More than 50% of children with stage 4 NB may survive. The high incidence of severe long-term sequelae underlines the importance of careful follow-up in order to detect and treat late effects early enough.

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Background Data on management of gray zone lymphoma (GZL) in children and adolescents are scarce. Procedure This retrospective study assessed clinical characteristics and outcome in six Austrian patients with GZL less than 18 years of age (male‐to‐female ratio: 1:1; median age: 15.8 years). Results Two patients each had a classical Hodgkin lymphoma (cHL)‐like and composite GZL subtype, and one patient each had a large B‐cell non‐Hodgkin lymphoma (LBCL)‐like and sequential GZL subtype. All had advanced disease with mediastinal and extranodal involvement. Five patients received an LBCL‐ and one patient a cHL‐directed polychemotherapy ± radiotherapy. Out of the former patients, three survived, including two who relapsed and underwent high‐dose chemotherapy with autologous stem cell rescue. The latter patient survived. Conclusions GZL remains a diagnostic and therapeutic challenge, necessitating the development of novel treatment concepts performed in a prospective setting.

Background The WHO Classification of Tumors of the Central Nervous System has undergone major restructuring. Molecularly defined diagnostic criteria were introduced in 2016 (revised 4th edition) and expanded in 2021 (5th edition) to incorporate further essential diagnostic molecular parameters. We investigated potential differences between specialists in perception of these molecularly defined subtypes for pediatric high-grade gliomas (pedHGG). Methods We designed a 22-question survey studying the impact of the revised 4th edition of the WHO classification on pedHGG. Data were collected and statistically analyzed to examine the spectrum of viewpoints and possible differences between neuro-oncologists and neuropathologists. Results 465 participants from 53 countries were included; 187 pediatric neuro-oncologists (40%), 160 neuropathologists (34%), and 118 additional experts (26%). Neuro-oncologists reported issues with the introduction of molecularly defined tumor types, as well as the abolishment or renaming of established tumor entities, while neuropathologists did not to the same extent. Both groups indicated less relevant or insufficient diagnostic definitions were available in 2016. Reported issues were classified and assessed in the 2021 WHO classification and a substantial improvement was perceived. However, issues of high clinical relevance remain to be addressed, including the definition of clinical phenotypes for diffuse intrinsic pontine glioma and gliomatosis cerebri. Conclusions Within the WHO classification of pediatric brain tumors, such as pedHGG, rapid changes in molecular characterization have been introduced. This study highlights the ongoing need for cross talk between pathologist and oncologist to advance the classification of pedHGG subtypes and ensure biological relevance and clinical impact.

Background Knowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce. Methods We analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n=36), SIOP-LGG 2004 (n=56) and the subsequent LGG-Interim registry (n=36). Results Spinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93±2% and 38±5%, respectively. Disseminated disease (n=16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n=24) or subtotal/partial resection (n=74), biopsy (n=16), or radiologic diagnosis only (n=3). Eleven patients were treated first with chemotherapy (n=9) or irradiation (n=2). Up to 20.8 years after diagnosis/initial intervention 73/128 patients experienced one (n=43) or up to six (n=30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required non-surgical treatment (chemotherapy, n=20; radiotherapy, n=10; multiple treatment lines, n=17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n=57) or repeated (n=16) resections, and in 35/47 patients after non-surgical treatment. Conclusions The majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.