Pediatric Tumors Research Articles

Paediatric Renal Tumors: A State-of-the-Art Review.

Pediatric renal tumors comprise a wide range of conditions, both malignant and benign, that affect children and require a multidisciplinary approach for optimal diagnosis and treatment. This review offers an in-depth analysis of the epidemiology, diagnosis, treatment options, outcomes, and survival of major pediatric renal tumors. Wilms tumor, or nephroblastoma, is the most common form of renal tumor in children, characterized by growth from primitive renal cells. Standard treatment involves a combination of surgery, chemotherapy and, in some cases, radiation therapy, with the aim of removing the tumor, preventing recurrence and maximizing the chances of long-term recovery. Less common pediatric renal tumors, such as renal clear cell sarcoma, renal cell carcinoma, mesoblastic nephroma, and malignant rhabdoid tumor, require similarly careful and individualized management. Therapeutic strategies, which depend on the characteristics of the tumor, the stage of the disease and the individual response to therapy, may include surgery, chemotherapy, radiotherapy and, in some cases, molecular targeted therapies, immunotherapies and genetic and epigenetic therapies. The management of pediatric kidney tumors requires the involvement of a multidisciplinary team of specialists to ensure accurate evaluation, optimal treatments and long-term follow-up. The aim is to maximize the prospects for recovery and improve the quality of life of patients and their families. Advances in innovative, personalized therapies represent an important opportunity to further improve clinical outcomes in these patients.

Untargeted Metabolomics and Liquid Biopsy Investigation of Circulating Biomarkers in Soft Tissue Sarcoma

Background: Soft tissue sarcomas (STSs) are rare, highly malignant mesenchymal tumours, comprising approximately 1% of all adult cancers and about 15% of paediatric solid tumours. STSs exhibit considerable genomic complexity with diverse subtypes, posing significant clinical challenges. Objectives: This study aims to characterise the molecular signature of primary STS through liquid biopsies and the untargeted metabolomic profiling of 75 patients, providing deep insights into cellular processes and potential therapeutic targets. Methods: This study analysed serum samples using nuclear magnetic resonance (NMR) spectroscopy for metabolomic profiling. Multivariate data analysis and machine learning classifiers were employed to identify biomarkers. Results: A panel of eleven significant deregulated metabolites were discovered in serum samples of patients with STS, with potential implications for cancer diagnosis and treatment. Conclusions: Choline decrease emerged as a marker for cancer progression, highlighting the potential of targeting its metabolism for therapeutic approaches in STS. The NMR analysis protocol proved effective for determining circulating biomarkers from liquid biopsies, making it suitable for rare disease research.

Retraction Note: Letter to the editor, "Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes".

Retraction Note: Letter to the editor, "Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes".

Image-Guided Biopsy for the Diagnosis and Molecular Profiling of Hepatoblastoma.

Studies on the use of image-guided percutaneous biopsy for hepatoblastoma (HB), and recommendations put forth by the pediatric hepatic international tumor trial (PHITT), are limited. It is unknown if sufficient tissue can be obtained for trial enrollment as well as molecular profiling, which will likely play a key role in informing future treatment strategies. Patients with HB who underwent percutaneous biopsy at initial diagnosis in interventional radiology (IR) over a 12-year period at a single center were included. Patient demographics, pretreatment extent of disease (PRETEXT) stage, tumor size, and procedure details were collected. Pathology reports and tumor genomic analysis, when performed, were assessed for specimen adequacy. Post-procedure records were assessed for hemoperitoneum. A total of 33 percutaneous biopsies were performed on 32 patients [17 female; median age 1.3 years (IQR: 0.7-2.5 years); median weight 10.5kg (IQR: 7.4-12.7kg)]. Most (n=27) had a single liver lesion, and most (n=18) were PRETEXT II. A total of 15 were positive for at least one annotation factor. Median longest tumor axis was 9.3cm (IQR: 5.0-13.5cm). A total of 16 patients had concurrent non-targeted liver biopsy, per PHITT recommendations. An 18-gauge instrument was most commonly used (n=24, 73%) with a median of 8 cores (IQR: 6-12) obtained. There were no instances of hemoperitoneum. Tissue was adequate for histologic diagnosis in 97% (n=32), with histologic subtyping obtained in 94% (30/32). When available (n=29), comparison with the subsequent surgical resection specimen showed subtype concordance in 15 (52%) patients and minor variations secondary to sampling or treatment effect in 14 patients. Molecular profiling was completed on 21/21 specimens (100%), with 19/21 (90%) showing potentially clinically significant variants, most commonly in CTNNB1 (16/21). In this single-center study, percutaneous biopsy resulted in no serious adverse events, a high rate of diagnosis, and successful subtyping and molecular characterization of HB.

Re-Irradiation for the Progressive Pediatric Diffuse Intrinsic Pontine Glioma: A Report on 109 Children From a Single Center.

Diffuse intrinsic pontine glioma (DIPG) is a challenging pediatric tumor that frequently progresses within the first year following local radiotherapy. However, several small studies have suggested that re-irradiation may improve quality of life and extend overall survival. This retrospective study included 109 children who experienced disease progression ≥3months after their initial radiotherapy, and subsequently received re-irradiation at a single institution. These patients were compared with a cohort of 60 children, meeting the same criteria, who were treated before adopting the re-irradiation policy and received only the best supportive care (BSC). Most of the re-irradiated children (94%) received first radiation dose as hypofractionation (39Gy/13 fractions). The re-irradiation group demonstrated significantly higher overall survival (OS) rates after the first progression, with a 6-month OS of 42% (95% CI: 34%-53%) compared to 16% (95% CI: 8.9%-32%) in the BSC group (p < 0.001). Re-irradiation reduced the hazard of death by more than half (HR = 0.45, p < 0.001). Clinical response (p < 0.001) and radiological response (p = 0.016) were significant predictors of improved survival. While the time from initial radiotherapy to progression (p = 0.059) and higher re-irradiation doses (p = 0.074) were associated with improved OS, these factors did not reach statistical significance but may represent potential prognostic indicators. Re-irradiation improved the OS in children with progression of DIPG and alleviated their signs and symptoms.

Cervical Lymph Node Invasion in Pediatric Salivary Gland Malignancies: Clinical Overview and Therapeutic Implications.

Pediatric salivary gland malignancies (SGM) present challenges in managing cervical nodes. We aimed to characterize lymph node invasion to inform decisions regarding the need of systematic wide lymph node dissection (WLND). International retrospective study, conducted across seven large French and American pediatric centers, including pediatric patients (0-18 years) diagnosed with SGM from 2000 to 2020. Among the 82 patients (median age 13 years), the parotid gland was frequently affected (60 cases). Histotypes comprised mucoepidermoid (mucoepidermoid carcinoma [MEC], 43 cases), acinic cells (acinic cells carcinoma [AcCC], 22 cases), adenoid cystic (adenoid cystic carcinoma [AdCC], 8 cases), (MASC, 6 cases), and adenocarcinoma (3 cases). Primary treatments were surgery (82 cases) and radiotherapy (20 cases; median dosage 64 gray). Cervical nodes therapy included WLND (≥2 levels, 29 cases), limited nodes resection (LNR; one level, 13 cases), and/or irradiation (4 cases; median 54 gray; range 52.0-63.0). At diagnosis, six patients had cervical node invasion (CNI) managed with LNR (four cases), WLND (two cases), and radiotherapy (three cases). After a median follow-up of 6 years (range 1-22), nine patients had tumor event: local (four cases), cervical relapse/progression (three cases) or combined (two cases). Of the nine with CNI, at diagnosis or relapse, four had MASC. Five-year event-free and overall survival (OS) rates were, respectively, 90.1% and 98.8%. CNI is rare in pediatric SGM but noted in 11% of cases, with higher incidence in MASC. Overall, outcome in SGM is good with a tailored locoregional multidisciplinary approach. Systematic lymph node dissection should be reconsidered. This international multi-institutional study analyzed the clinical presentation and the cervical pattern of relapse of 82 pediatric patients with newly diagnosed salivary gland malignancies. Overall, nodal invasion was rare at diagnosis and only noted in 7%. In addition, 6% developed nodal relapse during follow-up. Incidence of nodal spread was frequent in mammary analogue secretory carcinoma (MASC). The overall outcome was promising with a tailored locoregional multidisciplinary approach. Systematic lymph node dissection should be reconsidered in pediatric salivary gland tumors.

Impact of Pediatric Posterior Fossa Tumor Treatments on Working Memory Tracts Using Resting-State fMRI and Tractography.

Working memory, a primary cognitive domain, is often impaired in pediatric brain tumor survivors, affecting their attention and processing speed. This study investigated the long-term effects of treatments, including surgery, radiotherapy (RT), and chemotherapy (CT), on working memory tracts in children with posterior fossa tumors (PFTs) using resting-state functional MRI (rs-fMRI) and diffusion MRI tractography. This study included 16 medulloblastoma (MB) survivors treated with postoperative RT and CT, 14 pilocytic astrocytoma (PA) survivors treated with surgery alone, and 16 healthy controls from the Imaging Memory after Pediatric Cancer in children, adolescents, and young adults study (NCT04324450). Working memory tracts were identified by combining seed masks from rs-fMRI maps and whole-brain tractography from diffusion MRI. Connectivity alterations were assessed qualitatively and quantitatively, alongside neuropsychological evaluations and correlations with behavioral outcomes and mean supratentorial dose. Compared to controls, MB survivors exhibited significant impairments in the working memory network, including reductions in tract volume (TV), fiber density, fiber cross-section (FC), mean streamline length (MLS), and fractional anisotropy (FA) (all p = 0.04). Lower working memory scores were correlated with reduced TV and FA in MB survivors. Higher mean supratentorial doses were associated with lower TV, FC, and FA values across multiple tracts, particularly in the arcuate and superior longitudinal fasciculi. Tractography-derived features highlighted white matter damage as a biomarker of treatment-related neurotoxicity in PFTs survivors. These findings underscore the detrimental impact of RT and CT on working memory networks and emphasize the importance of preserving cognitive function during treatment planning.

Changing trends from inguinal radical orchiectomy to testis-sparing surgery in pediatric testicular tumors

Changing trends from inguinal radical orchiectomy to testis-sparing surgery in pediatric testicular tumors

Pediatric Neuroendocrine Tumors in Denmark: Incidence, Management, and Outcome From 1995 to 2020.

Neuroendocrine tumors (NETs), although rare, are considered one of the most common gastrointestinal and bronchopulmonary pediatric neoplasms. We aimed to determine the incidence, tumor characteristics, management, and outcome of NETs and explore the role of genetic predisposition, focusing on low and intermediate grade tumors. Using the Danish National Pathology Registry, we conducted a nationwide retrospective study including all Danish children aged ≤18 years diagnosed with a pathology-proven NET between 1995 and 2020. We identified 220 patients, with a 1.89:1 female to male ratio. The yearly incidence was 6.84 per 1 million children, with no significant change in incidence throughout the observation period. NETs were located in the appendix (93.2%), the pulmonary system (4.5%), and pancreas (2.3%). One recurrence was noted in the pancreas in a genetically predisposed patient with multiple neuroendocrine neoplasia type 1 (MEN1), resulting in an overall recurrence rate of 0.5% (0% in appendiceal NETs; 0% in bronchopulmonary NETs; 20.0% in pancreatic NETs). No NET-related mortality was registered. Four patients had a known predisposing genetic condition, one appendiceal NET associated with neurofibromatosis type 1, and three pancreatic NETs associated with MEN1. Postsurgical surveillance regimes, choice of tumor markers, and imaging modality varied throughout the study period. We confirmed a stable incidence of pediatric NETs during the study period. The overall recurrence rate was 0.5% and no NET-related mortality was observed. Known genetic predisposition was present in 1.8% of patients. Future guidelines should consider the apparent indolent nature and excellent prognosis of these tumors.

Advancements in Interoperability: Achieving Anatomic Pathology Reports That Adhere to International Standards and Are Both Human-Readable and Readily Computable.

Over the past 50 years, multiple pathology organizations worldwide have evolved in cancer histopathology reporting from subjective, narrative assessments to structured, synoptic formats using controlled vocabulary. These reporting protocols include the required data elements that represent the minimum set of evidence-based, clinically actionable parameters necessary to convey the diagnostic, prognostic, and predictive information essential for patient care. Despite these advances, the synoptic reporting protocols were not harmonized across the various pathology organizations. Cancer pathology continues to be widely reported and stored in free-text format, or without encoded data such that it is neither computable nor interoperable across organizations. In 2020, SNOMED International created the Cancer Synoptic Reporting Working Group (CSRWG). This resulted in international collaboration across multiple pathology organizations. CCRWG's mission was to use SNOMED Clinical Terms (CT) concepts to represent the required content within the College of American Pathologists (CAP) and International Collaboration on Cancer Reporting (ICCR) published pathology reporting protocols. In late 2023, the CSRWG published over 1,300 new or revised SNOMED CT concepts to represent all required pathology cancer data elements for adult and pediatric solid tumors in both CAP and ICCR using the semantic principles of the SNOMED-CT concept model. Thus, computability and interoperability would be broadly established. This work brings to fruition the longstanding desire for an international, interoperable, human- and machine-readable cancer pathology report for use in patient care, health care quality improvement, population health, public health surveillance, and translational and clinical trial research. The following report describes the project, its methods, and applications in the stated use cases.

Natural history study of patients with pancreatic acinar cell carcinoma: A 3-year prospective longitudinal analysis.

764 Background: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas that comprises 0.2-2% of all pancreatic malignancies. There are no prospective randomized studies in this disease and most data about PACC comes from retrospective database analyses and case reports. Methods: The Cancer Moonshot-funded My Pediatric and Adult Rare Tumor (MyPART) network’s Rare Solid Tumor Natural History study (NCT03739827) is a prospective, single-institution observational study that enrolls patients of all ages with rare solid tumors (&lt;15 cases per 100,000 people per year), including PACC. Patients can participate remotely (field cohort) or visit the NIH for annual evaluations (in-person cohort). All participants complete medical and family histories, patient reported outcomes (PROs) measures, and provide saliva for DNA analysis. Relevant data such as clinical and family histories, surgical and molecular pathology, and imaging results are extracted from patient medical records and entered in the central study database. Archival tumor samples (when available) are analyzed using a 500+ gene panel (TruSight500, Illumina) and discussed in a molecular tumor board. Patients participating in the in-person cohort undergo additional evaluations including clinical examination, imaging studies, genetic counseling, and blood sample collection for clinical and research purposes (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines) as indicated. Results: From 09/2021 until 09/2024, 17 PACC patients (n=13 for the field cohort, n=4 for the in-person cohort) were accrued. The mean age of diagnosis is 64.7 (48-78) years, and the male to female ratio is 14:3. At the time of diagnosis, 6 patients had Stage I or II, 1 had Stage III, and 10 had Stage IV disease. The median follow-up time since accrual is 7.6 months, and 4 patients have died. No patients have been lost to follow-up. Of the 6 patients diagnosed with early-stage disease, 5 had surgery and all received adjuvant chemotherapy, while 1 patient is receiving neoadjuvant chemotherapy. Among the 9 patients diagnosed with advanced disease, 8 received platinum-based regimens as a first-line therapy. Tumor molecular profiling was available for 16 patients. The most common tumor mutations observed were in CDKN2A (29.4%), BRCA2 (29.4%), and SMAD4 (23.5%). Six patients received targeted therapies matched to their tumor molecular profile. Conclusions: The demographic profile of our cohort aligns with previous studies, with a mean age of diagnosis in the early-to-mid 60s and a high male to female ratio. Our cohort highlights a shift in first-line treatment to platinum-based therapies over the past decade. Many PACC tumors have targetable mutations found in molecular profiling, and the efficacy of matched therapy warrants further exploration. Clinical trial information: NCT03739827 .

National virtual tumor boards to inform the management of children with rare cancers.

Due to the infrequent nature of rare pediatric cancers, rigorously studied treatment algorithms are usually nonexistent, and experience with a given tumor may be limited at a single institution. Development of treatment plans for these populations often requires extensive literature review and outreach to experts at other institutions. National or international virtual tumor boards provide a streamlined, collaborative approach to discussing diagnosis and management of these patients through dissemination of collective experience and knowledge. This review highlights current virtual tumor boards for rare pediatric cancers and their benefit as a resource for patient care. Over the last several years, national virtual tumor boards sponsored by government and academic institutions and cancer foundations have expanded access of pediatric oncologists to rare tumor expertise and guidance. Recommendations from these tumor boards often have an impact on medical decision making, and some serve as a resource for enduring educational reference materials. National virtual tumor boards are a valuable resource to clinicians caring for patients with rare pediatric tumors. These conferences provide real-time management advice from peers and subject matter experts and provide essential educational content not easily accessible in other formats.

Evaluation of Role of FNAC in Pediatric Kidney Tumors in a Tertiary Care Hospital

Evaluation of Role of FNAC in Pediatric Kidney Tumors in a Tertiary Care Hospital

A Retrospective Review of 28 Cases of Pediatric Malignant Renal Tumors at a Single Institution

A Retrospective Review of 28 Cases of Pediatric Malignant Renal Tumors at a Single Institution

Retraction Note: Comment on, "Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes".

Retraction Note: Comment on, "Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes".

Low rate of healing and high incidence of complications in benign pediatric bone tumors treated with synthetic calcium sulfate-calcium phosphate bone graft.

Synthetic calcium sulfate-calcium phosphate bioceramic composite has been developed as a material for bone grafting; however, the literature is limited on outcomes of benign bone tumors treated with bone grafting. This study aims to investigate the outcomes of benign pediatric bone tumors treated with a calcium sulfate-calcium phosphate composite bone graft. A retrospective review at a tertiary pediatric hospital with benign bone tumors treated with curettage and bone grafting with a calcium sulfate-calcium phosphate synthetic bone graft from 2008-2018 was included. Minimum follow-up was 6 months. Twenty-seven patients met inclusion criteria with a mean age of 10.3 ± 4.5 years and follow-up was 37.2 ± 22.3 months. Diagnoses were unicameral bone cysts (n = 16) and aneurysmal bone cysts (n = 11). Pathologic fracture was present in 48% (13/27) of patients on admission. All patients were treated using synthetic bone grafts and 37% (10/27) with internal fixation. Following index treatment, 96% (26/27) had resolution of pain and returned to full activity at 13.4 ± 10.7 weeks. Complications occurred in 33% (9/27) of patients; one developed chronic hip pain resulting in decreased physical activity, seven had a tumor recurrence without fracture, and one had tumor recurrence with pathologic fracture. Revision surgery was required in 26% (7/27) of cases. Per the modified Neer outcomes rating system, 52% of patients had a healed bone lesion, 4% had a healing lesion with a bone defect, and 44% had a persistent/recurrent cyst. Children with benign bone tumors treated with curettage and bone grafting using a calcium sulfate-calcium phosphate composite had a high incidence of complications and revision surgery. IV.

Analysis and Historical Evolution of Paediatric Bone Tumours: The Importance of Early Diagnosis in the Detection of Childhood Skeletal Malignancies

Even though children’s malignant bone tumours are rare, it is crucial to understand how to identify and stage them accurately to develop an appropriate treatment plan. Ewing’s sarcoma and osteosarcoma are the two main paediatric bone malignancies and require multidisciplinary treatment involving radiologists, orthopaedists, oncologists, pathologists, and paediatricians. These neoplasms may be associated with genetic syndromes but typically occur in patients with no known germline abnormalities. With a frequency of 4.4 per million, osteosarcoma is the most common malignant bone tumour in children. Ewing’s sarcoma has an incidence of 2.5 to 3 per million, making it the second most prevalent. Clinically, these neoplasms present with pain and inflammation in the bones and joints, nocturnal pain unresponsive to drug therapy, systemic symptoms such as fever or weight loss, and persistent symptoms—all of which should prompt clinicians to initiate further diagnostic investigations. The gold standard for diagnosis includes X-ray examination and MRI, which provide an accurate assessment of tumour extension into the medullary canal and surrounding soft tissues. Fluorine-18-labelled FDG-PET scans or fluoro-deoxyglucose positron emission tomography are valuable for evaluating tumour aggressiveness and excluding metastases. A biopsy is mandatory once all other diagnostic tests have been completed. Accurate diagnosis and timely referral to an experienced clinic are essential for ensuring prompt access to treatment and improving patient outcomes.

Development, optimization and application of a universal fluorescence multiplex PCR-based assay to detect BCOR genetic alterations in pediatric tumors

BackgroundA number of genetic aberrations are associated with the BCL6-correpresor gene (BCOR), including internal tandem duplications (ITDs) and gene fusions (BCOR::CCNB3 and BCOR::MAML3), as well as YWHAE::NUTM2, which are found in clear cell sarcoma of the kidney (CCSK), sarcoma with BCOR genetic alterations, primitive myxoid mesenchymal tumor of infancy, and high-grade neuroepithelial tumors in children. Detecting these gene aberrations is crucial for tumor diagnosis. ITDs can be identified by Sanger sequencing or agarose gel electrophoresis. However, gene fusions are usually detected through reverse transcription-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization. Methods that analyze these variants simultaneously in a sensitive and convenient manner are lacking in clinical practice.MethodsThis study validated a Universal Fluorescence Multiplex PCR-based assay that assessed BCOR ITDs, BCOR::CCNB3, BCOR::MAML3 and YWHAE::NUTM2 fusions simultaneously.ResultsThe assay achieved a detection threshold of 10 copies for fusion genes and 0.32 ng genomic DNA for BCOR ITDs. The performance of this assay was also tested in a cohort of 43 pediatric tumors (17 undifferentiated small round cell sarcomas, and 26 tumors with a histological diagnosis of CCSK). In total, 20 BCOR ITDs, 4 BCOR::CCNB3 and one YWHAE::NUTM2 were detected. When compared with the final diagnosis, the assay achieved 93% sensitivity and 100% specificity.ConclusionsAccordingly, this assay provided an effective and convenient method for detecting BCOR- and YWHAE-related abnormalities in tumors.

Diagnosis of pediatric melanocytic tumors

The histological diagnosis of pediatric melanocytic tumors is challenging, as benign nevi often resemble aggressive tumors. Accurate diagnosis is crucial for the early detection of rare pediatric melanomas. Recent advancements have established aclassification based on genetic backgrounds. This classification distinguishes between rarer subtypes and includes groups such as conventional melanomas, Spitz tumors, and melanomas arising from congenital melanocytic nevi. While the most common group, Spitz tumors, generally has afavorable prognosis, conventional melanomas and especially those arising from congenital nevi may exhibit an aggressive course similar to that of adult melanoma.

Editorial: Pediatric CNS tumors in low- and middle-income countries: expanding our understanding

Editorial: Pediatric CNS tumors in low- and middle-income countries: expanding our understanding