Neuroblastic Tumors Research Articles

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.

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.

Cervical ganglioneuroma: a case report

Cervical ganglioneuroma (CGN) is a rare benign tumour that originates from the neurogenic soft tissue of the cervical sympathetic chain. It is part of the neuroblastic tumours that arise from the neural crest cells of the central or peripheral nervous system. The clinical presentation can range from a palpable mass in the neck, dysphagia, dysphonia, or features of Horner’s syndrome. We present a case of a 65-year-old lady that was seen in the ENT outpatient clinic with complaints of left-sided neck swelling, dysphagia, and dysphonia. Complete surgical excision of the mass revealed the histological diagnosis of CGN. Treatment is considered complete when the entire specimen is excised.

The Pitfall of Ganglioneuroblastoma-Nodular Diagnosis: Clinical and Imaging Considerations over a Rare Bifocal Sporadic Case.

Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed. Herein, we describe a case of multifocal NT (thoracic and abdominal localization) occurring in a 4-year-old male. Different histological subtypes, namely GNBI and GNBN, were revealed in the two lesions. We focus on the difficulties of proper diagnosis and risk stratification, underlining the usefulness of several diagnostic tools for appropriate management and therapeutic choices.

Galanin family peptides: Molecular structure, expression and roles in the neuroendocrine axis and in the spinal cord.

Galanin is a neurohormone as well as a neurotransmitter and plays versatile physiological roles for the neuroendocrine axis, such as regulating food intake, insulin level and somatostatin release. It is expressed in the central nervous system, including hypothalamus, pituitary, and the spinal cord, and colocalises with other neuronal peptides within neurons. Structural analyses reveal that the human galanin precursor is 104 amino acid (aa) residues in length, consisting of a mature galanin peptide (aa 33-62), and galanin message-associated peptide (GMAP; aa 63-104) at the C-terminus. GMAP appears to exhibit distinctive biological effects on anti-fungal activity and the spinal flexor reflex. Galanin-like peptide (GALP) has a similar structure to galanin and acts as a hypothalamic neuropeptide to mediate metabolism and reproduction, food intake, and body weight. Alarin, a differentially spliced variant of GALP, is specifically involved in vasoactive effect in the skin and ganglionic differentiation in neuroblastic tumors. Dysregulation of galanin, GALP and alarin has been implicated in various neuroendocrine conditions such as nociception, Alzheimer's disease, seizures, eating disorders, alcoholism, diabetes, and spinal cord conditions. Further delineation of the common and distinctive effects and mechanisms of various types of galanin family proteins could facilitate the design of therapeutic approaches for neuroendocrine diseases and spinal cord injury.

Neuroblastic tumors and neurofibromatosis type 1: A retrospective multicenter study in Italy and systematic review of the literature.

Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest-derived disorders. To explore the occurrence of NBTs within NF1 and to report on its natural history, therapeutic strategies, and outcomes in an Italian cohort of children with NF1 and in the literature. Study (a): a retrospective analysis of questionnaire-based data [years 1979-2017] derived from the databases of the Italian Registry for Neuroblastoma (RINB) of the Italian Society of Pediatric Onco-Haematology (AIEOP); and Study (b): a systematic review search on NF1/NB co-occurrence. Study (a) identified eight children with NBTs, 0.2% of patients registered in the RINB, fulfilling the diagnostic criteria for NF1. The primary site of NBTs was abdominal in six patients. The NBTs were neuroblastoma (NB) in five patients, ganglioneuroblastoma (GNB) in one, patient, and ganglioneuroma (GN) in two. Metastatic diffusion occurred in three out of eight children. MYCN gene testing, performed in the tumors of five patients, resulted not-amplified. The major features of NF1 included the following: NF1 family history in four patients, café-au-lait spots in all, freckling in six, Lisch nodules in three, and neurofibromas in three. With regard to the outcome, four children survived three of these for the progression of NB and one for a second tumor. Study (b) identified 12 patients with NF1/NB from the years 1966-2017, and the median age at diagnosis was 27 months (range = 0-168 months). The primary site of NB was thoracic. The prevalent histotype was NB in nine patients, GNB in two, and GN in one. Eight/nine NBs were metastatic. The MYCN gene was amplified in the only studied case. The NF1 features included NF1 family history in seven patients; the major NF1 features were café-au-lait spots in nine patients, freckling in one, Lisch nodules in none, and neurofibromas in six. The outcome was good for only two children, while eight children died of neuroblastoma, at a median age of 49.5 months (range = 2.4-174 months), with a median survival time of 21.75 months after diagnosis. To our knowledge, this represents the first systematic study on the occurrence of NBTs in NF1. This confirms that NBs are rare per se in the setting of NF1 (0.2% of all NBs) and even if compared to the overall frequency of malignancies in NF1 (i.e., 14.7%). The male:female ratio in study (a) (0.6) was different from what was recorded in study (b) (1.5) and in line with the overall increased frequency of malignancies in females with NF1. The median ages at diagnosis of NB in either study (a) or (b) were concordant with what occurred in the NB population. In study (a) versus study (b), the frequency of metastatic diffusion was lower, likely indicating less awareness on work-ups for malignancies in old NF1 series in the literature. The outcome was much better in study (a) than in study (b), indicating that multidisciplinary treatment for NB is highly recommended.

PMON104 Sellar Gangliocytoma-Pituitary Neuroendocrine Tumor (PitNET) Presenting As Acromegaly

Abstract Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNET) arising from somatotrophs is the most common cause of acromegaly. It may rarely develop in the setting of a growth hormone-secreting PitNET associated with a neuronal tumor composed of neoplastic ganglion cells, the so-called mixed gangliocytoma somatotroph PitNET. We present a case of acromegaly which proved to be due to a mixed gangliocytoma somatotroph PitNET on pathology.A 58-year-old, healthy woman presented to the ER with a 3-day history of left-sided vision loss and worsening headache. MRI revealed 4.5×4.2×3.8 cm heterogeneously enhancing bilobed mass consistent with a pituitary PitNET with suprasellar extension causing compression of the optic chiasm, invasion into the left cavernous sinus and partial encasement of the left internal carotid artery. She had coarse facial features, wide feet, multiple skin tags, and a history of multiple colonic polyps. Biochemical work up revealed an IGF-I of 664 ng/ml (50-317), AM cortisol 19.7 mg/dl, ACTH 30 pg/ml, prolactin 15.5 ng/ml, FSH 35.6 mIU/ml, LH 11.3 mIU/ml, and FT4 0.7 ng/dl (0.70-1.48). She underwent endoscopic transsphenoidal resection of the tumor. Histopathology demonstrated mature ganglion cells with neuropil-like areas, intermixed with small cell components. The neuronal population was immunopositive for NeuN (Neuronal nuclei antibody), synaptophysin, and NF (Neurofilament). PitNET cells were positive for GH, prolactin, Pit- 1 transcription factor and the somatostatin 5 receptor, histological features consistent with mixed gangliocytoma and sparsely granulated somatotroph pitNET. Some ganglion cells also showed weak immunostaining with Pit-1. A 3-month follow-up MRI showed a residual 3 cm lesion. IGF-I improved but was still elevated at 456 ng/ml associated with a GH 2.9 ng/ml. Medical treatment with pasireotide was recommended, but the patient temporarily declined further treatment to explore other options with her Naturopath.Gangliocytomas are a rare, benign, slow-growing, differentiated form of neuroblastic tumors of sympathetic nerve fibers, largely extracranial and rarely present in the sellar region, most frequently in association with a PitNET, forming the so-called mixed gangliocytoma PitNET. Definitive diagnosis is established by histological and immunohistochemical studies. Though PitNET components of mixed gangliocytoma PitNET are known to frequently secrete an excess hormone, the ganglionic components also show immunoreactivity for hypothalamic releasing hormones along with other neuroendocrine markers. The histological origin of these mixed tumors is controversial, but the small population of ganglionic cells that express the acidophilic lineage transcription factor, Pit-1, favors the theory of transdedifferentiation of neuroendocrine cells into neuronal elements. Treatment of mixed gangliocytoma- PitNET is similar to other PitNETs and the presence of neural components does not modify aggressiveness or risk of recurrence after surgical resection, as gangliocytomas have a low proliferative index. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Synthesis and evaluation of small molecule inhibitors of LSD1 for use against MYCN-expressing neuroblastoma

The epigenetic regulator lysine specific demethylase 1 (LSD1), a MYCN cofactor, cooperatively silences MYCN suppressor genes. Furthermore, LSD1 has been correlated with adverse effects in neuroblastic tumors by propagating an undifferentiated, malignant phenotype. We observed that high LSD1 mRNA expression in MYCN-expressing neuroblastoma (NB) correlated with poor prognosis, implicating LSD1 as an oncogenic accomplice in high-grade NB. Thus, LSD1 inhibition is a potential strategy for targeting treatment-resistant MYCN-expressing NB. Tranylcypromine-based covalent LSD1 inhibitors have demonstrated anti-tumor activity but are associated with undesirable off-target effects, such that only 2 non-covalent LSD1 inhibitors are in clinical trials. We now report 3 novel scaffolds for reversible LSD1 inhibition: 2-(arylsulfonamido)benzoic acid, N-(2-(1H-tetrazol-5-yl)phenyl)benzenesulfonamide and 2-(arylcarboxamido)benzoic acid analogues. The most active of these analogues, compound 48, exhibited potent and selective mixed reversible inhibition of LSD1 (IC50 = 0.58 μM) and significantly increased global H3K4me2 in NB cells. In addition, combination treatment with 48 and bortezomib in NB cells results in a synergistic effect.

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.

The Galaninergic System: A Target for Cancer Treatment.

Simple SummaryPeptidergic systems play an important role in cancer progression. The galaninergic system (the peptide galanin and its receptors: galanin 1, 2 and 3) is involved in tumorigenesis, the invasion and migration of tumor cells and angiogenesis and it has been correlated with tumor stage/subtypes, metastasis and recurrence rate in many types of cancer. Galanin exerts a dual action in tumor cells: a proliferative or an antiproliferative effect depending on the galanin receptor involved in these mechanisms. Galanin receptors could be used in certain tumors as therapeutic targets and diagnostic markers for treatment, prognosis and surgical outcome. This review shows the importance of the galaninergic system in the development of tumors and suggests future promising clinical antitumor applications using galanin agonists or antagonists.The aim of this review is to show the involvement of the galaninergic system in neuroendocrine (phaeochromocytomas, insulinomas, neuroblastic tumors, pituitary tumors, small-cell lung cancer) and non-neuroendocrine (gastric cancer, colorectal cancer, head and neck squamous cell carcinoma, glioma) tumors. The galaninergic system is involved in tumorigenesis, invasion/migration of tumor cells and angiogenesis, and this system has been correlated with tumor size/stage/subtypes, metastasis and recurrence rate. In the galaninergic system, epigenetic mechanisms have been related with carcinogenesis and recurrence rate. Galanin (GAL) exerts both proliferative and antiproliferative actions in tumor cells. GAL receptors (GALRs) mediate different signal transduction pathways and actions, depending on the particular G protein involved and the tumor cell type. In general, the activation of GAL1R promoted an antiproliferative effect, whereas the activation of GAL2R induced antiproliferative or proliferative actions. GALRs could be used in certain tumors as therapeutic targets and diagnostic markers for treatment, prognosis and surgical outcome. The current data show the importance of the galaninergic system in the development of certain tumors and suggest future potential clinical antitumor applications using GAL agonists or antagonists.

Free floating abdominal ganglioneuroblastoma in a 3 year old male

This is a case of a 3 year old male with a free floating neuroblastic tumor in the abdomen that was unattached to any organs. A focused comprehensive literature search was conducted, which yielded no results for a case with this presentation. This case involves a 3 year old male who presented to the emergency department after 3 days of vomiting (projectile, non-bloody, non bilious) after every meal. The patient complained of generalized abdominal pain that resolves after vomiting, and a mass was palpated in the left lower quadrant (LLQ), consistent with ultrasound findings that showed a 7 cm discrete mass medial to the spleen and superior to the left kidney. Surgical resection of ganglioneuroblastoma is typically curative and has low complication rates. During clinical follow up for this patient, patient had no subsequent symptoms suspicious of recurrence. Thus, we hypothesize that because his tumor was free-floating, this could possibly be a contributing factor for him to continue to stay disease free in the future. This is the first reported case of a free floating abdominal ganglioneuroblastoma. This unique feature can present special considerations surgically and have an impact on symptom presentation and prognosis.

Comparative Multicentric Evaluation of Inter-Observer Variability in Manual and Automatic Segmentation of Neuroblastic Tumors in Magnetic Resonance Images.

Simple SummaryTumor segmentation is a key step in oncologic imaging processing and is a time-consuming process usually performed manually by radiologists. To facilitate it, there is growing interest in applying deep-learning segmentation algorithms. Thus, we explore the variability between two observers performing manual segmentation and use the state-of-the-art deep learning architecture nnU-Net to develop a model to detect and segment neuroblastic tumors on MR images. We were able to show that the variability between nnU-Net and manual segmentation is similar to the inter-observer variability in manual segmentation. Furthermore, we compared the time needed to manually segment the tumors from scratch with the time required for the automatic model to segment the same cases, with posterior human validation with manual adjustment when needed.Tumor segmentation is one of the key steps in imaging processing. The goals of this study were to assess the inter-observer variability in manual segmentation of neuroblastic tumors and to analyze whether the state-of-the-art deep learning architecture nnU-Net can provide a robust solution to detect and segment tumors on MR images. A retrospective multicenter study of 132 patients with neuroblastic tumors was performed. Dice Similarity Coefficient (DSC) and Area Under the Receiver Operating Characteristic Curve (AUC ROC) were used to compare segmentation sets. Two more metrics were elaborated to understand the direction of the errors: the modified version of False Positive (FPRm) and False Negative (FNR) rates. Two radiologists manually segmented 46 tumors and a comparative study was performed. nnU-Net was trained-tuned with 106 cases divided into five balanced folds to perform cross-validation. The five resulting models were used as an ensemble solution to measure training (n = 106) and validation (n = 26) performance, independently. The time needed by the model to automatically segment 20 cases was compared to the time required for manual segmentation. The median DSC for manual segmentation sets was 0.969 (±0.032 IQR). The median DSC for the automatic tool was 0.965 (±0.018 IQR). The automatic segmentation model achieved a better performance regarding the FPRm. MR images segmentation variability is similar between radiologists and nnU-Net. Time leverage when using the automatic model with posterior visual validation and manual adjustment corresponds to 92.8%.

Concordance and diagnostic yield of stereotactic biopsies for posterior fossa: Technique and experience in a reference hospital.

Describe our stereotactic brain biopsy (SBB) technique for intra-axial lesions of the posterior fossa, evaluate its effectiveness and safety, and compare them with other series. Retrospective study in ten consecutive patients, whose variables were age, gender, location of the lesions, clinical, radiological, and histopathological diagnoses, complications, and mortality, for analysis using descriptive statistics and tests of concordance and diagnostic validity. Lesions were pontine in seven cases, and pontomedullary in three occasions, with histopathological diagnoses of four Grade II astrocytomas, two Grade IV astrocytomas, two infectious process, one neuroblastic tumor, and one cavernous malformation, whose frequency differs from the previous reports (χ2 = 0.07). The clinical-radiological concordance was poor (κ = 0.20). The validity of the clinical diagnosis had intermediate values (Sn = 66.7%, Sp = 75%), while radiological studies were more sensitive (Sn = 100%, Sp = 25%). A definitive diagnosis was obtained in all procedures, with no permanent morbidity or mortality because of the surgery. The SBB technique for posterior fossa implemented in our hospital shows high diagnostic yield, as well as absolute safety for the patient.

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.

Comparison of two Schwann Cell-Containing Orbital Tumors: Schwannoma and Ganglioneuroma.

Orbital tumors comprise a variety of diseases, although tumors of the peripheral nerves are rare. Of these, schwannoma is considered the most common entity, consisting histopathologically almost exclusively of Schwann cells. Another benign tumor containing Schwann cells is ganglioneuroma. Here, ganglion cells are histopathologically apparent in addition to the Schwann cell-containing stroma. Ganglioneuroma belongs to the group of neuroblastic tumors and can occur anywhere in the pathway of sympathetic ganglion cells. In this report, we present the disease courses as well as the findings of two patients with different orbital tumors. In both cases, the diagnosis was only confirmed by histopathological examination. The first patient had a schwannoma with cystic degeneration and the second patient had a ganglioneuroma, both tumor entities which occur only rarely in the orbit. Commonalities and differences are discussed.

A comparison between ultrasonography and single-phase computed tomography for preoperative assessment of solid abdominal tumors in children

ObjectiveThis study aimed to estimate the performance of single-phase-enhanced computed tomography and ultrasonography examinations in the preoperative evaluation of solid abdominal tumors and their relationship with relevant adjacent structures in children. MethodsThis retrospective study included 50 pediatric patients with malignant solid abdominal tumors treated with surgical resection between 2009-2017. Preoperative computed tomography and ultrasonography were compared to operative findings (gold standard) in the diagnosis of invasion or encasement of adjacent structures. Accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated. ResultsRenal (20.4%) and neuroblastic (19.4%) tumors were the most common. Complete surgical resection with negative margins was achieved in 44 (88%) patients. The comparison between single-phase-enhanced computed tomography and ultrasonography findings showed the following results: sensitivity = 90.3% vs 86.6%, specificity = 86.8% vs 94.6%, negative predictive value = 95.3% vs 94.4%, positive predictive value = 75.3% vs 86.9%, and accuracy = 87.9% vs 92.2%. The correlation (kappa index) between computed tomography and ultrasonography examinations was 0.72 (p < 0.001). In 14% (7/50) of the patients, the invasion of adjacent structures was diagnosed by ultrasonography but not by computed tomography (1 patient had 2 invaded structures). ConclusionUltrasonography can be considered a complementary method to single-phase-enhanced computed tomography in the preoperative evaluation of children with an abdominal tumor. The present study showed that ultrasonography and single-phase-enhanced computed tomography each possess a high accuracy in the preoperative planning of resection of solid abdominal tumors in children. Thus, it seems that the combination of both imaging methods would be enough for the evaluation of most abdominal tumors in the pediatric population.

Solid malignancies during the first year of life: A 20-year review at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

Background. Among paediatric tumours, two groups stand out: neonatal and infantile tumours, which respectively represent 2% and 10% of paediatric tumours. The distribution of tumours in these age groups is different from that in older children. Objectives. Descriptive analysis of a cohort of patients treated for a solid malignancy at Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa. Methods. A 20-year retrospective case series review of patients aged &lt;1 year at diagnosis was performed on data extracted from the RCWMCH oncology database. Results. Of 243 cases extracted from the database, 198 were solid tumours, of which 122 (61.1%) were included in the analysis; the 76 excluded were benign or of eye, bone or central nervous system origin and therefore did not meet the inclusion criteria. There were 38 renal malignancies (31.2%), 30 neuroblastomas (24.6%), 25 soft-tissue sarcomas (20.5%), 17 germ cell tumours/gonadal tumours (13.9%) and 12 liver tumours (9.8%). Of the patients, 119 (97.5%) had surgery, 91 (74.6%) had chemotherapy and 10 (8.2%) had radiotherapy. Tumour group 5-year survival was 78.5% for neuroblastic tumours, 79.0% for nephroblastomas, 81.5% for hepatoblastomas, 62.5% and 54.2% for rhabdomyosarcoma and non-rhabdomyosarcoma soft-tissue sarcomas, respectively, and 79.5% for malignant extracranial and extragonadal germ cell tumours. For the entire cohort, the mean follow-up was 46 months, with an estimated 5-year overall survival of 74.6%. Mortality was 21.5% and loss to follow-up 6.6%. Conclusion. The distribution of tumours differs slightly from the literature, with a predominance of renal tumours over neuroblastomas. The overall mortality rate of 21.5%, the surgical complication rate of 10.9% and the 5-year overall survival of 74.6% correspond with the literature, supporting the view that a paediatric hospital in a middle-income country can achieve results similar to those in higher-income countries when international protocols are applied by a dedicated multidisciplinary team.

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

Automated Tumor Count for Mitosis-Karyorrhexis Index Determination in Neuroblastoma Using Whole Slide Image and Qupath, an Image Analytic Software

Mitosis-karyorrhexis index (MKI) is important for risk stratification workup of neuroblastic tumors. MKI is calculated by estimating the denominator (5000 tumor cells). We hypothesized that whole slide image (WSI) with appropriate digital image analytical software could provide an objective aid to pathologist's MKI workup. With IRB approval, sixteen cases of neuroblastic tumors as convenient cases were used. H&E slides were scanned at 40X using an Aperio Scanscope AT2 scanner and stored in SVS format. Digital photos were also taken and stored in TIFF format. Qupath, an open source image analytical software, was used to annotate, define region of interest (ROI) and automatically count the cells within ROI. With selected parameters, Qupath was able to provide cell count using both WSI (.svs) and digital images (.TIFF). Comparison of automated count and eyeball manual count generated precision above .96, recall above .96, F1 scores above .98, with false positive rate ranging from .6 to 3.7%, and false negative rate from .6 to 3.8%. Compared to original pathological report, automated tumor cell count led to lower MKI in 3 of 16 cases (18.8%) and change of "unfavorable histology" to "favorable" in one case (1/16, 6.3%). Combination of WSI (or digital images) with Qupath is able to provide an automated, objective and consistent way for cell count to facilitate pathologist's MKI determination in neuroblastic tumors' workup and research.