Coexistence of Langerhans Cell Histiocytosis and Ganglioneuroblastoma Revealed by 18 F-FDG PET/CT in a Pediatric Patient.

ABSTRACT: Coexistence of Langerhans cell histiocytosis and ganglioneuroblastoma is rare and seldom reported in the literature. A 3-year-old girl with Langerhans cell histiocytosis underwent 18 F-FDG PET/CT imaging for staging, which demonstrated significant 18 F-FDG accumulation in the mandibles. Unexpectedly, a mild hypermetabolic soft mass was detected in the upper retroperitoneum. Results of surgical pathology of the abdominal mass were consistent with ganglioneuroblastoma.

Cervical Ganglioneuroblastoma Diagnosed by 68Ga-DOTATOC PET/CT in a Child with Opsoclonus Myoclonus Syndrome.

We performed a 68Ga-DOTATOC PET/CT scan on a 25-mo-old female patient who presented with opsoclonus myoclonus ataxia syndrome and had negative initial anatomic imaging. The scan showed a somatostatin receptor-overexpressing cervical tumor in favor of a cervical neuroendocrine tumor, with subsequent histopathologic findings of ganglioneuroblastoma.

Identification and validation of radiomic features from computed tomography for preoperative classification of neuroblastic tumors in children.

BACKGROUND: To identify radiomic features that can predict the pathological type of neuroblastic tumor in children. METHODS: Data on neuroblastic tumors in 104 children were retrospectively analyzed. There were 14 cases of ganglioneuroma, 24 cases of ganglioneuroblastoma, and 65 cases of neuroblastoma. Stratified sampling was used to randomly allocate the cases into the training and validation sets in a ratio of 3:1. The maximum relevance-minimum redundancy algorithm was used to identify the top 10 of two clinical features and 851 radiomic features in portal venous-phase contrast-enhanced computed tomography images. Least absolute shrinkage and selection operator regression was used to classify tumors in two binary steps: first as ganglioneuroma compared to the other two types, then as ganglioneuroblastoma compared to neuroblastoma. RESULTS: Based on 10 clinical-radiomic features, the classifier identified ganglioneuroma compared to the other two tumor types in the validation dataset with sensitivity of 100.0%, specificity of 81.8%, and an area under the receiver operating characteristic curve (AUC) of 0.875. The classifier identified ganglioneuroblastoma versus neuroblastoma with a sensitivity of 83.3%, a specificity of 87.5%, and an AUC of 0.854. The overall accuracy of the classifier across all three types of tumors was 80.8%. CONCLUSION: Radiomic features can help predict the pathological type of neuroblastic tumors in children.

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.

Paediatric metastatic ganglioneuroblastoma on 68Ga-DOTA NOC PET-CT.

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We report a case of a 3-year-old boy who presented with a right paravertebral soft tissue mass. Biopsy showed ganglioneuroblastoma. The patient was referred for 68Ga-DOTA NOC for staging. 68Ga-DOTA NOC PET/CT images showed somatostatin-avid large right paravertebral soft tissue mass representing the primary lesion, along with increased radiotracer localization at multiple metastatic lytic bone lesions in the axial and appendicular skeleton. 68Ga-DOTA NOC PET-CT is helpful in the evaluation of the disease extent of neuroendocrine tumours including ganglioneuroblastoma.

Ganglioneuroblastoma Presenting as Obstructive Sleep Apnea in a 5-Year-Old Boy.

The authors present an interesting case of ganglioneuroblastoma, a tumor of the sympathetic chain, presenting as severe obstructive sleep apnea in a healthy 5-year-old boy. The patient's initial polysomnogram demonstrated an apnea-hypopnea index (AHI) of 86 events/hour. He underwent an adenotonsillectomy at an outside hospital and his repeat AHI was still 62. The patient was nonobese and nonsyndromic appearing, which made his incredibly high AHI perplexing. He underwent sleep endoscopy and direct laryngoscopy for further evaluation, which demonstrated a large mass in the left posterior pharynx. He then underwent surgical excision with a resolution of his obstructive sleep apnea.

Clinical and surgical outcome differences on the basis of pathology category in cervical neuroblastic tumors.

BACKGROUND: Cervical neuroblastic tumors (NTs) are rare but less aggressive cancer with an above-average survival rate. Little has been published regarding the management and surgical outcomes of patients with cervical NTs based on pathology category. This study compared and identified the preoperative characteristics of cervical NTs in different pathology categories and evaluated the outcomes of patients undergoing surgical resection. MATERIALS AND METHODS: Upon the institutional review board's approval, a retrospective chart review was performed at Beijing Children's Hospital from April 2013 to August 2020. Demographics of patients, imaging data, lab test results, operation details and outcomes were recorded and analyzed. RESULTS: Of 32 cervical NTs, 24(80%) were classified as neuroblastoma (NB) /ganglioneuroblastoma-nodular (GNBn) and 8(20%) as ganglioneuroblastoma-intermixed (GNBi)/ ganglioneuroma (GN). Patients with GNBi/GN were older than those with NB/GNBn (44.5 months (IQR 16-81) vs 9 months (IQR 1-47); P = 0.001). GNBi/GN patients presented more frequently with stage 1 disease compared with NB/GNBn patients (100% vs. 29.2%, P = 0.001), less frequently with tumor-related symptoms (0% vs. 70.8%, P = 0.001), artery encased tumor (0% vs. 41.7%, P = 0.035), and surgical complications (25% vs. 70.8%, P = 0.038). GNBi/GN patients were also less likely to show elevated neuron specific enolase (NSE) (12.5% vs. 79.2%, P = 0.002). CONCLUSIONS: Cervical NB/GNBn and GNBi/GN patients had distinct characteristic clinical presentations and surgical outcomes. For children with features suggestive of benign disease (older age, asymptomatic, normal serum tumor markers) and no artery image-defined risk factors (IDRFs), upfront resection can be considered.

Primary cervical ganglioneuroblastoma, nodular subtype.

Primary cervical ganglioneuroblastoma is rare and reports of its subtypes are limited. This case series describes two pediatric patients with the nodular subtype of primary cervical ganglioneuroblastoma with lymphatic spread. Clinical course, diagnosis, and management of this rare tumor are discussed with emphasis on the importance of including neuroblastic tumors in the differential diagnosis of pediatric neck masses. We also report the use of nerve monitoring of the recurrent laryngeal nerve as a surrogate for the vagus nerve during a pediatric neck dissection.

[Computed tomography-based radiomics for differential of retroperitoneal neuroblastoma and ganglioneuroblastoma in children].

OBJECTIVE: To explore the value of CT-based radiomics in differential diagnosis of retroperitoneal neuroblastoma (NB) and ganglioneuroblastoma (GNB) in children. METHODS: A total of 172 children with NB and 48 children with GNB were assigned into the training set and testing set at the ratio of 7∶3 using a random stratified sampling method. Radiomics features were extracted and selected from non-enhanced and post-enhanced CT images. Based on the subset of optimal features, a multivariate regression model was used to establish the radiomics models for each phase and the combined radiomics models. The ROC curves of the models were drawn, and the evaluation indexes such as AUC, accuracy, sensitivity and specificity of these models were calculated and compared. RESULTS: A total of 1218 radiomics features were extracted from the CT images acquired in non-enhanced (NP), arterial (AP) and venous phases (VP), from which 4 features from the NP model, 3 features from the AP model, 2 features from the VP model and 5 features from the combined model were selected. The AUC of the NP model in the training set and testing set was 0.840 (95% CI: 0.778-0.902) and 0.804 (95% CI: 0.699-0.899), respectively, as compared with 0.819 (95%CI: 0.759-0.877) and 0.815 (95%CI: 0.697-0.915) for the AP model, 0.730 (95%CI: 0.649-0.803) and 0.751 (95%CI: 0.619-0.869) for the VP model, and 0.861 (95%CI: 0.809-0.910) and 0.827 (95%CI: 0.726-0.915) for the combined model. CONCLUSION: Radiomics signature based on non-enhanced and post-enhanced CT images can be helpful for distinguishing retroperitoneal NB and GNB in children. Compared with the first-order histogram features, textural features can better reflect the difference of the lesions. NP, AP and VP models have similar classification efficacy in differentiating retroperitoneal NB and GNB. The efficacy of the combined model is similar to that of the NP and AP models, but superior to that of the VP model.

Olfactory ganglioneuroblastoma in a dog: case report and literature review.

A 7-y-old, intact male Alaskan Malamute was presented with a 3-mo history of stertor and epistaxis. Computed tomography of the skull revealed generalized loss of gas throughout both nasal passages with replacement by a soft tissue mass that traversed the cribriform plate. Histopathology revealed neoplastic neuroblast cells arranged in anastomosing cords, as well as separately located aggregates of ganglion cells. Both neoplastic cell populations demonstrated immunoreactivity to MAP-2, TuJ-1, and synaptophysin. Neuroblastic cells additionally exhibited punctate immunoreactivity to MCK and CK8/18. We document here both the positive neural immunohistochemical markers for this neoplasm, as well as propose possible histomorphologic variants.

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.

Harlequin syndrome associated with ganglioneuroblastoma-induced Horner syndrome.

A 1-year-old boy presented with a 4-month history of hypertension, ptosis of the right upper eyelid, left hemifacial sweating, and flushing. He was diagnosed with Harlequin syndrome associated with Horner syndrome. Computed tomography revealed a mass lesion in the right superior mediastinum. Therefore, the patient underwent total tumor resection. Histological examination demonstrated ganglioneuroblastoma. The MYCN oncogene was not amplified, and the mitosis-karyorrhexis index was low. Accordingly, radiation and chemotherapy were not performed. No recurrence was observed within 8 months after surgery, and the patient's blood pressure was normalized. However, the ptosis, hemifacial sweating, and flushing persisted.

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.

Suprasellar central nervous system ganglioneuroblastoma: a case in a 9-year-old child and review of the literature.

PURPOSE: Intracranial ganglioneuroblastomas are incredibly rare neuroectodermal tumors with only 8 described cases total, 5 of those having imaging findings METHODS: Here we present a 9-year-old female patient with 4 months progressive headaches, personality changes, and vomiting. We also present a review of the current literature of intracranial ganglioneuroblastomas. RESULTS: Imaging demonstrated a partially calcified suprasellar mass measuring 4.6 × 6.3 × 5 cm composed of both solid and cystic components, diagnosed to be a ganglioneuroblastoma, with mass effect on the lateral and 3rd ventricles, with a midline shift of right to left of 6-7 mm. She was treated with subtotal surgical resection, an intensive chemotherapeutic regimen, and radiation and has no residual disease on imaging 1 year and 4 months status post-surgery. CONCLUSION: To our knowledge, this is the first case of a ganglioneuroblastoma to mimic a craniopharyngioma based upon imaging findings and suprasellar location. As these cases are extremely rare, an optimal therapeutic regimen has not been defined. However, a combination of surgical resection, chemotherapy, and radiation therapy can be effective, as shown here with successful treatment and no evidence of residual disease.

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.