Evaluation of event-free survival as a surrogate for overall survival in genitourinary rhabdomyosarcoma.

Timely diagnosis is considered critical in pediatric oncology to optimize treatment outcomes, as delays may impact tumor extension and prognosis. We aimed to assess whether the time to diagnosis and treatment initiation for pediatric patients with rhabdomyosarcoma (RMS) improved over time in Italy and whether longer delays were associated with tumor extension and prognosis. We analyzed 749 pediatric patients diagnosed with RMS between 1996 and 2016. Diagnostic interval (DI) was defined as the number of days from symptom onset to diagnosis, while treatment interval (TI) was defined as the time from symptom onset to treatment initiation. DI was correlated with tumor characteristics at diagnosis, and TI was analyzed in relation to survival, using Kaplan-Meier analysis. The median DI was 32 days, showing a decreasing trend from 39.5 days in 1996 to 2000 to 30 days in 2011 to 2016. A longer DI was associated with age, unfavorable histology, and metastatic disease in univariate analysis, but these were not confirmed in multivariate analysis. The median TI was 48 days. Five-year event-free survival (EFS) and overall survival (OS) were 59.7% and 69.3%. In multivariate analysis, prognosis was negatively associated with age at diagnosis, unfavorable site, nodal involvement, and metastatic disease. TI was not associated with survival. In our national cohort, the time from symptom onset to diagnosis showed a trend toward shortening in recent years. While a timely diagnosis can provide clarity on the child's condition and potentially reduce parental anxiety, it does not substantially impact tumor characteristics or patient outcomes.

Primary gastric alveolar rhabdomyosarcoma (RMS) is an extremely rare condition. We report a case of a 32-year-old man who presented with abdominal distension and anorexia. Imaging revealed a gastric mass with peritoneal dissemination and vertebral metastasis. Endoscopy revealed a large, ulcerative lesion. Histopathology revealed small round cells in an alveolar pattern that were positive for desmin and myogenin. Despite the initiation of multimodal therapy, the patient developed septic shock and died 10 days after treatment. This case highlights the aggressive nature of primary gastric alveolar RMS and emphasizes the importance of integrated diagnostic approaches, including histopathological, immunohistochemical, and molecular analyses, for its accurate diagnosis and appropriate management.

Malignant transformation of intracranial nongerminomatous germ cell tumors (NGGCTs) is a rare but clinically relevant phenomenon. We present the case of a 13-year-old boy with a localized, pineal NGGCT. After an initial favorable response, tumor growth was noted while still on chemotherapy. Histopathologic characterization revealed that 40% of the tumor was embryonal rhabdomyosarcoma (RMS), consistent with potential malignant transformation. Due to the rare nature of NGGCT malignant transformation, the best clinical approach to these cases remains unclear. We explore existing cases, treatments, and outcomes of malignant transformation in intracranial NGGCTs to help inform future clinical decision-making and the establishment of treatment guidelines.

<div><table cellspacing="0" cellpadding="0" align="left"><tbody><tr><td align="left" valign="top"><p><em>Ureteral Rhabdomyosarcoma (RMS) in children is a rare malignancy that may involve the ureter, leading to obstruction and hydronephrosis. Management requires a combination of oncologic therapy and individualized surgical planning, particularly when tumor resection results in extensive ureteral defects. This case report describes an 8-year-old girl with pelvic embryonal RMS involving the right distal ureter, previously treated with pelvic radiotherapy and VAD (vincristine, actinomycin, and doxorubicin) chemotherapy. Imaging showed tumor compression of the distal ureter with grade III hydronephrosis. Surgical resection necessitated en bloc distal ureterectomy, creating a 10-cm ureteral defect. Due to prior pelvic radiation and concerns regarding bladder fibrosis and metabolic complications from bowel interposition, ureteral substitution using the appendix was performed. Postoperative recovery was uneventful, with stable renal function, normal electrolyte balance, and no urinary leakage. Follow-up imaging at 6 months demonstrated a well-functioning appendiceal conduit and no residual tumor. This case illustrates that appendiceal ureteral substitution can be a safe and effective reconstructive option for long distal ureteral defects in pediatric RMS, particularly when prior radiation limits alternative techniques. Careful surgical technique and close follow-up remain essential to ensure optimal outcomes</em></p><p><em> </em></p></td></tr></tbody></table></div><p><strong><em>Keywords: Ureteral Substitution, Ureteral Reconstruction, Appendix, Embryonal Rhabdomyosarcoma</em></strong></p><p> </p>

Rhabdomyosarcoma (RMS) of the prostate is a rare tumor in infants. RMS frequently arises in genitourinary tract (~20% of cases), with the embrional subtype being the most common.1,2 The presenting symptoms are usually not specific, often leading to an extensive diagnostic work-up before identifying RMS.3,4 Furthermore, there are no biomarkers specific to RMS. We present the case of a 4-month-old boy with postrenal acute kidney injury (AKI). Abdominal ultrasound and magnetic resonance imaging (MRI), followed by ultrasound-guided fine-needle aspiration biopsy and citopathological examination, established the diagnosis of prostatic RMS, which was later staged with 18F-FDG PET/CT.5

This case series presents two cases of rhabdomyosarcoma (RMS), a rare malignancy of mesenchymal origin that accounts for 5% of all paediatric cancers and is extremely rare to present in adults. It can develop in various sites, including the head and neck, thorax, liver, biliary tract, retroperitoneum, urinary bladder, vagina, extremities, and paratesticular locations. Herein we present a case series of intrabdominal RMS, comprising the first case, an intraperitoneal RMS in a 2-year-old male child, and the second case, a retroperitoneal RMS in a 22-year-old male. Intraperitoneal RMS is extremely rare. Intraperitoneal and retroperitoneal RMS are aggressive tumours and have a poor prognosis. Both cases were of the spindle cell type of RMS, which is the most uncommon type.

Background: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, but primary RMS of the breast is exceptionally rare and diagnostically challenging. Imaging findings are nonspecific and can mimic benign adolescent lesions (e.g., fibroadenoma), making timely histopathologic confirmation crucial. Immunohistochemistry for muscle markers—particularly Desmin and Myogenin—supports definitive diagnosis of embryonal RMS (ERMS). Case Presentation: A 14-year-old Arab female presented with a rapidly enlarging left-breast mass and ipsilateral axillary lymphadenopathy. Core biopsy showed small round blue cells with rhabdomyoblastic differentiation; tumor cells were Desmin- and Myogenin-positive, consistent with ERMS. She received six cycles of MAID chemotherapy, followed by local recurrence; one cycle of ICE achieved ~50% partial response but was complicated by cystitis and rapid radiologic progression. After three cycles of VAC, she underwent total mastectomy with lymph-node dissection. Restaging FDG-PET/CT demonstrated local recurrence and nodal metastases (bilateral axillary, subpectoral, internal mammary) with pulmonary nodules. Despite multimodal therapy, the disease remained refractory and the patient ultimately died of complications from metastatic RMS. Case Discussion: This case highlights the aggressive biology of primary breast ERMS in adolescents and the risk of early recurrence and dissemination despite intensive therapy. While standard management of RMS is multimodal—systemic chemotherapy with surgical resection and/or radiotherapy—responses can be transient, and treatment interruptions (e.g., toxicity-related delays) may jeopardize disease control. The diagnostic value of Myogenin (highly specific for rhabdomyoblastic differentiation) and Desmin was pivotal here, while the clinical course underscores the limitations of currently available regimens (MAID, ICE, VAC) for refractory disease at this uncommon site. Conclusion: Primary embryonal RMS of the breast is rare and highly aggressive, with a strong propensity for local recurrence and metastatic spread. Even with aggressive multimodal therapy, outcomes can be poor. Earlier recognition, rigorous treatment delivery, and development of novel strategies are urgently needed to improve survival in this devastating presentation.

Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease (HFMD), and this virus exhibits substantial genetic diversity. To clarify its genomic evolutionary features, this study conducted a phylodynamic analysis on EV-A71 viruses collected in Qingdao (a northern Chinese city) between 2023 and 2024. EV-A71 was identified using a commercial real-time quantitative PCR (qPCR) assay; EV-A71-positive samples were then inoculated into rhabdomyosarcoma (RD) cells for virus isolation. The complete genome sequences and VP1 gene sequences of EV-A71 strains were amplified and analyzed, with IQ-TREE, SimPlot, and RDP4 software used to evaluate their evolutionary characteristics. Among 2,083 clinical samples, 27 were EV-A71-positive, with 19 isolates successfully cultured. Whole-genome analysis confirmed the co-circulation of EV-A71 genotypes C4 (5 strains) and B5 (14 strains). The C4 strains showed high homology to a strain isolated in China in 2019 and carried six lineage-specific mutations. In contrast, the B5 strains clustered into two distinct lineages, including recombinants that had undergone genetic recombination with coxsackievirus A4 (CV-A4) and coxsackievirus A2 (CV-A2). Notably, all EV-A71 strains collected from Qingdao maintained a serine (S) at the 17th amino acid residue of the VP1 region. This work enhances our understanding of the geographical distribution of EV-A71 by confirming the sustained circulation of genotype B5 in northern China and identifying a novel C4/B5 co-circulation pattern in Qingdao—a pattern reflecting complex local evolutionary dynamics. It emphasizes expanding genomic sequencing coverage to monitor B5 and recombinant strains, refining surveillance, and guiding HFMD prevention and control.

Ovarian Sertoli-Leydig cell tumor (SLCT) with heterologous rhabdomyosarcoma (RMS) is exceptionally rare. While the presence of heterologous elements in SLCT is highly predictive of an underlying DICER1 mutation, the molecular alterations in these tumors, including in SLCTs with heterologous RMS, remain largely unknown. In this study, we aimed to characterize the clinicopathologic features of these rare tumors, and in a subset of cases, we analyzed in detail their molecular changes to investigate potential recurrent and component-specific genetic alterations. We report clinicopathologic features of 11 ovarian SLCTs with heterologous RMS (positivity for desmin and myogenin); 10 were in keeping with embryonal and 1 with pleomorphic RMS. The patients showed a bimodal age distribution: seven patients (64%) were aged 33 years or younger (mean 20) and four patients (36%) were aged 52 years or older (mean 60). All tumors were unilateral. In addition to the RMS components, 8 of 11 cases (73%) contained other heterologous elements, including gastrointestinal-type mucinous epithelium (5 cases) and immature cartilage (3 cases). Seven of 11 cases (64%) underwent next-generation sequencing analysis. All tumors tested molecularly (7/7, 100%) harbored hotspot DICER1 mutations. Of these, six cases (86%) also carried a second nonsense or frameshift loss-of-function DICER1 mutation. One case had only a p.D1810Y hotspot mutation and consisted of high-grade sarcoma with focal rhabdomyoblastic differentiation (focal expression of desmin and myogenin) in keeping with pleomorphic RMS; the pleomorphic sarcoma component also exhibited mutation-type p53 expression. In addition to DICER1 mutations, TERT c.-124C>T promoter (4 cases) or TP53 mutations (3 cases) were present in all cases and were mutually exclusive. Component-specific analysis in two cases revealed shared common DICER1 hotspot mutations in both the SLCT and RMS components, supporting a clonal origin. In 1 case, a TERT promoter c.-124C>T somatic mutation was present only in the RMS component. In the other case, the TERT promoter mutation was found in both components, while a BRAF p.V600E mutation was exclusive to the RMS component. Our study demonstrates that the majority (86%) of SLCTs with heterologous RMS harbor double DICER1 mutations (a hotspot mutation and a nonsense or frameshift loss-of-function mutation), supporting the existing knowledge on DICER1 mutations associated with RMS heterologous elements, the presence of which should trigger genetic counselling. Our findings also suggest that molecular alterations other than DICER1, namely, TERT promoter and TP53 mutations, may contribute to component-specific oncogenic transformation.

A BSTRACT Urachus is a tubular remnant connecting the bladder’s apex to the umbilicus, where urine initially drains in the fetus during embryonic development. We report a rare case of a 7-year-old boy presenting with an asymptomatic lower abdominal lump. Physical examination revealed a nontender hypogastric mass. Contrast-enhanced computed tomography scan was suggestive of a large abdominopelvic mass abutting the anterior abdominal wall. Ultrasound-guided percutaneous biopsy followed by a histological analysis with immunohistochemistry showed embryonal rhabdomyosarcoma (RMS). Further metastatic workup ruled out distant metastasis. The patient received neoadjuvant chemotherapy followed by surgical excision. The tumor was primitively related to the urachus and involved the serosal surface of the bladder dome without detrusor infiltration, suggestive of the urachal RMS. Total macroscopic resection of the urachal mass with partial cystectomy was performed. The child underwent adjuvant chemoradiotherapy in the postoperative period without any recurrence at 1-year follow-up.

Olaparib and temozolomide (OT) combination therapy is in clinical trial evaluation for rhabdomyosarcoma (RMS). Unfortunately, OT resistance has been reported in other cancers. Using preclinical mouse xenograft experiments, we show that OT effectively suppresses RMS growth, yet over half of RMS tumors develop resistance associated with transcriptomic changes that occur in the absence of recurrent genomic mutation. Importantly, most resistant RMS models upregulate the PIK3CA/AKT pathway, activating NRF2 phosphorylation and subsequent transcriptional expression of multidrug resistance ABC transporters. PIK3CA inhibitor alpelisib re-sensitizes resistant cells to OT by suppressing expression of ABC transporters. The combination of OT + alpelisib also kills RMS cells which are resistant to standard-of-care combination chemotherapy and was effective in preclinical xenograft mouse models at curbing tumor growth. Our work defines a common resistance pathway in RMS and has credentialled PIK3CA/AKT inhibition as a preclinical strategy to kill therapy resistant RMS.

BackgroundHand, foot, and mouth disease (HFMD) is a widespread infectious disease primarily affecting infants and young children. Enterovirus A71 (EV-A71) comprises eight genogroups, among which subgroup C4 is the dominant viral agent in China and is frequently associated with HFMD and central nervous system infections. The genetic characteristics of an EV-A71 subgroup C4 strain obtained in this study were analyzed using whole-genome sequencing. Its biological characteristics, including infectivity, replication, and cytotoxicity, were investigated in human rhabdomyosarcoma (RD) and African green monkey kidney (Vero) cells.MethodsA clinical EV-A71 C4 subgourp GD10 strain isolated in China was examined to evaluate its genetic and biological features. Its relationships with strains listed in GenBank were evaluated using phylogenetic analysis. Viral infectivity and replication were assessed in RD and Vero cells. Cytotoxicity was evaluated by measuring cell viability, lactate dehydrogenase (LDH) release, and ATP levels. Effects on blood–brain barrier (BBB) integrity were investigated in vitro by assessing transendothelial electrical resistance and viral load across the barrier.ResultsSequence analysis confirmed that GD10 belonged to subgroup C4 and closely resembled strains from China. GD10 infection induced a pronounced cytopathic effect and elevated viral RNA levels in RD cells but not in Vero cells. The infection time-dependently increased LDH release and reduced ATP levels. GD10 compromised BBB integrity and crossed the cellular barrier in vitro.ConclusionThe GD10 strain demonstrated strong adaptability to RD cells and impaired BBB function. Our results improve the understanding of virus–host interactions and may support efforts towards EV-A71 vaccine development.Clinical TrialNot applicableSupplementary InformationThe online version contains supplementary material available at 10.1186/s12879-025-12241-2.

Abstract Li-Fraumeni Syndrome (LFS), caused by pathogenic germline Tp53 mutations, is a pediatric cancer predisposition disorder associated with markedly elevated risk of early-onset tumors, particularly rhabdomyosarcoma (RMS). Our study examined how developmental disruption may prime the tissues of LFS individuals for tumorigenesis. Single-nuclei RNA sequencing (snRNA-seq) was performed on RMS tumors, distal muscle from mice matched to RMS tumors, and cancer-free WT and LFS mouse muscle to define lineage-specific transcriptomic signatures of LFS-RMS. Embryonic limb buds were collected at embryonic days 10, 12, 14, and 16, subjected to snRNA-seq, and used to reconstruct developmental trajectories. These lineage-specific signatures were mapped back onto both WT and LFS embryonic lineages to determine whether oncogenic programs were detectable in utero and to identify the timing of their emergence. A stress-primed transcriptional program was identified as a defining feature of LFS tissues. This program distinguished precancer from postcancer states, becoming amplified in both RMS tumors and distal muscle matched to tumors. In LFS embryos, stage-specific alterations were observed in cell type proportions and maturation, including the emergence of unique myogenic and mesenchymal subpopulations absent in both WT embryos and postnatal muscle, reflecting developmental plasticity restricted to the LFS embryonic context. A lag in the transition to mature myogenic cells was detected at E14, preceded by a spike in the LFS stress-primed signature at E12 during windows of active lineage specification and proliferation. Pathway analyses of lineage-specific signatures indicated widespread dysregulation, with particularly strong changes in RNA-associated and developmental programs, further defining this stress-sensitive transcriptional state. These findings provide the first single-nuclei resolution map of embryogenesis in LFS and provide evidence that LFS-associated oncogenic programs are prenatally encoded. By linking altered lineage dynamics, developmental plasticity, and stress-primed transcriptional states to the emergence of RMS, this work establishes a developmental framework for understanding pediatric cancer predisposition. The results highlight potential windows for early detection and suggest opportunities to target embryonically primed programs for intervention in LFS. Citation Format: Ashby Kissoondoyal, Paula R. Quaglietta, Brianne Laverty, David Malkin. Single-nuclei profiling of LFS development reveals tumour susceptibility [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr B033.

Didox, a ribonucleotide reductase inhibitor with iron chelator properties, counteracts the in vitro and in vivo growth of rhabdomyosarcoma cells.

Impact of extensive surgery in a multidisciplinary approach of parameningeal rhabdomyosarcoma in children, adolescent and young adult population.

MRI Based Intratumoral-Peritumoral Habitat Radiomics for Prediction of Overall Survival in Rhabdomyosarcoma: A Multicenter Study.

At least one-third of patients with localized rhabdomyosarcoma (RMS) and 60-70% of patients with metastatic RMS experience progressive disease or relapse. Following relapse, outcomes generally remain poor with limited treatment options and a high risk of subsequent recurrence. Optimal treatment requires a multidisciplinary approach incorporating chemotherapy with local control. Given the complexity of managing relapsed RMS and the challenges in developing effective treatment strategies, we aim to present clear and practical recommendations on the management of these patients across Europe. These recommendations were developed collaboratively by a group of pediatric and adolescent sarcoma experts from the European paediatric Soft Tissue Sarcoma Study Group. A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Such recommendations provide a standardized approach to managing relapsed cases, improving patient outcomes and offering a framework for clinicians to make informed decisions.

PAX3-FOXO1+ rhabdomyosarcoma cells and tumors exhibit increased sensitivity to DHFR inhibition via methotrexate, identifying a potential therapeutic vulnerability that can be exploited to treat this aggressive pediatric sarcoma.

MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators and influence the development and progression of several cancers, yet their roles in pediatric sarcomas remain poorly defined. RNA extracted from formalin-fixed paraffin-embedded tumor tissue scrolls of 108 pediatric tumors, including 32 osteosarcoma (OS), 26 Ewing's sarcoma (EWS), and 50 rhabdomyosarcoma (RMS) cases, were analyzed for microRNA expression using the NanoString multiplex nCounter platform that yielded information on 827 human miRNAs. The expression of candidate miRNAs was validated with in situ hybridization (miRNA-ISH) and QuPath quantification on tissue microarray slides comprising an independent set of 48 OS, 17 EWS, and 104 RMS adult and pediatric cases collectively. The differential expression analysis of nCounter data identified 23 miRNAs enriched in RMS, 33 in EWS, and 45 in OS (>3 fold change and p < 0.01). miR-206 was most strongly associated (>55 fold change, p < 1 × 10-9) with RMS and demonstrated the highest sensitivity and specificity in distinguishing RMS from EWS and OS; this finding was also confirmed by miRNA-ISH. A combined signature of differentially expressed miRNAs reliably separated alveolar from embryonal RMS. The expression of miR-9-5p in EWS and miR-140-5p in OS discriminated among the different tumors and correlated with adverse patient outcome. The nCounter assay exhibited greater sensitivity than miRNA-ISH in detecting miR-206 and miR-140-5p expression. Collectively, these findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and subtypes and offer clinically relevant insights into tumor biology, prognosis, and potential diagnostic application.