neuroblastoma Pathology Classification, a biologically relevant and prognostically significant morphology classification distinguishing the favorable histology (FH) and unfavorable histology (UH) groups in this disease, predicts survival probabilities of the patients with the highest hazard ratio. The recent advance of neuroblastoma research with precision medicine approaches demonstrates that tumors in the UH group are also heterogeneous and four distinct subgroups-MYC, TERT, ALT and null-are identified. Among them, the first three subgroups are collectively named extremely unfavorable histology (EUH) tumors because of their highly aggressive clinical behavior. As indicated by their names, these EUH tumors are individually defined by their potential targets detected molecularly and immunohistochemically, such as MYC-family protein overexpression, TERT overexpression and ATRX (or DAXX) loss. In the latter half on this paper, the current status of therapeutic targeting of these EUH tumors is discussed for the future development of effective treatments of the patients.

Minimally invasive surgery for neuroblastic tumours: A SIOPEN multicentre study: Proposal for guidelines.

INTRODUCTION: Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. MATERIALS & METHODS: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. RESULTS: A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. CONCLUSIONS: MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.

Characteristics of benign neuroblastic tumors: Is surgery always necessary?

PURPOSE: Ganglioneuroma (GN) and ganglioneuroblastoma-intermixed (GNB-I) represent benign variants of neuroblastic tumors in children; however, differentiating from more aggressive histological variants of GNB including the nodular subtype (GNB-N) prior to resection can be challenging, even with biopsy. Currently, no standard treatment guidelines exist. The purpose of this study was to identify pre-operative characteristics of benign neuroblastic tumors and evaluate outcomes for patients who underwent surgical resection or observation. METHODS: Retrospective chart review of children treated at a single institution between 2009 and 2019 for non-metastatic tumor with a tissue diagnosis of GN, GNB-N or GNB-I. Demographics, imaging, labs, operative details and outcomes were recorded and analyzed. RESULTS: Of 53 patients, 45% were male. The most common tumor location was abdomen (49%), followed by thorax (34%). Forty-five percent had at least one image defined risk factor. Biopsy was performed in 32% (17/53) and upfront surgery in 68% (36/53). Three patients (3/53, 5.6%) with biopsy demonstrating GN tumors were observed due to high surgical risk. Pathology of resected specimens demonstrated GN in 52% (26/50) and GNB-I or GNB-N in 48% (24/50). The majority of GNB tumors (75% (18/24) were GNB-I and 25% (6/24) were GNB-N. Therefore, 88% of the resected tumors were benign spectrum neuroblastic tumors (GN & GNB-I). Seven (7/50, 14%) patients experienced perioperative complication (temporary paralysis, Horner's syndrome, chylothorax, vocal cord paralysis). Recurrence was noted in 1 patient with GN (1/50, 2%) and 3 with GNB-N (3/50, 6%). There were no tumor-related deaths. Patients with GN were older than those with GNB (8.8 years (IQR 6-11.25) vs 5.6 years for GN (IQR 3-7); p = 0.01). GNB tumors were also more likely to have calcifications on imaging (63% vs. 38%, p = .01) and more commonly had MIBG avidity (88% vs 66%, p = .04). There were no significant differences in tumor size or symptoms at presentation. CONCLUSIONS: In children with neuroblastic tumors, older age, CT without tumor calcifications, lack of MIBG avidity, and/or normal urine catecholamines may indicate benign GN. Close observation could be considered for asymptomatic patients meeting these criteria with biopsy-proven GN, with resection reserved for progressive growth or symptom development. However, larger, multicenter studies are needed for further validation. LEVEL OF EVIDENCE: IV.

Primary uterine ectomesenchymoma harboring a DICER1 mutation: case report with molecular analysis.

Ectomesenchymoma is an exceedingly rare biphasic malignant tumor characterized by the presence of mesenchymal and neuroectodermal elements. The majority of patients are infants or children. We describe the first case of this entity diagnosed as a primary uterine tumor. A 72-year-old female presented with post-menopausal bleeding. Dilatation and curettage showed irregular mesenchymal proliferation of uncertain nature. In the hysterectomy specimen, a myxoid spindle cell tumor with areas of skeletal muscle and neural differentiation was found in the uterus, with direct invasion of the small intestine, and biphasic differentiation into rhabdomyosarcoma and ganglioneuroblastoma was unequivocally seen in a lymph node metastasis. The morphological findings were validated by immunohistochemistry. Massive parallel sequencing identified TP53, PTEN, and DICER1 mutations in the tumor. This report describes the presence of ectomesenchymoma in an unusual primary organ and in an uncharacteristic age and presents novel data regarding the genetic characteristics of this tumor.

Association of image-defined risk factors with clinical features, histopathology, and outcomes in neuroblastoma.

BACKGROUND: Clinical, molecular, and histopathologic features guide treatment for neuroblastoma, but obtaining tumor tissue may cause complications and is subject to sampling error due to tumor heterogeneity. We hypothesized that image-defined risk factors (IDRFs) would reflect molecular features, histopathology, and clinical outcomes in neuroblastoma. METHODS: We performed a retrospective cohort study of 76 patients with neuroblastoma or ganglioneuroblastoma. Diagnostic CT scans were reviewed for 20 IDRFs, which were consolidated into five IDRF groups (involvement of multiple body compartments, vascular encasement, tumor infiltration of adjacent organs/structures, airway compression, or intraspinal extension). IDRF groups were analyzed for association with clinical, molecular, and histopathologic features of neuroblastoma. RESULTS: Patients with more IDRF groups had a higher risk of surgical complications (OR = 3.1, p = 0.001). Tumor vascular encasement was associated with increased risk of surgical complications (OR = 5.40, p = 0.009) and increased risk of undifferentiated/poorly differentiated histologic grade (OR = 11.11, p = 0.013). Tumor infiltration of adjacent organs and structures was associated with decreased survival (HR = 8.90, p = 0.007), MYCN amplification (OR = 9.91, p = 0.001), high MKI (OR = 6.20, p = 0.003), and increased risk of International Neuroblastoma Staging System stage 4 disease (OR = 8.96, p < 0.001). CONCLUSIONS: The presence of IDRFs at diagnosis was associated with high-risk clinical, molecular, and histopathologic features of neuroblastoma. The IDRF group tumor infiltration into adjacent organs and structures was associated with decreased survival. Collectively, these findings may assist surgical planning and medical management for neuroblastoma patients.

Primary orbital ganglioneuroblastoma in a child: A case report.

RATIONALE: Ganglioneuroblastoma (GNB) is a transitional tumor of sympathetic origin that has never been described as primarily involving the orbit. Herein we report an extremely rare case of GNB with primary orbital involvement and its treatment strategies. PATIENT CONCERNS: A 9-year-old girl presented with progressive and recurring right orbital mass for 2 years. DIAGNOSIS: Computed tomography (CT) showed a well-defined, well-circumscribed, and homogeneous extraconal soft tissue mass occupying most of the right superior orbital area. Magnetic resonance imaging (MRI) revealed that there was a neoplasm of the right superior orbit molding around the globe with long T1 and T2 signals, and contrast-enhanced MR image showed a heterogeneous enhancement of the mass. Histopathologic examinations were performed after surgery and the characteristics were consistent with a diagnosis of GNB. INTERVENTIONS: Surgery was performed and the mass was completely resected. OUTCOMES: Postoperatively, the patient was on a regular follow-up for 19 months and so far, has had no orbital mass recurrence. LESSONS: Herein we present a rare case of GNB primarily involving the orbit, and the findings showed that GNB could originate from the orbit. The patient underwent surgical tumor resection. The histopathological and immunohistochemical features were consistent with the diagnosis of GNB. For this case, there was no recurrence for 19 months after complete surgical excision of the tumor; however, a regular long-term follow-up is required.

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

BACKGROUND: MR 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. METHODS: Inclusion 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. RESULTS: Thirty-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. CONCLUSIONS: Axial 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.

Central nervous system ganglioneuroblastoma harboring MYO5A-NTRK3 fusion.

Central nervous system (CNS) ganglioneuroblastoma is a rare neuroectodermal neoplasm and little is known about its clinical and biological features. Herein, we report a pediatric case of CNS ganglioneuroblastoma harboring MYO5A-NTRK3 fusion. The patient, a 4-year-old boy, underwent a partial resection of a supratentorial tumor that was histopathologically diagnosed as a CNS ganglioneuroblastoma. Treatment with radiotherapy was started per the St Jude Medulloblastoma 03 (SJMB03) protocol; however, the tumor progressed rapidly and radiotherapy was temporally discontinued. Meanwhile, the patient underwent a second surgery, in which a gross total resection was successfully performed, following which he completed the remaining protocol-based therapy. Although an early focal recurrence was detected for which he received additional radiotherapy and oral temozolomide, the patient remained in complete remission for 14 months after the completion of the treatment. A central pathological review and molecular analysis were performed that revealed a MYO5A-NTRK3 fusion. Interestingly, the MYO5A-NTRK3 fusion has been recurrently detected in melanocytic tumors but not in other types of tumors. Therefore, it can be speculated that our case might partly share tumorigenesis mechanisms with MYO5A-NTRK3-positive melanocytic tumors. In addition, our case may enable an improved understanding of the pathogenesis and clinical features of CNS ganglioneuroblastomas.

Adrenal masses in children: Imaging, surgical treatment and outcome.

BACKGROUND/OBJECTIVE: This study aims to evaluate the current surgical approach to adrenal masses in the pediatric age group. METHODS: We retrospectively analyzed cases that underwent surgery for adrenal masses between 2007 and 2017. Patients were assessed regarding age, sex, primary diagnosis, image defined risk factors (IDRF), surgical treatment method, complications, duration of hospital stay, and follow-up. RESULTS: We examined 50 patients who underwent surgery for adrenal mass (mean age: 4.8 years; range: 5 days-14 years). For IDRF assessment, Ultrasonography was used in 42, Computed Tomography in 36, and Magnetic Resonance Imaging in 36 patients. Lesions were present on the right in 25, left in 21, and bilateral in 4 patients. Histopathological findings were neuroblastoma (n = 29), ganglioneuroma (n = 6), adrenal cortex tumor (n = 5), ganglioneuroblastoma (n = 4), pheochromocytoma (n = 3), cyst (n = 1), and adrenal hematoma (n = 2). Laparotomy was performed on 37 patients, and laparoscopy on 13 patients. None of the cases had any operative complications. CONCLUSION: The crucial factors determining the surgical approach to adrenal masses in pediatric cases are the histopathology of the mass, volume, and IDRF. Minimally invasive procedures could be reliably performed in appropriate cases.

Posterior mediastinal ganglioneuroblastoma in an adolescent: A case report and review.

Ganglioneuroblastoma is an uncommon malignant tumor of the sympathetic nervous system, which is considered a disease of children with the majority of cases in patients less than four years old and it rarely occurs in adults. We encountered a very unusual case of a posterior mediastinal ganglioneuroblastoma that developed in a 17-year-old male adolescent who underwent successful excision of the mediastinal mass and remained stable postoperatively. However, he developed lumbago one year after the surgery. Radiographic findings revealed osteolytic lesions in the lumbar vertebra and histological analysis confirmed bone metastasis of ganglioneuroblastoma. Here, we report the clinical course and present a review of the literature regarding adolescent and adult onset mediastinal ganglioneuroblastoma.

Cytopathological spectrum of peripheral neuroblastic tumours in fine needle aspiration cytology and categorisation as per International Neuroblastoma Pathology Classification.

OBJECTIVE: The aim of this analysis was to describe the cytopathology spectrum of peripheral neuroblastic tumours (NTs) including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN). Feasibility of applying the International Neuroblastoma Pathology Classification (INPC) to further subtype NTs in cytology was evaluated. METHODS: All peripheral NTs reported on fine needle aspiration during 2011-2015 were retrieved and detailed cytomorphological evaluation was performed. Based on INPC criteria, NBs were further categorised as undifferentiated, poorly differentiated and differentiating subtypes. Mitotic-karyorrhectic index was evaluated. Immunocytochemistry on cell blocks was reviewed wherever available. MYCN amplification by fluorescence in situ hybridisation was performed in 11 cases on smears. RESULTS: A total of 90 cases including 83 NBs, six GNB and one GN were evaluated. The age range was 12 days-12 years, with 55 males and 45 females. Both the primary and metastatic locations were aspirated. Applying the INPC criteria, there were 61 poorly differentiated, 14 undifferentiated, eight differentiating NB and six GNB. Immunocytochemistry on cell blocks showed positivity for at least two neuronal markers in NB. Mitotic-karyorrhectic index was high in 63, low in 22 and intermediate in two cases, respectively. MYCN amplification by fluorescence in situ hybridisation was feasible on smears and was amplified in 6 out of 11 cases tested. CONCLUSION: Peripheral NT types including NB, GNB and GN have distinctive cytomorphology. NBs can be further subtyped as undifferentiated, poorly differentiated and differentiating subtypes as per INPC criteria.