Common Pediatric Tumor Research Articles

Aberrant activation of wound healing programs within the metastatic niche facilitates lung colonization by osteosarcoma cells.

Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. The purpose of this study is to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms underlying osteosarcoma lung metastatic niche formation. Using single-cell transcriptomics (scRNA-seq), we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multi-parameter immunofluorescence and spatial transcriptomics. Based on these findings, we evaluated the ability of nintedanib, a kinase inhibitor used to treat patients with pulmonary fibrosis, to impair metastasis progression in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Single-nucleus and spatial transcriptomics was used to perform molecular pharmacodynamic studies that define the effects of nintedanib on tumor and non-tumor cells within the metastatic microenvironment. Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. scRNA-seq demonstrated that the surrounding lung stroma adopts a chronic, non-resolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, metastasis-associated lung demonstrated marked fibrosis, likely due to the accumulation of pathogenic, pro-fibrotic, partially differentiated epithelial intermediates and macrophages. Our data demonstrated that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis. Fibrosis represents a targetable vulnerability to block the progression of osteosarcoma lung metastasis. Our data support a model wherein interactions between osteosarcoma cells and epithelial cells create a pro-metastatic niche by inducing tumor deposition of extracellular matrix proteins such as fibronectin that is disrupted by the anti-fibrotic TKI nintedanib. Our data shed light on the non-cell autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKI on metastases in animal models.

IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma

BackgroundHepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated.MethodsThis study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.ResultsThe study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.ConclusionThe overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.ImpactThe present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

PL3 CendR peptide shows specific uptake in cultured Y79 retinoblastoma cells with nucleolar accumulation

Retinoblastoma is the most common pediatric intraocular malignant tumor affecting 1:15 000–1:20 000 live births. Even though the survival rate in developed countries is over 90 %, more efficient treatment options are needed for better vision salvage and reduction of the adverse effects. Therefore, we investigated fluorescein-labeled PL3 peptide targeting properties towards the Y79 retinoblastoma cell line in vitro. Through the application of cellular imaging and flow cytometry techniques, the PL3 peptide exhibited a rapid and specific internalization within Y79 cells, with subsequent translocation to the cell nuclei, showcasing notable accumulation in the nucleoli. This phenomenon was not present in other investigated cell lines and was not observable with similarly charged and length control peptide. However, the exact mechanism behind this Y79 cell line-specific nuclear and nucleolar targeting pattern remains elusive. In the future, this targeting process could facilitate specific treatment modalities of retinoblastoma with PL3 peptide-coupled drug delivery technologies.

Additional value of CMR parametric mapping in tissue characterization of common benign pediatric cardiac tumors.

Cardiac Magnetic Resonance (CMR) parametric mapping is underexplored in cardiac tumors. To evaluate the contribution of mapping sequences on the characterization of pediatric tumors. All pediatric patients referred for cardiac tumors at Bambino Gesù Children's Hospital from June 2017 to November 2023, who underwent CMR with mapping sequences, were included. The diagnosis of tumor type was performed according to signal characteristics on different sequences. Mass parametric mapping for each subtype and interobserver variability was assessed. Sixteen patients were enrolled. The mean age at CMR was 7 ± 5 years. "Traditional" mass-type assessment diagnosed hemangioma (Group A) in 3 patients (19%), fibroma (Group B) in 4 patients (25%), rhabdomyoma (Group C) in 6 patients (37%), and lipoma (Group D) in 3 patients (19%). The ANOVA analysis revealed significant differences in mass native T1 and mass extracellular volume (ECV) values among the four subgroups (p<0.001 for both comparisons). The mean native T1 and ECV values were respectively 1465 ± 158 msec and 54 ± 4% for Group A, 860 ± 118 msec and 93 ± 4% for Group B, 1007 ± 57 msec and 23 ± 5% for Group C, and 215 ± 13 msec and 0 ± 0% for Group D. Mass mapping analysis is feasible and reproducible in children. ECV values provide the most accurate differentiation. Mass ECV consistently resembles normal myocardium in rhabdomyoma, is extremely high (approaching 100%) in fibroma, equals to zero in lipoma, and matches blood pool ECV (1-Hct) in hemangioma.

Minimally invasive and robotic-assisted approaches applied to pediatric surgical oncology.

The management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.

Rhabdoid Differentiation in Wilms Tumor

ABSTRACT Wilms tumor (WT) is a relatively common pediatric tumor. Depending on the stage of disease, treatment includes surgery, chemotherapy, and radiotherapy. Chemotherapy and radiotherapy can induce differentiation of tumor cells to rhabdoid morphology that can masquerade as rhabdoid tumor of the kidney. We report a rare case of WT with rhabdoid differentiation subsequent to treatment with neoadjuvant chemotherapy. Rhabdoid tumor of the kidney was initially considered a sarcomatous variant of WT, however was later classified separately due to distinct behavior. This makes it challenging to differentiate from WT with rhabdoid differentiation which is important as that would also affect the aggressiveness of treatment and prognosis.

Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours

BackgroundCertain paediatric nervous system malignancies have dismal prognoses. Retinoic acid (RA) is used in neuroblastoma treatment, and preclinical data indicate potential benefit in selected paediatric brain tumour entities. However, limited single-agent efficacy necessitates combination treatment approaches.MethodsWe performed drug sensitivity profiling of 76 clinically relevant drugs in combination with RA in 16 models (including patient-derived tumouroids) of the most common paediatric nervous system tumours. Drug responses were assessed by viability assays, high-content imaging, and apoptosis assays and RA relevant pathways by RNAseq from treated models and patient samples obtained through the precision oncology programme INFORM (n = 2288). Immunoprecipitation detected BCL-2 family interactions, and zebrafish embryo xenografts were used for in vivo efficacy testing.ResultsGroup 3 medulloblastoma (MBG3) and neuroblastoma models were highly sensitive to RA treatment. RA induced differentiation and regulated apoptotic genes. RNAseq analysis revealed high expression of BCL2L1 in MBG3 and BCL2 in neuroblastomas. Co-treatments with RA and BCL-2/XL inhibitor navitoclax synergistically decreased viability at clinically achievable concentrations. The combination of RA with navitoclax disrupted the binding of BIM to BCL-XL in MBG3 and to BCL-2 in neuroblastoma, inducing apoptosis in vitro and in vivo.ConclusionsRA treatment primes MBG3 and NB cells for apoptosis, triggered by navitoclax cotreatment.

Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation

BackgroundWilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.MethodsDifferential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes’ functions in WiT-49 cells.ResultsThe enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients’ prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.ConclusionsEMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Tumor-associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target.

The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM-derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics. Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage-mediated antibody-dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR Mφ) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.

Staging and Restaging Pediatric Abdominal and Pelvic Tumors: A Practical Guide.

The most common abdominal malignancies diagnosed in the pediatric population include neuroblastoma, Wilms tumor, hepatoblastoma, lymphoma, germ cell tumor, and rhabdomyosarcoma. There are distinctive imaging findings and patterns of spread for each of these tumors that radiologists must know for diagnosis and staging and for monitoring the patient's response to treatment. The multidisciplinary treatment group that includes oncologists, surgeons, and radiation oncologists relies heavily on imaging evaluation to identify the best treatment course and prognostication of imaging findings, such as the image-defined risk factors for neuroblastomas, the PRETreatment EXtent of Disease staging system for hepatoblastoma, and the Ann Arbor staging system for lymphomas. It is imperative for radiologists to be able to correctly indicate the best imaging methods for diagnosis, staging, and restaging of each of these most prevalent tumors to avoid inconclusive or unnecessary examinations. The authors review in a practical manner the most updated key points in diagnosing and staging disease and assessing response to treatment of the most common pediatric abdominal tumors. ©RSNA, 2024 Supplemental material is available for this article.

Evaluation of surgical strategies and long-term outcomes in pediatric hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1years (0.8-16.4years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.

Abstract 1121: Targeting the DNA damage response in high-risk medulloblastoma

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumour and is currently treated with surgery, external beam radiation and chemotherapy however, current treatments are woefully inadequate, with survival of only 50% but morbidity approaching 100%. A very-high risk group of SHH-activated MB harboring TP53 mutations (TP53mut-SHH) account for a substantial proportion of treatment failures after radiotherapy with a uniformly fatal outcome. Through optimizing radiation as a selection pressure and employing a functional genetic approach through whole-genome CrisprCas-9 dropout screening, the present study aims to identify drivers of radiation resistance and uncover unique vulnerabilities to sensitize these tumours to therapy. The dropout screen was conducted across a panel of established in vitro models of sporadic murine TP53mut-SHH, which resemble the human disease with profound radio-resistance. Initial results reveal that targeting the DNA damage response confer radiation sensitization. However, consistent hits across all models demonstrate non-homologous end-joining (NHEJ) as being synthetically lethal with radiation specifically in TP53mut-SHH. Genetic knockout experiments confirm genes encoding main proteins involved in NHEJ are synthetically lethal in combination with radiation. A small molecule drug screen targeting NHEJ revealed such vulnerabilities may be therapeutically exploited in TP53mut-SHH and are able sensitize these tumours to radiation. Using our unique approach of leveraging newly established models of TP53mut-SHH with a combination of functional genetic screening and small-molecule drug screening, this study highlights the genetic mechanisms of treatment resistance and reveals novel approaches for radiation sensitization. Here, we develop a novel approach to identify targets that are synthetically lethal with radiotherapy and identify multiple synthetically lethal targets at the genetic level which can be therapeutically targeted, allowing the development of new treatments to overcome current barriers. Citation Format: Alexandria DeCarlo, Carolina Fernandes da Silva, Lily Shen, Vijay Ramaswamy, Uri Tabori. Targeting the DNA damage response in high-risk medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1121.

Abstract 1101: A patient-derived xenograft in vitro platform identifies panobinostat as the most efficient drug to treat high-risk hepatoblastoma patients

Abstract Hepatoblastoma is the most common pediatric liver tumor, and the treatment of patients with preoperative chemotherapy and surgical resection of the tumor has led to survival rates of up to 83%. However, resistance of the primary tumor towards chemotherapy and the persistence of metastases still represents major challenges to achieve complete remission in high-risk patients, which is associated with poor prognosis. In order to identify new treatment options, we have used a newly developed in vitro drug-testing platform comprised of conventional cell lines and cultures from dissociated patient-derived xenografts of pediatric liver cancers to test standard-of-care medications used in the current PHITT trial as well as compounds targeting a wide range of different cellular pathways. We identified histone deacetylase (HDAC) inhibitors as a promising drug family to reduce tumor cell growth in a dose-dependent manner, with panobinostat being the most effective drug tested. Subsequent in vitro assays showed that panobinostat reduced short- and long-term proliferation, retarded three-dimensional spheroid growth and ultimately induced apoptosis of hepatoblastoma cells. RNA sequencing indicated that panobinostat results in downregulation of MYC target genes and upregulation of the dual specificity phosphatase 1. Of clinical relevance, the combination of panobinostat with doxorubicin revealed a strong synergistic effect, even stronger than the one of cisplatin and doxorubicin, which is currently given to high-risk hepatoblastoma patients. Moreover, increased expression of HDAC4 and HDAC11 in primary tumor tissues was significantly associated with metastatic disease. Our results strongly suggest panobinostat to be used in future therapeutic trials for high-risk hepatoblastoma patients, especially when combined with doxorubicin. Citation Format: Salih Demir, Emilie Indersie, Sophie Branchereau, Eiso Hiyama, Stefano Cairo, Roland Kappler. A patient-derived xenograft in vitro platform identifies panobinostat as the most efficient drug to treat high-risk hepatoblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1101.

Growing Pains: A Rare Case of a Temporal Dermoid Cyst in an Adult and Review of the Literature

Dermoid cysts are common cutaneous developmental anomalies that occur due to the entrapment of ectodermal elements during embryonic closure. While the exact origin of dermoid cysts is unknown, they are theorized to originate from multipotent embryonic stem cells or translocated epithelial cells. Dermoid cysts are typically congenital but are sometimes diagnosed later in childhood and rarely in adulthood. They are reported as the most common pediatric skull tumors. Surgical excision is recommended to prevent enlargement, invasion, rupture, or infection. Temporal dermoid cysts, specifically, are extremely rare, with only a few cases having been reported in adulthood. We present a case of a 51-year old female with an enlarging left temporal mass found to be a dermoid cyst. The mass was excised, resulting in complete resolution of symptoms. This case highlights the importance of early excision, radiologic studies, and a tailored management approach based on cyst location. Our proposed treatment algorithm provides guidance for clinicians in identification and management of adult dermoid cysts.

Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience.

Cardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.

Spatial sequestration of activated-caspase 3 in aggresomes mediates resistance of neuroblastoma cell to bortezomib treatment

Neuroblastoma (NB) is the most common pediatric tumor and is currently treated by several types of therapies including chemotherapies, such as bortezomib treatment. However, resistance to bortezomib is frequently observed by mechanisms that remain to be deciphered. Bortezomib treatment leads to caspase activation and aggresome formation. Using models of patients-derived NB cell lines with different levels of sensitivity to bortezomib, we show that the activated form of caspase 3 accumulates within aggresomes of NB resistant cells leading to an impairment of bortezomib-induced apoptosis and increased cell survival. Our findings unveil a new mechanism of resistance to chemotherapy based on an altered subcellular distribution of the executioner caspase 3. This mechanism could explain the resistance developed in NB patients treated with bortezomib, emphasizing the potential of drugs targeting aggresomes.

Extra-axial desmoplastic/nodular medulloblastoma in adult mimicking cerebellar metastasis: reappraisal of this rare presentation with literature review

Introduction and importance: Medulloblastomas are the most common malignant intra-axial brain tumour in paediatric patients and represent 35–40% of posterior fossa tumour types in children between 3 and 9 years of age. Medulloblastomas may also be found in adulthood. These tumours are classified into two groups according to its molecular characteristics and histological type. The desmoplastic/nodular subtype is the second common subtype after the classic one. Only three cases of desmoplastic/nodular extra-axial medelloblastoma have been previously reported in the literature originating from to the cerebellopontine angle. Case presentation: The authors report a new case of an extra-axial desmoplastic/nodular cerebellar medulloblastoma originating outside the cerebellopontine angle and mimicking a solitary cerebellar metastasis in a 49-year-old female patient who presented for a raised intracranial pressure and cerebellar syndrome. Clinical discussion: Medulloblastoma is a malignant embryonal intra-axial tumour of the cerebellum or posterior brain stem that occurs mainly in children. Medulloblastomas may also be found in adulthood. Desmoplastic/nodular medulloblastoma is the second most common type of all medulloblastomas. The intra-axial form is always predominant. Only three cases of extra-axial desmoplastic/nodular medulloblastoma have been reported in the literature. The authors will go through the literature to dissect this rare entity. Conclusion: Although considered a common paediatric intra-axial tumour, there are increasing numbers of solitary cases reporting an extra-axial presentation in different locations of the posterior cerebral fossa even in adulthood. These rare and unusual presentations and locations may mislead the correct diagnosis and delay treatment.

Primary extragonadal yolk sac tumor of the orbit: A rare case and review of literature

Germ cell tumors usually arise from primordial cells in gonads, mainly testes, and ovaries. Extragonadal involvement of orbit is very unusual. We report one case of primary yolk sac tumor of orbit in a 3-year-old male child presented as a left lateral orbital mass. Its clinical presentation may mimic many common pediatric orbital tumors causing misdiagnosis which affects ocular morbidity and mortality. Awareness about this rare entity to clinicians is helpful in the early diagnosis and proper management of young kids.

Pediatric Brainstem Tumor Biopsy: Surgical Planning and Execution for Maximal Safety and Tissue Yield.

Brainstem tumors account for 10-20% of pediatric brain tumors with a peak age of diagnosis between 7 and 9years old and are often fatal. Historically, diagnosis of brainstem tumors has been largely based on imaging; however, recent studies have demonstrated the incongruities between preoperative MRI diagnosis and postoperative pathological findings highlighting the importance of brainstem biopsy for diagnostic accuracy. Stereotactic brainstem biopsy for pediatric brainstem tumors has been proven to be safe with a high diagnostic yield (96.1-97.4%) and relatively low morbidity and mortality. Successful pediatric brainstem tumor biopsy demands intricate knowledge of brainstem anatomy, cranial nerves and vasculature, and common pediatric brainstem tumors by the performing surgeon. Additionally, understanding of the surgical indications and techniques (e.g., frame-based versus frameless, robotic assistance, surgical approach, and targets selection) helps to ensure maximal safety and tissue yield. Pediatric brainstem biopsy permits histological conformation of brainstem lesions leading to accurate diagnosis and the potential for personalized treatment and future therapeutic research.

Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas.

Sarcomas comprise between 10-15% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma are the two most common pediatric bone tumors diagnosed in children and young adults. These tumors are commonly treated with surgery and/or radiation therapy and combination chemotherapy. However, there is a strong need for the development and utilization of targeted therapeutic methods to improve patient outcomes. Towards accomplishing this goal, pre-clinical models for these unique malignancies are of particular importance to design and test experimental therapeutic strategies prior to being introduced to patients due to their origination site and propensity to metastasize. Pre-clinical models offer several advantages for the study of pediatric sarcomas with unique benefits and shortcomings dependent on the type of model. This review addresses the types of pre-clinical models available for the study of pediatric solid tumors, with special attention to the bone sarcomas osteosarcoma and Ewing sarcoma.