Prognosis Of Rhabdomyosarcoma Research Articles

FOXO3 polymorphisms influence the risk and prognosis of rhabdomyosarcoma in children.

Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.

Fibrillar collagens promote cell proliferation, migration, and survival in various epithelial cancers and are generally associated with tumor aggressiveness. However, the impact of fibrillar collagens on soft tissue sarcoma behavior remains poorly understood. Unexpectedly, this study finds that fibrillar collagen‐related gene expression is associated with favorable patient prognosis in rhabdomyosarcoma. By developing and using collagen matrices with distinct stiffness and in vivo‐like microarchitectures, this study uncovers that the activation of DDR1 has pro‐apoptotic and of integrin β1 pro‐survival function, specifically in 3D rhabdomyosarcoma cell cultures. It demonstrates that rhabdomyosarcoma cell‐intrinsic or extrinsic matrix remodeling promotes cell survival. Mechanistically, the 3D‐specific collagen‐induced apoptosis results from a dual DDR1‐independent and a synergistic DDR1‐dependent TRPV4‐mediated response to mechanical confinement. Altogether, these results indicate that dense microfibrillar collagen‐rich microenvironments are detrimental to rhabdomyosarcoma cells through an apoptotic response orchestrated by the induction of DDR1 signaling and mechanical confinement. This mechanism helps to explain the preference of rhabdomyosarcoma cells to grow in and metastasize to low fibrillar collagen microenvironments such as the lung.

Racial and ethnic differences in presentation and clinical outcomes for pediatric rhabdomyosarcoma (RMS).

10017 Background: Race and ethnicity are recognized risk factors for many cancer types, including several pediatric cancers. Though racial and ethnic disparities in the presentation, treatment, and survival of certain cancers have been widely demonstrated, there is conflicting evidence about whether such disparities exist in RMS, the most common pediatric soft tissue sarcoma. Understanding the role of race and ethnicity in the presentation, treatment, and prognosis of RMS is important to promote improved survival in patients of all racial and ethnic groups. Methods: Patient, tumor, and treatment characteristics of patients enrolled on Children’s Oncology Group studies D9602, D9802, D9803, ARST0331, ARST0431, ARST0531, and ARST08P1 were compared across racial and ethnic groups using a chi-square test. Significant characteristics underwent pairwise analysis, comparing the Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) groups. Outcome analyses were performed using the Kaplan-Meier method and Wilcoxon signed-rank test. Results: Race and ethnicity incidence among the 2157 study patients were as follows: 8 (0.4%) American Indian or Alaska Native, 56 (2.6%) Asian, 271 (12.6%) Hispanic, 4 (0.2%) Native American or other Pacific Islander, 275 (12.8%) Non-Hispanic Black, 1335 (61.9%) Non-Hispanic White, and 208 (9.6%) unknown. Thirteen patient and tumor factors relating to presentation and treatment were evaluated for differences by race and ethnicity; the following five were significant: age, IRS group, tumor invasiveness, metastatic disease, and FOXO1 fusion partner. Pairwise comparison of NHB and NHW patients for these factors demonstrated that NHBs are more likely than NHWs to present at age 10 years or greater (p = 0.002) and that NHB patients are more likely to present with invasive tumors (p = 0.012). Incidence of metastatic disease at diagnosis was not significantly different between the groups (p = 0.202). No differences in treatment, including extent of surgical resection (p = 0.259) or use of radiation therapy (p = 0.920), were found. Neither event free survival nor overall survival were significantly different across the entire cohort (EFS p = 0.457, OS p = 0.159) or in subset analysis by risk group (low risk: EFS p = 0.856, OS p = 0.558; intermediate risk: EFS p = 0.907, OS p = 0.493; high risk: EFS p = 0.218, OS p = 0.397), by age (&lt; 1y: EFS p = 0.489, OS p = 0.546; 1-9y: EFS p = 0.417, OS p = 0.112; ≥10y: EFS p = 0.556, OS p = 0.609), in invasive tumors (EFS p = 0.704, OS p = 0.872), or in metastatic disease (EFS p = 0.270, OS p = 0.373). Conclusions: These data indicate that while differences in the presenting features of RMS exist between racial groups, with NHB patients exhibiting higher risk features, patients treated on these clinical trials did not experience differences in outcomes by racial group. This suggests NHB patients may experience a survival benefit from clinical trial enrollment.

Efficacy and prognostic analysis of 125I brathytherapy combined with chemotherapy for pediatric parameningeal rhabdomyosarcoma

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate (HR=38.40, 95%CI: 4.87-302.52, P=0.001). Within 3 months after 125I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

Isolation of NELL 1 Aptamers for Rhabdomyosarcoma Targeting.

NELL1 (Neural epidermal growth factor-like (EGFL)-like protein) is an important biomarker associated with tissue and bone development and regeneration. NELL1 upregulation has been linked with metastasis and negative prognosis in rhabdomyosarcoma (RMS). Furthermore, multiple recent studies have also shown the importance of NELL1 in inflammatory bowel disease and membranous nephropathy, amongst other diseases. In this study, several anti-NELL1 DNA aptamers were selected from a randomized ssDNA pool using a fluorescence-guided method and evaluated for their binding affinity and selectivity. Several other methods such as a metabolic assay and confocal microscopy were also applied for the evaluation of the selected aptamers. The top three candidates were evaluated further, and AptNCan3 was shown to have a binding affinity up to 959.2 nM. Selectivity was examined in the RH30 RMS cells that overexpressed NELL1. Both AptNCan2 and AptNCan3 could significantly suppress metabolic activity in RMS cells. AptNCan3 was found to locate on the cell membrane and also on intracellular vesicles, which matched the location of NELL1 shown by antibodies in previous research. These results indicate that the selected anti-NELL1 aptamer showed strong and highly specific binding to NELL1 and therefore has potential to be used for in vitro or in vivo studies and treatments.

Clinical group and modified TNM stage for rhabdomyosarcoma: A review from the Children's Oncology Group.

The Children's Oncology Group (COG) uses Clinical Group (CG) and modified Tumor Node Metastasis (TNM) stage to classify rhabdomyosarcoma (RMS). CG is based on surgicopathologic findings and is determined after the completion of initial surgical procedure(s) but prior to chemotherapy and/or radiation therapy. The modified TNM stage is based on clinical and radiographic findings and is assigned prior to any treatment. These systems have evolved over several decades. We review the history, evolution, and rationale behind the current CG and modified TNM classification systems used by COG for RMS. Data from the seven most recently completed and reported frontline COG trials (D9602, D9802, D9803, ARST0331, ARST0431, ARST0531, ARST08P1) were analyzed, and confirm that CG and modified TNM stage remain relevant and useful for predicting prognosis in RMS. We propose updates based on recent data and discuss factors warranting future study to further optimize these classification systems.

Abstract B15: Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute

Abstract Purpose: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We therefore performed a large-scale study through an international consortium to more accurately determine the incidence of driver mutations and their association with clinical outcome. Patients and Method: Formalin-fixed, paraffin-embedded material was collected from patients enrolled on Children’s Oncology Group trials and UK patients enrolled on MMT trials. Pathology was reviewed centrally and extracted DNA was subjected to targeted capture sequencing using a panel of 39 genes previously associated with RMS. Mutations, indels, deletions, gene amplifications, and copy number variation was called using analysis pipelines developed at the NCI. Results: DNA from six hundred and forty-one patients was suitable for analyses. A median of 1 variant call was found per tumor. Mutation of a RAS isoform was found in 29% of all fusion negative cases, mutation of a RAS pathway member was seen in greater than 50% of cases, and 24% had no putative driver mutation identified. BCOR (15%), NF1 (11%), and TP53 (12%) mutations were found at a higher incidence than previously reported. Interestingly, mutations in HRAS were notable in the infant population whereas those in NRAS were enriched in adolescents. Among infants &amp;lt; 1 year, 71% of cases harbored a mutation in HRAS or KRAS. In contrast, mutation of MYOD1 was associated with an older age and a head and neck primary site. Finally, 29% of the evaluated tumors harbored multiple driver mutations consistent with subclonal variation and tumor heterogeneity in fusion-negative RMS. Conclusion: This is the largest genomic characterization of clinically annotated RMS tumors to date and provides genetic features that refine risk stratification and can be incorporated into prospective trials. Citation Format: Jack Shern, Joanna Selfe, Rajesh Patidar, Young Song, Marielle Yohe, Jun Wei, Xinyu Wen, Erin Rudinski, Donald Barkauskas, David Hall, Corinne Linardic, Meriel Jenney, Julia Chisholm, Rebecca Brown, Anna Kelsey, Susanne Gatz, Stephen Skapek, Douglas Hawkins, Janet Shipley, Javed Khan. Genomic classification and prognosis in rhabdomyosarcoma: A report from the Children’s Oncology Group, the Institute of Cancer Research, and the National Cancer Institute [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B15.

Pediatric Tumors: Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a group of soft tissue sarcomas that share a common feature of primitive skeletal muscle differentiation. Three main subtypes have been characterized: embryonal, alveolar, and pleomorphic. Presentation and prognosis of RMS are highly variable, depending on anatomic location, subtype, and risk stratification. Currently, treatment centers on systemic control with cytotoxic chemotherapy and local control with surgery and/or therapeutic radiation. This review contains 3 figures, 10 tables and 50 references Key words: alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, pediatric soft tissue sarcoma, pleomorphic rhabdomyosarcoma, rhabdomyosarcona, t(2;13), t(1;13)

Pediatric Tumors: Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a group of soft tissue sarcomas that share a common feature of primitive skeletal muscle differentiation. Three main subtypes have been characterized: embryonal, alveolar, and pleomorphic. Presentation and prognosis of RMS are highly variable, depending on anatomic location, subtype, and risk stratification. Currently, treatment centers on systemic control with cytotoxic chemotherapy and local control with surgery and/or therapeutic radiation. This review contains 3 figures, 10 tables and 50 references Key words: alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, pediatric soft tissue sarcoma, pleomorphic rhabdomyosarcoma, rhabdomyosarcona, t(2;13), t(1;13)

小児外科的悪性腫瘍の予後追跡調査報告 : 昭和46年〜55年度登録症例について IV.横紋筋肉腫の予後と治療方法の関係

小児外科的悪性腫瘍の予後追跡調査報告 : 昭和46年〜55年度登録症例について IV.横紋筋肉腫の予後と治療方法の関係

Rhabdomyosarcoma

A malignant tumor of striated muscle origin, rhabdomyosarcoma (RMS) is a childhood tumor that has benefited from nearly 30 years of multimodality therapy, culminating in a >70% overall 5-year survival. Prognosis for RMS is dependent on primary tumor site, age, completeness of resection, presence and number of metastatic sites, histology, and biology of the tumor cells. Multimodality treatment is based on risk stratification according to pre-treatment stage, postoperative group, histology, and site. Unique to RMS is the concept of postoperative clinical grouping that assesses the completeness of disease resection and takes into account lymph node evaluation at both the regional and metastatic basins. At all sites, if complete operative resection of disease is accomplished, including microscopic disease, survival is improved. Therefore, the surgeon plays a vital role in determining risk stratification for treatment, local control of the primary tumor and overall outcome for the patient with RMS.

Expressions of HIF-1α and VEGF in rhabdomyosarcoma and their clinical significance

Objective: To investigate the expressions of HIF-1α (hypoxia inducible factor-1α) and VEGF (vascular endothelial growth factor) in rhabdomyosarcoma and their clinical significance. Methods: The expressions of HIF-1α and VEGF preteins in 70 cases of rhabdomyosarcoma were detected by immunohistochemistry, and the correlations of the expressions of HIF-1α and VEGF with the clinicopathological characteristics and the prognosis were analyzed. Results: The positive-expression rates of HIF-1α and VEGF in rhabdomyosarcoma tissues were 75.7% (53/70) and 72.9% (51/70), respectively. HIF-1α expression was positively correlated to VEGF expression (r = 0.554, P = 0.000). HIF-1α expression was significantly associated with the factors of gender (P = 0.035), tumor size (P = 0.016) and clinical staging (P = 0.008), but it was not associated with the age (P = 0.555), pathological type (P = 0.625) and lymph node metastasis (P = 0.750). The three-year overall survival rates of HIF-1α-negative patients and HIF-1α-positive patients were 54.5% and 38.0%, respectively (P = 0.045). VEGF expression was significantly associated with clinical stage (P = 0.026), but it was not associated with the age (P = 0.478), gender (P = 0.944), tumor size (P = 0.535), pathological type (P = 0.399) and lymph node metastasis (P = 0.356). The three-year overall survival rates of VEGF-negative patients and VEGF-positive patients were 68.1% and 31.1% (P = 0.011). COX regression model showed that the factors of VEGF expression (P = 0.005), clinical staging (P = 0.004) and tumor size (P = 0.000) were independent predictors of poor prognosis of rhabdomyosarcoma. HIF-1α could not be considered as an independent prognostic factor of rhabdomyosarcoma (P = 0.845). Conclusion: The overexpression of HIF-1α and VEGF in rhabdomyosarcoma is related to clinical staging. HIF-1α expression is associated with VEGF expression, and VEGF is an independent predictor of poor prognosis of rhabdomyosarcoma. DOI:10.3781/j.issn.1000-7431.2012.08.012

Identification of a novel synthetic lethality of combined inhibition of hedgehog and PI3K signaling in rhabdomyosarcoma.

We previously reported that aberrant HH pathway activation confers a poor prognosis in rhabdomyosarcoma (RMS). Searching for new treatment strategies we therefore targeted HH signaling. Here, we identify a novel synthetic lethality of concomitant inhibition of HH and PI3K/AKT/mTOR pathways in RMS by GLI1/2 inhibitor GANT61 and PI3K/mTOR inhibitor PI103. Synergistic drug interaction is confirmed by calculation of combination index (CI < 0.2). Similarly, genetic silencing of GLI1/2 significantly increases PI103-induced apoptosis. GANT61 and PI103 also synergize to induce apoptosis in cultured primary RMS cells emphasizing the clinical relevance of this combination. Importantly, GANT61/PI103 cotreatment suppresses clonogenic survival, three-dimensional sphere formation and tumor growth in an in vivo model of RMS. Mechanistic studies reveal that GANT61 and PI103 cooperate to trigger caspase-dependent apoptosis via the mitochondrial pathway, as demonstrated by several lines of evidence. First, GANT61/PI103 cotreatment increases mRNA and protein expression of NOXA and BMF, which is required for apoptosis, since knockdown of NOXA or BMF significantly reduces GANT61/PI103-induced apoptosis. Second, GANT61/PI103 cotreatment triggers BAK/BAX activation, which contributes to GANT61/PI103-mediated apoptosis, since knockdown of BAK provides protection. Third, ectopic expression of BCL-2 or non-degradable phospho-mutant MCL-1 significantly rescue GANT61/PI103-triggered apoptosis. Fourth, GANT61/PI103 cotreatment initiate activation of the caspase cascade via apoptosome-mediated cleavage of the initiator caspase-9, as indicated by changes in the cleavage pattern of caspases (e.g. accumulation of the caspase-9 p35 cleavage fragment) upon addition of the caspase inhibitor zVAD.fmk. Thus, combined GLI1/2 and PI3K/mTOR inhibition represents a promising novel approach for synergistic apoptosis induction and tumor growth reduction with implications for new treatment strategies in RMS.

Rhabdomyosarcoma: Advances in Molecular and Cellular Biology.

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

Rhabdomyosarcoma in middle to old-aged patients: analysis of clinicopathological features and prognosis in 76 cases

Albeit rare, rhabdomyosarcoma (RMS) may occur in middle to old-aged adults. The purpose of this study was to investigate the clinicopathological characteristics and prognosis of RMS in patients ≥ 40 years of age. The clinical, pathological and immunohistochemical profiles of the 76 cases were reviewed, and the outcomes were analyzed. There were 46 males and 30 females with a median age of 55 years. Sixty cases occurred in somatic soft tissues, including extremities (n = 25), head and neck (n = 19) and trunk (n = 16). Sixteen developed in the internal organs with predilection for the urogenital tract. Histologically, 38 cases (50.0%) were of embryonal RMS (ERMS) subtype, 29 cases (38.2%) of pleomorphic RMS (PRMS), 7 cases (9.2%) of poorly-differentiated RMS (PdRMS), and 2 cases (2.6%) of alveolar RMS (ARMS). Immunohistiochemically, the tumor cells showed diffuse staining of desmin (68/68, 100%), with a variable expression of myogenin (30/43, 69.8%), MyoD1 (33/51, 64.7%) and MSA (29/40, 72.5%). The therapy data available in 54 cases showed that three inoperable cases were treated with chemotherapy and radiotherapy, 51 cases underwent local excision, including 10 cases with chemotherapy, 9 cases with radiotherapy, 8 cases with chemotherapy and radiotherapy after surgery, and the remaining 24 cases were not administrered with postoperative adjuvant therapy. The follow-up data available in 54 cases showed that 22 patients were alive with unresectable or recurrent/disease and 32 patients were alive with no evidence of disease. The median disease-free and overall survivals were 6.0 months and 7.0 months, respectively. Twenty-seven patients exhibited progression of disease with recurrence in 8 cases and metastasis in 19 cases. The median interval to progression was 6.0 months. The most common subtypes of RMS in middle to old aged patients are ERMS and PRMS. In general, Rhabdomyosarcomas of middle to old aged patients shows a highly aggressive behavior. Patients may benefit from multi-disciplinary therapy.

Update on rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a malignant childhood tumor of mesenchymal origin that currently has a greater than 70% overall 5-year survival. Multimodality treatment is determined by risk stratification according to pretreatment stage, postoperative group, histology, and site of the primary tumor. Pretreatment staging is dependent on primary tumor site, size, regional lymph node status, and presence of metastases. Unique to RMS is the concept of postoperative clinical grouping that assesses the completeness of disease resection and takes into account lymph node evaluation. At all tumor sites, the clinical grouping, and therefore completeness of resection, is an independent predictor of outcome. Overall, the prognosis for RMS is dependent on primary tumor site, patient age, completeness of resection, extent of disease, including the presence and number of metastatic sites and histology and biology of the tumor cells. Therefore, the surgeon plays a vital role in RMS by contributing to risk stratification for treatment, local control of the primary tumor, and outcome. The current state-of-the-art treatment is determined by treatment protocols developed by the Soft Tissue Sarcoma Committee of the children's Oncology Group.

Tumeurs malignes indifférenciées à cellules rondes des cavités naso-sinusiennes et du nasopharynx

Undifferentiated malignant round cell tumors of the sinonasal tract and nasopharynx comprise of aggressive malignant neoplasms with overlapping morphologic features, which yet are very different and can be identified as carcinoma, lymphoma, sarcoma, melanoma or olfactory neuroblastoma. Differentiating these tumors is important because their treatment and prognosis are quite different. Because of the limited initial biopsy tissue materials, major differential diagnostic difficulties may arise. The use of a panel of immunohistochemical markers and the identification, in some cases, of specific chromosomal translocations are most often required. We describe clinical, morphological, immunohistochemical and molecular features as well as therapeutic management and prognosis of rhabdomyosarcoma (RMS), Ewing sarcoma/primitive neuroectodermic tumor (EWS/PNET), nonkeratinizing nasopharyngeal carcinoma, undifferentiated subtype (UCNT), olfactory neuroblastoma (ONB), small cell carcinoma, neuroendocrine type (SCCNET), sinonasal undifferentiated carcinoma (SNUC) and mucosal melanoma. Mesenchymal chondrosarcoma, small round cell synovialosarcoma, lymphomas and plasmocytoma are not introduced. The most important features of diagnosis will be summarized in two tables.

Les tumeurs mésenchymateuses du nouveau-né

Soft tissue tumors account for approximately 25% of neonatal tumors and are most often benign (more than 2/3 of cases). Vascular tumors are the most frequent benign tumors and infantile hemangioma accounts for 32% of these tumors, affecting 1 out of 200 children at birth. Kaposiform hemangioendothelioma (KH) is a rare vascular tumor with locally aggressive behavior. More than 50% of KH are associated with the Kasabach-Merritt phenomenon, a condition characterized by thrombocytopenia and consumptive coagulopathy. Malignant soft tissue tumors are, after neuroblastoma, the second cause of cancer in neonates. Infantile fibrosarcoma (IF) is a rare tumor that most often affects the extremities of children aged 4 years or younger. A recurrent t(12;15) (p13;q25) rearrangement fusing the ETV6 gene with the NTRK3 neurotrophin-3 receptor gene has been identified in IF. Complete conservative surgical resection is usually curative. Chemotherapy is indicated when initial surgical removal cannot be accomplished without unacceptable morbidity. Prognosis of IF is excellent, with reported overall survival rates ranging from 80 to 100%. Neonatal rhabdomyosarcoma (RMS) is a rare tumor (0.5-1% of RMS). The primary tumor predominantly involves the limbs and the genitourinary tract. Treatment is based on age-adapted chemotherapy and surgery. Prognosis of RMS in children less than 1 year old appears to be comparable with that of older children.

Initial Response to Treatment was Highly Associated with the Prognosis of Childhood Rhabdomyosarcoma: A Retrospective Analysis of a Single Center Experience in Korea

Following the introduction of a multimodal approach to diagnosis and treatment, the prognosis of rhabdomyosarcoma (RMS) has markedly improved over the last three decades. However, there are few data on treatment outcomes in Korean patients. We performed a retrospective analysis of 77 patients with RMS diagnosed and treated at Seoul National University Children's Hospital between 1986 and 2005. The overall 5-year survival and event-free survival rates for all patients were 77% and 59%, respectively. The Intergroup Rhabdomyosarcoma Study clinical grouping and initial response to treatment (20-week response) were important prognostic factors. The outcome of childhood RMS was closely associated with the initial staging and the initial response to treatment. Modulating therapies according to initial responses and risk factors is critical, and new treatment strategies for high-risk patients are needed.

Pediatric surgical oncology: Management of rhabdomyosarcoma

A malignant tumor of striated muscle origin, Rhabdomyosarcoma (RMS) is a childhood tumor that has benefited from 30 years of multimodality therapeutic trials culminating in a greater than 70% overall current 5-year survival. Prognosis for RMS is dependent on anatomic primary tumor site, age, completeness of resection, presence and number of metastatic sites, histology and biology of the tumor cells. Multimodality treatment is based on risk stratification according to pretreatment stage, postoperative group, histology and site. Therefore, pretreatment staging is vital for assessment and is dependent on primary tumor site, size, regional lymph node status, and presence of metastases. Unique to RMS is the concept of postoperative clinical grouping that assesses the completeness of disease resection and takes into account lymph node evaluation both at the regional and metastatic basins. At all sites, if operative resection of all disease is accomplished, including microscopic disease, survival is improved. Therefore, the surgeon plays a vital role in determining risk stratification for treatment and local control of the primary tumor for RMS.