Peripheral Neuroblastic Tumors Research Articles

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

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. Fifty-nine adults and adolescents (aged over 15years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied. 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 24years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%). 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.

A Preliminary Study on the Application of Contrast-Enhanced Ultrasonography in Children With Peripheral Neuroblastic Tumors

The purpose of this study was to retrospectively analyze the characteristics of contrast-enhanced ultrasound (CEUS) images and quantitative parameters of time-intensity curves (TICs) in children's peripheral neuroblastic tumors (pNTs). By comparing the imaging features and quantitative parameters of the TICs of neuroblastoma (NB) and ganglioneuroblastoma (GNB) patients, we attempted to identify the distinguishing points between NB and GNB. A total of 35 patients confirmed to have pNTs by pathologic examination were included in this study. Each child underwent CEUS with complete imaging data (including still images and at least 3 min of video files). Twenty-four patients were confirmed to have NB, and 11 were considered to have GNB according to differentiation. The CEUS image features and quantitative parameters of the TICs of all lesions were analyzed to determine whether there were CEUS-related differences between the two types of pNT. There was a significant difference in the enhancement patterns of the CEUS features (χ2 = 5.303, p < 0.05), with more “peripheral-central” enhancement in the NB group and more “central-peripheral” enhancement in the GNB group. In the TIC, the rise time and time to peak were significantly different (p < 0.05). The receiver operating characteristic curve showed that the probability of ganglion cell NB increased significantly after RT > 15.29, with a sensitivity of 0.636 and a specificity of 0.958. When the peak time was greater than 16.155, the probability of NB increased significantly, with a sensitivity of 0.636 and a specificity of 0.958. The CEUS features of NB and GNB patients are very similar, and it is difficult to distinguish them. Rise time and time to peak may be useful in identifying GNB and NB, but the sample size of this study was small, and the investigation was only preliminary; a larger sample size is needed to support these conclusions.

Current vaccination status and safety of children with peripheral neuroblastoma in the real-world.

peripheral neuroblastic tumors (pNT) have high incidence and mortality, and infants are prone to various infectious diseases. The purpose of this study is to understand the immunization status of children with pNT in the real-world and the incidence of adverse reactions after vaccination, and to evaluate the feasibility of vaccination and the influencing factors of vaccination. Children with pNT treated in the Children's Hospital Affiliated to Zhejiang University from January 1, 2011 to December 1, 2021 were included. By referring to medical records, the vaccination history of the national immunization program (NIP) vaccines and the occurrence of adverse events following immunization(AEFI), current status and safety of immunization in children with pNT in the real-world were analyzed. Among 784 children with pNT, 394 were able to obtain the history of vaccination. The overall vaccination rate of NIP vaccines was 71.49% before chemotherapy and 37.67% after chemotherapy, and the recovery time of vaccination after treatment was 16.00 (6.00,24.00) months. Age, time of tumor diagnosis and disease classification were significantly correlated with vaccination. AEFI reported an incidence of 0.23‰. The vaccination rate of children with pNT is generally low, especially the vaccination rate after chemotherapy. The vaccination safety is good, children should be encouraged to immunize.

Extremely high prognostic risk group of neuroblastic tumors: histological, immunophenotypic and genetic characteristics. Literature review and own observations

Clinical heterogeneity appears to be one of the most characteristic feature of the group of peripheral neuroblastic tumors, ranging from spontaneous tumor regression to a widespread process, often resistant to multimodal therapeutic strategies. Despite significant progress in treatment, about 40 % of patients with high-risk neuroblastoma die from disease recurrence after complete response to first-line therapy. These 40 % are considered a “extremely high” risk group requiring intensification of therapeutic regimens from the time of diagnosis. Histological and molecular predictive features of this group are of high scientific and practical interest for the correct therapy.

Computed tomography-based radiomics to assess risk stratification in pediatric malignant peripheral neuroblastic tumors.

This study aimed to develop and validate an analysis system based on preoperative computed tomography (CT) to predict the risk stratification in pediatric malignant peripheral neuroblastic tumors (PNTs). A total of 405 patients with malignant PNTs (184 girls and 221 boys; mean age, 33.8 ± 29.1 months) were retrospectively evaluated between January 2010 and June 2018. Radiomic features were extracted from manually segmented tumors on preoperative CT images. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were used to eliminate redundancy and select features. A risk model was built to stratify low-, intermediate-, and high-risk groups. An image-defined risk factor (IDRFs) model was developed to classify 266 patients with malignant PNTs and one or more IDRFs into high-risk and non-high-risk groups. The performance of the predictive models was evaluated with respect to accuracy (Acc) and receiver operating characteristic (ROC) curve, including the area under the ROC curve (AUC). The risk model demonstrated good discrimination capability, with an area under the curve (AUC) of 0.903 to distinguish high-risk from non-high-risk groups, and 0.747 to classify intermediate- and low-risk groups. In the IDRF-based risk model with the number of IDRFs, the AUC was 0.876 for classifying the high-risk and non-high-risk groups. Radiomic analysis based on preoperative CT images has the potential to stratify the risk of pediatric malignant PNTs. It had outstanding efficiency in distinguishing patients in the high-risk group, and this predictive model of risk stratification could assist in selecting optimal aggressive treatment options.

Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population

Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population

Peripheral neuroblastic tumors in childhood

Peripheral neuroblastic tumors represent the fourth-largest group of malignant tumors in childhood. The majority of these tumors are neuroblastomas, which can be classified into undifferentiated, poorly differentiated, and differentiating subtypes. In addition, peripheral neuroblastic tumors include ganglioneuroblastoma, acomposite tumor composed of Schwannian cell stroma and neuroblasts as well as benign ganglioneuroma. In this overview, histopathological diagnostic criteria and grading systems, as well as common molecular alterations that are of prognostic and therapeutic significance, are discussed.

Ganglioneuromas in Childhood: Hacettepe Experience With 70 Cases

BackgroundGanglioneuromas (GNs) are rare benign peripheral neuroblastic tumors (PNTs). We shared our institutional experience with childhood GNs. MethodsRecords of the children with PNTs between January 1995 and December 2021 were reviewed, and cases with histopathological diagnoses of GN were identified. Clinical, laboratory, radiological, and histopathological findings, image-defined risk factors (IDRFs), procedures, and overall outcomes were recorded. ResultsOf 668 cases with PNTs, 70 (10.4%) had GNs. The median age was 7.4 years (range, 2.6–15.7 years) (girls/boys, 41/29). Common presenting complaints were abdominal pain and cough; 33/70 cases (47.1%) were diagnosed incidentally. Primary tumors were in the abdomen in 41/70, the thorax in 25/70, the neck in 3 cases, and the pelvis in one. The median tumor size was 6.5 cm (range, 1.4–17). Fifty cases (71.4%) were staged as INRG-L1; 20 cases with IDRFs (15 single, five >1) were staged as INRG-L2. Complete and partial tumor resections were performed in 58/70 and 6/70 cases, while 6 had no resection. The overall complication rate was 17.1% (11/64). At a median follow-up of 9 years, five were lost to follow-up; 65 were alive. One patient with gross residue underwent total resection due to progression 13 years after the surgery, and one in the unresected group was lost to follow-up. Ten other cases without a complete resection experienced no tumor progression. ConclusionsGanglioneuromas are benign PNTs, and most are free of IDRFs. Even without complete resection, long-term outcomes are excellent. Guidelines should be devised considering the high surgical complication rates and benign course of GNs. Level of EvidenceCase series, IV.

Maturation of metastases in peripheral neuroblastic tumors (neuroblastoma) of children.

Peripheral neuroblastic tumors of childhood exhibit 3 principal neural crest lineages: primitive neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. They are unique in undergoing maturation of neurons (ganglion cells) and Schwann cells, thereby recapitulating normal fetal neuronal development in the brain. Precision in estimating neurogenesis is enhanced by immunoreactivities of markers of neuronal maturation. Whether organ tissue factors in different sites of metastases influence rates of maturation and whether metastases are similar to their primary neuroblastic tumor are incompletely documented. Four young children, 1 with a mixed primary adrenal tumor and 3 with metastases were studied at surgery or autopsy. Immunocytochemical reactivities included microtubule-associated protein-2, synaptophysin, chromogranin-A, somatostatin, keratan sulfate, vimentin, S-100β protein, and PHOX2B. Primary tumors were non-uniform with regions of either poor or enhanced maturation. Both neuronal and Schwannian lineages were represented in each tumor type but differed in proportions. Bi- or multi-nucleated ganglion cells matured equal to mononuclear forms. Ganglion cell maturation was similar in metastases regardless of the target organ. Metastases resembled primary tumors. Immunocytochemical markers of neuronal and of Schwann cell maturation provide greater diagnostic precision to supplement histological criteria. Interval between diagnosis of primary tumor and metastases, metastatic target tissues, and chemotherapy over an interval of time do not appear to influence neuroblastic or Schwann cell differentiation.

1041 Recurrent Retropharyngeal Ganglioneuroma in a Pediatric Patient

Abstract Introduction Ganglioneuroma is a rare benign subtype of peripheral neuroblastic tumor that arises from sympathetic ganglion cells. Fewer than 10% of these cases occur in the head and neck and are rarely seen in pediatric patients. Clinical symptoms and treatment are dependent on mass location and extension. The authors present a case of recurrent retropharyngeal ganglioneuroma in a pediatric patient. Report of case(s) Patient is a 2-year-old previously healthy female who presented with progressive snoring and found to have retropharyngeal lymphadenopathy during tonsillectomy. Differential diagnosis included retropharyngeal abscess; however, after no improvement with antibiotics, malignancy was suspected. Pathology results from a needle biopsy confirmed the diagnosis of ganglioneuroma. CT imaging showed extension of mass to bilateral retropharyngeal, posterior mediastinal and paraspinal, and retroperitoneal spaces. Given concerns for significant morbidity with complete resection, patient underwent partial resection of mass, followed by chemotherapy to decrease tumor burden. Patient initially did well, then developed nine-month progressive snoring, positional apnea, persistent stertor, and dysphagia. Sleep study showed severe obstructive sleep apnea (OSA) with apnea hypopnea index (AHI) 74, oxygen nadir 66%, and maximum transcutaneous carbon dioxide (CO2) level of 58 mmHg. Repeat CT imaging showed regrowth of the tumor with large right-sided retropharyngeal mass, mass effect on right oropharynx and associated vasculature, and moderate narrowing of airway. Supplemental oxygen via nasal cannula was initiated as inpatient, due to concerns that noninvasive positive pressure support would further compromise the critical airway. Urgent repeat debulking of the tumor with partial pharyngectomy was completed. Post-operatively, patient's oxygen dependence, stertor, and positional apnea resolved within 24 hours. Repeat sleep study showed considerable improvement with mild OSA, AHI 1.4, oxygen nadir 89%, and maximum transcutaneous CO2 level of 47 mmHg. Her dysphagia and residual mild intermittent snoring are improving with no signs of recurrence of the mass. Conclusion Upper airway obstruction secondary to neck mass in pediatric patients is rare and even less commonly found to be recurrent ganglioneuroma. This case offers further understanding of the complexities of diagnosing and treating insidiously growing retropharyngeal tumors and the prompt management of critically obstructed airways. Support (if any)

Pediatric opsoclonus myoclonus ataxia syndrome in the setting of COVID-19 (P5-9.010)

<h3>Objective:</h3> To describe peri-infectious opsoclonus myoclonus ataxia syndrome (OMAS) in the setting of COVID-19 infection in children. <h3>Background:</h3> OMAS is well described in pediatric patients with peripheral neuroblastic tumors and less defined in the setting of peri-infectious etiologies such as SARS-CoV-19 which is better appreciated in adults. <h3>Design/Methods:</h3> We describe two separate cases of peri-infectious COVID-19 OMAS in pediatric patients at a tertiary Children’s Hospital in 2022, both previously healthy female patients, 2 years and 18 months of age. <h3>Results:</h3> Patient A is a two year-old female who initially presented with ataxia in context of acute COVID-19 infection at 16 months of age and later developed abnormal eye movements, myoclonus and irritability with multiple relapses over a nine month period. Patient B is a 18 month-old female presenting with acute onset abnormal eye movements and ataxia at age 14 months and later developed myoclonic jerks and irritability with sleep disturbance, subsequently found to have COVID-19 antibodies, now with remission of symptoms. Both patients had comprehensive work up for malignancy, toxic-metabolic encephalopathy, structural central nervous system disease, infectious meningoencephalitis and genetic ataxia syndromes. Both were treated with IVIG and high dose steroids. Patient A had subsequent relapses and required escalation of treatment to ACTH. Patient A had a more complicated course which included treatment with acetazolamide and levetiracetam for myoclonus. Her myoclonic jerks demonstrated intermittent electrographic correlates on EEG. <h3>Conclusions:</h3> While OMAS associated with neuroblastic tumors is well described in the pediatric literature, it is less well known in relation to peri-infectious phenomena, particularly SARS-CoV-2 infection in children. Prior published reports of OMAS related to COVID-19 infection in adults indicated a favorable prognosis after initial treatment. However, we present a case with repeated relapses and the need for more aggressive treatment. The present report broadens the phenotypic spectrum for OMAS outside of paraneoplastic etiologies. <b>Disclosure:</b> Dr. Yakir has nothing to disclose. Dr. Most has nothing to disclose. Dr. Hermel has nothing to disclose. Dr. Zimbric has received personal compensation in the range of $0-$499 for serving as a Survey volunteer with Opinionsite. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Sinopia Biosciences. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Pet Dx. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. Dr. Friedman has stock in Friedman Bioventure . Dr. Rho has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nutricia. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. Dr. Rho has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. The institution of Dr. Rho has received research support from National Institutes of Health. Dr. Rho has received publishing royalties from a publication relating to health care.

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

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. To describe the clinicopathological characteristics of extra-adrenal peripheral neuroblastic tumors. Materials and. 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. 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. 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.

18F-FDG PET/CT imaging of pediatric peripheral neuroblastic tumor: a combined model to predict the International Neuroblastoma Pathology Classification

The aim of this study was to evaluate the effect of a model combining a 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics signature with clinical factors in the preoperative prediction of the International Neuroblastoma Pathology Classification (INPC) type of pediatric peripheral neuroblastic tumor (pNT). A total of 106 consecutive pediatric pNT patients confirmed by pathology were retrospectively analyzed. Significant features determined by multivariate logistic regression were retained to establish a clinical model (C-model), which included clinical parameters and PET/CT radiographic features. A radiomics model (R-model) was constructed on the basis of PET and CT images. A semiautomatic method was used for segmenting regions of interest. A total of 1,016 radiomics features were extracted. Univariate analysis and the least absolute shrinkage selection operator were then used to select significant features. The C-model was combined with the R-model to establish a combination model (RC-model). The predictive performance was validated by receiver operating characteristic (ROC) curve analysis, calibration curves, and decision curve analysis (DCA) in both the training cohort and validation cohort. The radiomics signature was constructed using 5 selected radiomics features. The RC-model, which was based on the 5 radiomics features and 3 clinical factors, showed better predictive performance compared with the C-model alone [area under the curve in the validation cohort: 0.908 vs. 0.803; accuracy: 0.903 vs. 0.710; sensitivity: 0.895 vs. 0.789; specificity: 0.917 vs. 0.583; net reclassification improvement (NRI) 0.439, 95% confidence interval (CI): 0.1047-0.773; P=0.01]. The calibration curve showed that the RC-model had goodness of fit, and DCA confirmed its clinical utility. In this preliminary single-center retrospective study, an R-model based on 18F-FDG PET/CT was shown to be promising in predicting INPC type in pediatric pNT, allowing for the noninvasive prediction of INPC and assisting in therapeutic strategies.

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.

Management of a Composite Pheochromocytoma (Pheochromocytoma/Neuroblastoma) in Adult Patient Recurring After Several Years: A Complex Case Report.

Pheochromocytoma/neuroblastoma composite tumors are rare entities for which little is known. We report an atypical case of a 39-year-old man with secondary bone locations of a composite tumor, 7 years after resection of adrenal neuroblastoma, with constitutional alteration of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 whose role is unknown. The diagnosis of a peripheral neuroblastic tumor in adulthood is difficult and even more so when it is a composite tumor. In the absence of a standard of care, management is varied and discussions about treatment modalities for these patients are complex.

ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD.

ObjectiveRapid‐onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), is a severe pediatric disorder of uncertain etiology resulting in hypothalamic dysfunction and frequent sudden death. Frequent co‐occurrence of neuroblastic tumors have fueled suspicion of an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti‐neural autoantibodies, a hallmark of PNS, have not been identified. Our objective is to determine if an autoimmune paraneoplastic etiology underlies ROHHAD.MethodsImmunoglobulin G (IgG) from pediatric ROHHAD patients (n = 9), non‐inflammatory individuals (n = 100) and relevant pediatric controls (n = 25) was screened using a programmable phage display of the human peptidome (PhIP‐Seq). Putative ROHHAD‐specific autoantibodies were orthogonally validated using radioactive ligand binding and cell‐based assays. Expression of autoantibody targets in ROHHAD tumor and healthy brain tissue was assessed with immunohistochemistry and mass spectrometry, respectively.ResultsAutoantibodies to ZSCAN1 were detected in ROHHAD patients by PhIP‐Seq and orthogonally validated in 7/9 ROHHAD patients and 0/125 controls using radioactive ligand binding and cell‐based assays. Expression of ZSCAN1 in ROHHAD tumor and healthy human brain tissue was confirmed.InterpretationOur results support the notion that tumor‐associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of ROHHAD syndrome, thus providing a means toward early detection and treatment. This work warrants follow‐up studies to test sensitivity and specificity of a novel diagnostic test. Last, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human‐based approaches for detecting novel PNS subtypes. ANN NEUROL 2022;92:279–291

Ganglioneuroblastoma in the Retropharyngeal Space: A Case Report and Literature Review.

Ganglioneuroblastoma is a rare peripheral neuroblastic tumor located anywhere in the sympathetic nervous system but rarely in the retropharyngeal space. Diagnosis can often be difficult based on imaging alone. We describe one case of a child presenting with snoring. The lesion was located in the rare retropharyngeal space, and its histology finally revealed ganglioneuroblastoma. Therefore, clinicians should be aware of pediatric patients with respiratory symptoms indicating cervical ganglioneuroblastoma. To make a definite diagnosis as soon as possible, a core needle biopsy or even immunohistochemistry may need to be performed before surgery.

Ganglion cell maturation in peripheral neuroblastic tumours of children.

Peripheral neuroblastic tumours of neural crest origin are the most frequent solid neoplasms outside the CNS in children. Neuroblastoma/ganglioneuroblastoma/ganglioneuroma have a natural evolution of histological differentiation over time. Together with mitosis-karyorrhexis index and patient age (International Neuroblastoma Pathology Classification criteria), ganglion cell maturation determines grading and prognosis. Maturation presently is usually assessed only histologically. Immunocytochemical tissue markers defining neuroblast maturation in fetal CNS were here applied to peripheral neuroblastic tumours arising in the adrenal medulla or sympathetic chain. Paraffin sections of resected tumours of 4 toddlers were examined using antibodies demonstrating neuronal identity and maturation: MAP2; synaptophysin; chromogranin-A; NeuN; keratan sulfate (KS); glutamate receptor antibody (GluR2). Synaptophysin, normally a late marker of neuroblast differentiation, was the earliest expressed in neuroblastoma. Others include: Ki67; S-100β protein; vimentin; nestin; α-B-crystallin; neuroblastoma marker PHOX2B. Various degrees of ganglion cell maturation were demonstrated by MAP2, chromogranin, synaptophysin, KS, and GluR2; NeuN was uniformly negative, consistent with sympathetic neurons. KS was sparsely distributed within the tumours in interstitial tissue, within processes of some non-neuronal cells, and adherent to somata and proximal neuritic trunks. Neoplastic ganglion cells with multiple nuclei matured similar to mono-nuclear forms. PHOX2B did not distinguish maturational stages. S-100β protein and α-B-crystallin labeled Schwann cells, especially Schwannian ganglioneuroma. Immunocytochemical markers of neuroblast maturation in fetal brain also are useful in peripheral neuroblastic tumours, providing greater precision than histology alone. The most practical are MAP2, chromogranin-A, and synaptophysin. Prognosis and choice of treatment including chemotherapy might be influenced.

Spinal Ganglioneuroma

An otherwise healthy 57-year-old man presented with intermittent low back pain and was incidentally found to have a left-sided paraspinal mass invading the spinal canal and causing spinal cord compression. He underwent a T11-12 hemilaminectomy, facetectomy, and instrumented fusion for a gross total resection with a good clinical outcome. Pathology revealed the lesion to be a ganglioneuroma. Ganglioneuroma is a rare and interesting pathology. These tumors are benign peripheral neuroblastic tumors derived from the neural crest and found along the entire neuroaxis. Tumors come to clinical attention if they cause symptomatic compression of neural structures or are found incidentally on imaging. Additionally, as these tumors share a common lineage with pheochromocytomas, systemic symptoms can be observed resulting from secretion of vasoactive peptides. The pathologic diagnosis of ganglioneuroma is predominantly based on morphology.

Diarrhée aqueuse chronique chez l’enfant : une étiologie à ne pas méconnaître

Peripheral neuroblastic tumors are the most common extracranial solid tumors in children. On the other hand, diarrheal neuroblastic tumors are quite rare and not easy to diagnose in the early stage. We report a case of neuroblastic tumor in a 2-year old girl presenting with aqueous diarrhea caused by paraneoplasic secretion of VIP.