Pediatric oncological treatments significantly improved in the last decades with a significant positive impact on survival rates. Despite these achievements, cancer therapy is affected by side effects which may represent a diagnostic challenge and influence the overall management of children with tumors. Diagnostic imaging plays a crucial role in diagnosing adverse events, distinguishing them also from potential mimickers like infections or recurrences. Radiologists and nuclear medicine physicians are expected to have a deep knowledge of the common therapeutic schemes, their potential side effects, and features at imaging. Therefore, the aim of this review is to provide a comprehensive overview of the role of imaging, including hybrid techniques, in correctly identifying and characterizing the side effects of cancer treatment in children, including a brief overview of the main therapeutic options in pediatric oncology.

Five-year survival rates after childhood cancer have improved in recent decades: despite these promising survival rates, survivorship is associated with a lifelong increased risk of morbidity and mortality due to late effects of cancer and its treatments. Numerous studies have elucidated the long-term health consequences, and endocrine disorders are identified as among the most prevalent ones, impacting over 40

The study investigates how sex and age influence treatment response in paediatric, adolescent and young adult (AYA) classical Hodgkin lymphoma (cHL), integrating clinical data, immune-gene profiling and metabolic imaging from the European Network for Paediatric Hodgkin Lymphoma (EuroNet-PHL-C2 trial). cHL patients treated in Italian Association of Pediatric Hematology & Oncology Research (AIEOP) centres (2018-2020) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) at baseline, after two chemotherapy cycles early response assessment (ERA) and post-chemotherapy (late response assessment, LRA). Responses were classified as early complete metabolic response (CMR) or as adequate response (AR), inadequate (IR) or progressive disease at LRA. Tumour samples were profiled for 730 immune-related genes, and clinical and quantitative positron emission tomography parameters were integrated to assess sex- and age-related patterns. Sixty-eight cases passed quality control. Early CMR occurred in 51.5% at ERA; 29.4% showed (AR) at LRA. Older age (≥13 years), especially in males, was associated with higher IR risk. runt-related transcription factor 3 (RUNX3) expression characterized CMR; a five-gene panel (Bone Marrow Stromal Cell Antigen-1/CD157 [BST1]; C-X-C Motif Chemokine Receptor 6 [CXCR6]; Inducible T-cell Co-stimulator/CD278 [ICOS], Ubiquitin Specific Peptidase 9 Y-Linked [USP9Y], and Single Ig IL-1-Related Receptor/IL-1R8 [SIGIRR]) predicted IR and reflected sex-related immune differences. USP9Y expression correlated with baseline tumour volume (total metabolic tumour volume, TMTV1). Combining TMTV1 with RUNX3 improved CMR discrimination, while TMTV1 with the five-gene panel increased sensitivity but reduced accuracy at LRA. Sex and age influence immune response in AYA cHL. RUNX3 and the five-gene panel show promise as biomarkers of early and late response.

Pediatric-type follicular lymphoma (PTFL) is a rare, indolent B-cell neoplasm accounting for <2% of all pediatric non-Hodgkin lymphomas. Recently recognized as a distinct entity, PTFL predominantly affects young males and typically presents as localized lymphadenopathy in the head and neck region. Histologically, PTFL shows nodal effacement by large, irregular follicles composed of intermediate-sized blastoid cells with germinal center phenotype. On a genetic level, PTFL lacks BCL2 rearrangements and shows recurrent mutations of MAP2K1 and TNFRSF14 genes. The disease has an excellent prognosis, with 5-year overall survival over 95% and extremely low progression rates. The management is usually conservative after complete surgical excision. In this review, we highlight the unique clinical-pathological and biological features of PTFL, with a focus on its differential diagnosis and on potential therapeutic approaches.

To analyze risk factors for adverse outcomes in a nationally representative sample of pediatric cancer patients admitted to the PICU. An observational study composed of a 2-year retrospective phase and a 2-year prospective phase was conducted before and during PICU admission in Italian PICUs. We included 518 patients, median age 7.2 years (IQR 2.5–12.6). Main diagnosis: solid tumors (51

We analyzed 193 Fanconi anemia patients from the Italian Registry, focusing on hematological outcome, cancer risk, and mortality, both in transplanted (n = 130, 67.4% of the cohort) and non-transplanted (n = 63, 36.6% of the cohort) patients. After a median follow-up of 7 years, almost all patients developed cytopenia that was more frequent in patients receiving hematopoietic stem cell transplantation (HSCT). The cumulative overall survival from birth was 91.0% at age 10 years, 71.6% at age 20, and 47.4% at age 30 years; the median survival age was 29.1 years. When stratifying patients by indication for transplantation (moderate vs. severe cytopenia vs. persistent poor prognosis cytogenetic alterations/acute myeloid leukemia), we found a 5-year cumulative mortality higher, though not significantly (p = 0.281) in the last group. Cancers were the second most common cause of death in the whole cohort after infections. Head and neck squamous cell carcinoma was the most frequent cancer, followed by hematologic neoplasms. The cumulative incidence of solid/hematological malignancy remarkably increased after 20 years of age and was 51.7% at age 40 years. The risk of malignancies was greater in subjects who received HSCT (sub-distribution azard ratio 2.9, 95% CI: 1.1-7.5, p = 0.024). We also identified a small group of patients with stable or even improved cytopenia over time without transplant, thus confirming that bone marrow failure is not automatic in all patients and heightening the importance of tight monitoring to surveil on the worsening of hematopoietic function and cancer occurrence. Overall, this study provides important findings that may help to make robust clinical decisions.

Introduction: The most common pediatric types of mature B-cell non-Hodgkin lymphomas (B-NHLs)are: Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), accounting approximately for 7% of pediatric cancers, and mature B-cell acute lymphoblastic leukemia (mB-ALL). An increased EFS and OS has been observed in patients with mature B-NHLs/ mB-ALL receiving rituximab in addition to chemotherapy, as published in the pediatric international phase III randomized trial with stage III-IV B-NHLs (Minard-Colin V, N Engl J Med. 2020). Despite the excellent cure rate at diagnosis, prognosis remains dismal in case of relapse/resistant (R/R) disease. Standard-of-care reinduction strategy is yet to be identified, the most common pediatric regimens including ifosfamide/carboplatin/etoposide (ICE) and cytarabine/etoposide (CYVE) + rituximab. Several novel agents with activity against B-NHL are in development, including monoclonal and bispecific CD20-CD3 antibodies. Although the mechanism of resistance is unknown, the loss of CD20 expression in the R/R population could have a key role in the subsequent response. The aim of our retrospective study is the evaluation of CD20-expression by immunohistochemistry and/or flow cytometry in these neoplasms. Methods: We retrospectively collected data from children and young adults with R/R B-NHLs/mB-LLA and biopsy-proven CD20 status, treated in Italian Centers in the past 10 years (August 2014- August 2024). Patients, identified through individual sites querying local databases, were 20 years-old or less at diagnosis and 22 or less at relapse. Biopsy/cytological evaluation was performed at disease progression or whenever possible for confirmation of disease and CD20-expression evaluation. Results: Tumor cells from 25 pediatric patients/young adults with R/R LNHs and mB-ALL (12 Italian sites) were resampled at the time of the relapse diagnosis and CD20-protein expression was analyzed by flow cytometry and/or immunohistochemistry. Median age was 11,4 years (range, 4.1-19.3) at diagnosis (1 patient >18 years-old) and 12,3 at relapse (range,5.8- 21.3) (2 patients>18 years-old); 28% of patients were females. Twenty-one patients had relapsed or progressed following rituximab therapy, while 3 had not received the immunotherapy in combination during first-line treatment (1 not known). Burkitt Lymphoma was the most common diagnosis (10 patients), followed by DLBCL (6), mB-LLA (4), PMBCL (3); 1 patient had a B-mature lymphoma with mixed Burkitt/DLCBL features (1 patients not specified). Ten/25 patients (40%) showed the loss of CD20 expression by either immunohistochemisty and/or flow cytometry compared with diagnostic biopsies (all CD20 positive), biopsy being performed mostly at the first relapse (16 patients), followed by 2nd relapse (5), 5th relapse (2) and 6th relapse (1), 1 being unknown.Twenty-two patients received rituximab in first-line at the dose of 375 mg/m2; median number of infusions was 6 (range 0, 7). Relapse was diagnosed at less than 3 months for 17/24 patients, median time from last treatment being 3 months (range 0.2-66). Of the 10 CD20-negative patients, 7 died of progressive disease, 2 had a partial response (on treatment at the time of this writing :1 Burkitt lymphoma and 1 DLCBL) the remaining patient being alive and disease-free (after having experienced Hodgkin lymphoma as second cancer). In the 16 CD-20 positive patients, 6 patients died, 9 are alive (6 in complete remission, 2 partial response and 1 stable disease), 1 patient unknown. Seven patients were given hematopoietic stem cell transplantation (5 allogeneic, 2 autologous), 2 of which with a CD20 negative relapse. Three patients, all of them having been allotransplanted, are alive and disease free. Conclusion: Our retrospective data suggests that the loss of CD20 expression at relapse occurred in 40% of patients (few reports published in the literature in the adult population ranging from 14% to 60% (Kennedy Br, BJM2002; Hiraga J, Blood 2009)), CD20-loss is characterized by a more aggressive disease and worse outcome. Given the potential benefit of treatment with CD20 monoclonal or CD3-CD20 bispecific therapies, our observation suggest that the histological re-evaluation should be performed, whenever possible, to identify the ideal target-therapy.

AIMS:Bcl2-positive germinal centres (GCs) have never been documented in reactive lymphoid hyperplasia (RLH). Here we describe such phenomenon in paediatric chronic tonsillitis (PCT), addressing the differential diagnosis with paediatric lymphomas. METHODS AND RESULTS:Six PCT cases with Bcl2-positive GCs were retrieved from a retrospective series of 166 tonsillectomies from children and adolescents. Clinical-pathological data were collected, also considering the status of IG rearrangements and BCL2 translocations. PCT with Bcl2-positive GCs mostly occurred in males (5/6 cases; median age: 5 years). Histologically, tonsil architecture was preserved and Bcl2 positivity was documented in a minority of GCs. Bcl2-positive GCs expressed CD10 and Bcl6 and had a high proliferation index. All cases had polyclonal IG rearrangements without evidence of monotypic kappa and lambda chains by RNAscope. BCL2 translocations were lacking in all the cases. CONCLUSION:Bcl2-positive GCs in PCT are a rare and benign phenomenon, expanding the spectrum of lymphoma-mimicking paediatric RLH.

Pediatric oncohematological patients frequently require PICU admission during their clinical history. The O-PEWS is a specific score developed to predict the need for PICU admission of oncohematological children. This study aimed at i) describing the trend of the O-PEWS in a cohort of patients hospitalized in the Pediatric Oncohematology ward and transferred to the PICU of Padua University Hospital, measured at different time-points in the 24 hours before PICU admission and to evaluate its association with mortality and presence of organ failure; ii) investigating the association between the recorded O-PEWS, and PIM3, number of organ failure and the need for ventilation, dialysis and inotropes.This retrospective single-center study enrolled oncohematological children admitted to the PICU between 2017 and 2021. The O-PEWS, ranging between 0 and 15, was calculated on the available medical records and the TIPNet-Network database at 24 (T-24), 12 (T-12), 6 (T-6) and 0 (T0) hours before PICU admission.RESULTS: 101 PICU admissions, related to 80 children, were registered. During the 24 hours prior to PICU admission, the O-PEWS progressively increased in all the patients. At T-24 the median O-PEWS was 3 (IQR 1-5), increasing to a median value of 6 (IQR 4-8) at T0. The O-PEWS was positively associated with mortality, organ failure and the need for ventilation at all the analyzed time-points and with the need for dialysis at T-6.The O-PEWS appears as a useful tool for predicting early clinical deterioration in oncohematological patients and for anticipating the initiation of life-support treatments.