Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[¹²³I]iodobenzylguanidine ([¹²³I]mIBG) whole-body scintigraphy, usually combined with single-photon emission computed tomography with computed tomography (SPECT-CT). Nevertheless, 10% of neuroblastomas are mIBG non-avid and [¹²³I]mIBG imaging has relatively low spatial resolution, resulting in limited sensitivity for smaller lesions. More accurate methods to assess full disease extent are needed in order to optimize treatment strategies. Advances in nuclear medicine have led to the introduction of radiotracers compatible for positron emission tomography (PET) imaging in neuroblastoma, such as [¹²⁴I]mIBG, [¹⁸F]mFBG, [¹⁸F]FDG, [⁶⁸Ga]Ga-DOTA peptides, [¹⁸F]F-DOPA, and [¹¹C]mHED. PET has multiple advantages over SPECT, including a superior resolution and whole-body tomographic range. This article reviews the use, characteristics, diagnostic accuracy, advantages, and limitations of current and new tracers for nuclear medicine imaging in neuroblastoma.

Background: Malignant peripheral nerve sheath tumors (MPNST) are rare tumors of childhood. The role of standard chemotherapy in unresectable MPNST is still unclear. We report the outcome and prognostic factors in the EpSSG risk‐adapted prospective study for localized pediatric MPNST.Methods: Patients were stratified into four treatment groups defined by surgical resection, tumor size, and tumor grade (G): (a) surgery‐only group—resected tumors G1; (b) adjuvant radiotherapy group—R0/R1, G2 tumors; (c) adjuvant chemotherapy group—R0/R1, G3 tumors; and (d) neoadjuvant chemotherapy group—R2 resected tumors and/or nodal involvement. Chemotherapy consisted of four courses of ifosfamide‐doxorubicin and two courses of ifosfamide concomitant with radiotherapy (50.4‐54 Gy).Results: Overall, the study included 51 patients. The 5‐year event‐free survival (EFS) and overall survival (OS) were 52.9% (95% confidence interval, 38.1‐65.8) and 62.1% (46.7‐74.3), respectively. The 5‐year EFS was 92% (56.6‐98.9) for treatment group 1 (N = 13), 33% (0.9‐77.4) for treatment group 2 (N = 4), 29% (4.1‐61.2) for treatment group 3 (N = 7), and 42% (23.1‐60.1) for treatment group 4 (N = 27). Response rate to chemotherapy (partial response + complete response) in patients with measurable disease was 46%. The presence of neurofibromatosis type 1 (NF1; 51% of patients) was an independent poor prognostic factor for OS and EFS.Conclusion: The outcome for patients with resectable MPNST was excellent. Standard ifosfamide‐doxorubicin for unresectable MPNST rendered the best reported outcome. Children with NF1 disease seem to have worse prognosis.

Rhabdomyosarcomas (RMS) are mesenchyme‐derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high‐risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4–8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.

EWSR1 belongs to the FET family of RNA-binding proteins including also Fused in Sarcoma (FUS), and TATA-box binding protein Associated Factor 15 (TAF15). As consequence of the multifunctional role of EWSR1 leading to a high frequency of transcription of the chromosomal region where the gene is located, EWSR1 is exposed to aberrations such as rearrangements. Consecutive binding to other genes leads to chimeric proteins inducing oncogenesis. The other TET family members are homologous. With the advent of widely used modern molecular techniques during the last decades, it has become obvious that EWSR1 is involved in the development of diverse benign and malignant tumors with mesenchymal, neuroectodermal, and epithelial/myoepithelial features. As oncogenic transformation mediated by EWSR1-fusion proteins leads to such diverse tumor types, there must be a selection on the multipotent stem cell level. In this review, we will focus on the wide variety of soft tissue and bone entities, including benign and malignant lesions, harboring EWSR1 rearrangement. Fusion gene analysis is the diagnostic gold standard in most of these tumors. We present clinicopathologic, immunohistochemical, and molecular features and discuss differential diagnoses.