Childhood Soft Tissue Sarcomas
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Childhood soft tissue sarcomas account for approximately 10% of all childhood cancers. About half of all childhood soft tissue sarcomas are rhabdomyosarcoma, which arises from skeletal muscle, these are most common between the ages of 2 and 6. The other soft tissue sarcomas of childhood include a wide range of different histologies including fibrosarcoma, leiomyosarcoma, liposarcoma, schwannoma, soft tissue Ewing's / peripheral neuroectodermal tumours, synovial sarcoma and many other types. These non-rhabdo sarcomas are more common in adults, but these tumours usually behave quite differently in children compared to the same tumours in adults

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Rhabdomyosarcoma

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Zin A, Bertorelle R, Dall'Igna P, et al.
Epithelioid rhabdomyosarcoma: a clinicopathologic and molecular study.
Am J Surg Pathol. 2014; 38(2):273-8 [PubMed] Related Publications
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and is mostly represented by the embryonal (ERMS) and alveolar (ARMS) histotypes. Whereas ERMS shows variable genetic alterations including TP53, RB1, and RAS mutations, ARMS carries a gene fusion between PAX3 or PAX7 and FOXO1. Epithelioid RMS is a morphologic variant of RMS recently described in adults. Five cases of epithelioid RMS were identified after histologic review of 85 cases of ARMS enrolled in Italian therapeutic protocols. Immunostaining analyses (muscle-specific actin, desmin, myogenin, AP-2β, EMA, cytokeratins, INI-1) and reverse transcription polymerase chain reaction assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. In 4 cases DNA sequencing of TP53 was performed; and RB1 allelic imbalance and homozygous deletion were analyzed by quantitative real-time polymerase chain reaction. Histologically, epithelioid RMS displayed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; necrosis was evident in 4, often with a geographic pattern. Immunostainings for INI, desmin, myogenin (scattered cells in 4, diffuse in 1) were positive in all; EMA and MNF116 were positive in 2; AP-2β was negative. PAX3/7-FOXO1 transcripts were absent. In all cases RB1 was wild type, and a TP53 mutation at R273H codon was found in 1. All patients are in complete remission, with a median follow-up of 6 years. Epithelioid RMS may occur in children and is probably related to ERMS, as suggested by lack of fusion transcripts, weak staining for myogenin, negative AP-2β, evidence of TP53 mutation (although only in 1 case), and a favorable clinical course.

Related: Rhabdomyosarcoma


Chen X, Stewart E, Shelat AA, et al.
Targeting oxidative stress in embryonal rhabdomyosarcoma.
Cancer Cell. 2013; 24(6):710-24 [PubMed] Article available free on PMC after 09/12/2014 Related Publications
Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.


Senerchia AA, Ribeiro KB, Rodriguez-Galindo C
Trends in incidence of primary cutaneous malignancies in children, adolescents, and young adults: a population-based study.
Pediatr Blood Cancer. 2014; 61(2):211-6 [PubMed] Related Publications
BACKGROUND: Skin cancer incidence among young adults is rising; however, the epidemiological characteristics of primary cutaneous lymphomas and cutaneous soft tissue sarcomas (CSTS) in individuals <30 years old has not been investigated. We analyzed the incidence and time-trends of primary cutaneous malignancies in children and adolescents/young adults (AYA).
PROCEDURE: SEER-17 and -13 data were used to assess the descriptive epidemiology and time-trends in incidence of primary cutaneous malignancies in children and AYA. SEERStat and Joinpoint softwares were utilized to estimate annual percent changes (APC) in incidence.
RESULTS: In total, 7,814 cases (ASR = 25.66/1,000,000 habitants) of primary skin cancers in <30 years old were diagnosed in 2000-2008. Females had a higher incidence of melanoma (risk ratio (RR) = 1.95; P < 0.001) and a lower risk of developing CSTS (RR = 0.64, P < 0.001). Compared to whites, blacks have a lower incidence of melanoma (RR = 0.03, P < 0.001), and higher risk of CSTS (RR = 2.28, P < 0.001). Melanoma increased in females over a 15-year period (1992-2006) (APC = 2.5, 95%CI = 1.8; 3.2), and the incidence of cutaneous T-cell lymphomas increased over the period 1992-2008 (APC = 9.5, 95% CI = 6.7; 12.4). CSTS incidence decreased among males over the period 1992-1999 (APC = -21.4, 95% CI -27.2; -15.1), particularly due to a decrease in Kaposi sarcoma incidence (AAPC 1992-2008 = -13.6, 95% CI = -22.4;-3.8), although with a notable racial disparity (whites, AAPC = -15.2, 95% CI = -23.2;-6.4; blacks, AAPC = -10.6, 95% CI = -13.2;-7.9).
CONCLUSIONS: Non-melanoma skin cancer is very rare in children and AYA. We have shown variation in time-trends in incidence as well as in incidence patterns by race, sex, age, and histologic type, highlighting the importance of descriptive epidemiology to better understand the characteristics of these malignancies.

Related: Haematological Malignancies & Realted Disorders Cutaneous T-cell lymphoma Melanoma Skin Cancer USA


Thacker MM
Malignant soft tissue tumors in children.
Orthop Clin North Am. 2013; 44(4):657-67 [PubMed] Related Publications
Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases.

Related: Cancer Cytogenetics


Zhang WL, Zhang Y, Huang DS, et al.
Clinical character of pediatric head and neck rhabdomysarcomas: a 7-year retrospective study.
Asian Pac J Cancer Prev. 2013; 14(7):4089-93 [PubMed] Related Publications
OBJECTIVE: The rhabdomysarcoma (RMS) is most common soft tissue carcinoma in children, mostly found in the head and neck with high degree of malignancy. The current study aimed to summarize clinical data and evaluate treatment outcome of cases in a single hospital.
METHODS: Forty-one (24 male, 17 female) children with newly diagnosed RMS in Beijing Tong Ren Hospital were enrolled between November, 2004 and May, 2011. The. Students' t and Chi tests were then performed on retrospectively reviewed clinical data, followed by survival analysis based on the Kaplan Meier method using SPSS 17.0 software.
RESULTS: Of all cases, 32 were treated by common chemotherapy, and 3 cases with stage III RMS received high-dose chemotherapy and auto-peripheral blood stem cell transplantation (APBSCT). Side-effects in the former were: I grade for 62.5% (20/32), II grade for 28.1% (9/32), III grade account for 9.275% (3/32). Side-effects of 3 cases with APBSCT: 2 were I grade, 1 was III grade. The median follow-up time of 41 RMS cases was 41 months. Four cases were lost to follow-up, 7 cases recurred, and 5 cases died of cerebral metastasis, witha total survival rate was 86.5% (32/37). CR rate was 67.6% (25/37), PR was 18.9% (7/37).
CONCLUSION: Multidiscipline treatment including chemotherapy, radiotherapy, surgery and auto-PBSCT is highly recommended for pediatric patients with head and neck RMS.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology Rhabdomyosarcoma


Schoot RA, McHugh K, van Rijn RR, et al.
Response assessment in pediatric rhabdomyosarcoma: can response evaluation criteria in solid tumors replace three-dimensional volume assessments?
Radiology. 2013; 269(3):870-8 [PubMed] Related Publications
PURPOSE: To investigate (a) interobserver variability for three-dimensional (3D) (based on European Pediatric Soft-Tissue Sarcoma Study Group [EpSSG] guidelines) and one-dimensional (1D) (based on Response Evaluation Criteria in Solid Tumors [RECIST]) response assessments, (b) intermethod variability between EpSSG guidelines and RECIST, and (c) clinically relevant consequences of interobserver and intermethod variability in pediatric patients with rhabdomyosarcoma.
MATERIALS AND METHODS: The study was approved by the Academic Medical Center Ethics Committee and the Great Ormond Street Hospital Ethics Committee; both committees waived the requirement for informed consent because of the retrospective nature of the study. Data were analyzed from 124 consecutive male and female children and young adults (age range, 1-18 years) with rhabdomyosarcoma at two institutions (1999-2009) with relevant imaging studies. Tumors were measured by two radiologists (1D and 3D measurements) at diagnosis and after induction chemotherapy. Interobserver variability was analyzed by using three different tests, and the intermethod variation was calculated.
RESULTS: Sixty-four eligible patients were included (median age, 4.6 years). Agreement between observers for EpSSG guidelines and RECIST was moderate (κ = 0.565 and 0.592, respectively); interobserver variation led to different potential treatment decisions in nine (14%) and 11 (17%) of the 64 patients, respectively. Comparison of EpSSG guidelines and RECIST resulted in 13 discrepant response classifications (20%), which were equally distributed (under- and overestimation of response) and led to consequences for treatment choice in five patients (8%).
CONCLUSION: EpSSG guidelines and RECIST are not interchangeable; neither technique demonstrated superiority in this study. These findings should be taken into account in future study protocol design. Online supplemental material is available for this article.

Related: Rhabdomyosarcoma


Krishnan J, Hathiramani V, Hastak M, Redkar RG
Myxoid lipoblastoma.
Indian Pediatr. 2013; 50(6):603-5 [PubMed] Related Publications
A rapidly growing soft tissue mass in the axilla of an infant raises the suspicion of a lipoblastoma or a liposarcoma. Excisional/incisional biopsy is vital in confirming the diagnosis and hence avoiding aggressive extirpation. This case report highlights the role of histopathology and immunohistochemistry as the gold standard in differentiating a lipoblastoma from a liposarcoma. In some cases where the histopathology is inconclusive, genetic rearrangement of the PLAG1 (pleomorphic adenoma gene 1) oncogene on chromosome 8q12 helps in confirming the diagnosis of lipoblastoma.


Guo Y, Xie D, Yan J, et al.
Primary pulmonary rhabdomyosarcoma with brain metastases in a child: a case report with medico-legal implications.
J Forensic Leg Med. 2013; 20(6):720-3 [PubMed] Related Publications
Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma that mainly affects children. RMS in childhood commonly occurs in the head and neck, followed by the genitourinary tract. Primary pulmonary rhabdomyosarcoma (PPR) is extremely rare. We report a 31-month-old girl who had PPR with brain metastasis. The girl with wheezing and cough of 3 weeks and vomiting of 1 day was referred to a county hospital. At 9:00 a.m., a chest X-ray showed an abnormal shadow on a chest radiogram. Four hours later, in the process of computed tomography (CT) scan her condition deteriorated dramatically, while resuscitation efforts were unsuccessful. CT showed a solid mass in the right middle lung lobe. Subsequent autopsy revealed a large tumour located in the right middle lung lobe. Surprisingly, a mass of haematoma appearance was found in the left occipital lobe. Histological and immunohistochemical investigations of the masses established the diagnosis of PPR with brain metastasis. Herniation of brain, caused by the brain metastasis, was ascertained as the cause of death. The morphological and pathological findings are presented; the difficulty to diagnose PPR and the medico-legal implications are discussed.

Related: Lung Cancer Rhabdomyosarcoma


Fanzani A, Monti E, Donato R, Sorci G
Muscular dystrophies share pathogenetic mechanisms with muscle sarcomas.
Trends Mol Med. 2013; 19(9):546-54 [PubMed] Related Publications
Several lines of recent evidence have opened a new debate on the mechanisms underlying the genesis of rhabdomyosarcoma, a pediatric soft tissue tumor with a widespread expression of muscle-specific markers. In particular, it is increasingly evident that the loss of skeletal muscle integrity observed in some mouse models of muscular dystrophy can favor rhabdomyosarcoma formation. This is especially true in old age. Here, we review these experimental findings and focus on the main molecular and cellular events that can dictate the tumorigenic process in dystrophic muscle, such as the loss of structural or regulatory proteins with tumor suppressor activity, the impaired DNA damage response due to oxidative stress, the chronic inflammation and the conflicting signals arising within the degenerated muscle niche.

Related: Rhabdomyosarcoma


Tarik E, Lamiae R, Abdelouahed A, et al.
Unusual case of congenital/infantile fibrosarcoma in a new born.
Afr J Paediatr Surg. 2013 Apr-Jun; 10(2):185-7 [PubMed] Related Publications
Congenital infantile fibrosarcoma (CIFS) is a rare mesenchymal tumor that is primarily developed in the soft tissue of distal extremities and occasionally in unusual locations such as the lung and retroperitoneum. It occurs mainly in children below the age of 5 years. About 200 cases have been reported in the literature so far, very few of them in new-borns. The prognosis of this tumor is relatively good compared to adult forms. We report an unusual case of CIFS occurring in new-born mimicking an hemangioma and causing hemorrhage in the neonatal period. The tumor is located in the left arm and axilla and associated with a hand malformation. A shoulder amputation is performed after chemotherapy failure. The infant is now two-years old with no recurrence.


Glade Bender JL, Lee A, Reid JM, et al.
Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children's oncology group phase I consortium report.
J Clin Oncol. 2013; 31(24):3034-43 [PubMed] Article available free on PMC after 20/08/2014 Related Publications
PURPOSE: Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs progression-free survival in adults with soft tissue sarcoma (STS). A phase I pharmacokinetic and pharmacodynamic study of two formulations of pazopanib was performed in children with STS or other refractory solid tumors.
PATIENTS AND METHODS: Pazopanib (tablet formulation) was administered once daily in 28-day cycles at four dose levels (275 to 600 mg/m(2)) using the rolling-six design. Dose determination for a powder suspension was initiated at 50% of the maximum-tolerated dose (MTD) for the intact tablet. Ten patients with STS underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning at baseline and 15 ± 2 days after initiation of pazopanib at the tablet MTD.
RESULTS: Fifty-three patients were enrolled; 51 were eligible (26 males; median age, 12.9 years; range, 3.8 to 23.9 years). Hematologic and nonhematologic toxicities were generally mild, with dose-limiting lipase, amylase, and ALT elevation, proteinuria, and hypertension. One patient with occult brain metastasis had grade 4 intracranial hemorrhage. The MTD was 450 mg/m(2) for tablet and 160 mg/m(2) for suspension. Steady-state trough concentrations were reached by day 15 and did not seem to be dose dependent. One patient each with hepatoblastoma or desmoplastic small round cell tumor achieved a partial response; eight patients had stable disease for ≥ six cycles, seven of whom had sarcoma. All patients with evaluable DCE-MRI (n = 8) experienced decreases in tumor blood volume and permeability (P < .01). Placental growth factor increased, whereas endoglin and soluble vascular endothelial growth factor receptor-2 decreased (P < .01; n = 41).
CONCLUSION: Pazopanib is well tolerated in children, with evidence of antiangiogenic effect and potential clinical benefit in pediatric sarcoma.

Related: Angiogenesis Inhibitors Cancer Prevention and Risk Reduction Children's Cancer Web: Home Page Pazopanib (Votrient)


Orbach D, Brennan B, Casanova M, et al.
Paediatric and adolescent alveolar soft part sarcoma: A joint series from European cooperative groups.
Pediatr Blood Cancer. 2013; 60(11):1826-32 [PubMed] Related Publications
BACKGROUND: Alveolar soft part sarcomas (ASPS) are generally chemo- and radio-resistant mesenchymal tumours, with no standardized treatment guidelines. We describe the clinical behaviour of paediatric ASPS and compare these features to previously reported adult series.
PATIENTS AND METHODS: The clinical data of 51 children and adolescents with ASPS, prospectively enrolled in or treated according to seven European Paediatric trials were analysed.
RESULTS: Median age was 13 years [range: 2-21]. Primary sites included mostly limbs (63%). IRS post-surgical staging was: IRS-I (complete resection) 35%, II (microscopic residual disease) 20%, III (gross residual disease) 18% and IV (metastases) 27%. Only 3 of the 18 evaluable patients (17%) obtained a response to conventional chemotherapy. After a median follow-up of 126 months (range: 9-240), 14/18 patients with IRS-I tumour, 10/10 IRS-II, 7/9 IRS-III and 2/14 IRS-IV were alive in remission. Sunitinib treatment achieved two very good partial responses in four patients. Ten-year overall survival (OS) and event free survival (EFS) was 78.0 ± 7% and 62.8 ± 7% respectively. Stage IV, size >5 cm and T2 tumours had a poorer outcome, but only IRS staging was an independent prognostic factor.
CONCLUSIONS: ASPS is a very rare tumour frequently arising in adolescents and in the extremities, and chemo resistant. Local surgical control is critical. ASPS is a poorly chemo sensitive tumour. For IRS-III/IV tumours, delayed radical local therapies including surgery are essential. Metastatic patients had a poor prognosis but targeted therapies showed promising results.


Keller C, Guttridge DC
Mechanisms of impaired differentiation in rhabdomyosarcoma.
FEBS J. 2013; 280(17):4323-34 [PubMed] Related Publications
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, with presumed skeletal muscle origins, because of its myogenic phenotype. RMS is composed of two main subtypes, embryonal RMS (eRMS) and alveolar RMS (aRMS). Whereas eRMS histologically resembles embryonic skeletal muscle, the aRMS subtype is more aggressive and has a poorer prognosis. In addition, whereas the genetic profile of eRMS is not well established, aRMS is commonly associated with distinct chromosome translocations that fuse domains of the transcription factors Pax3 and Pax7 to the forkhead family member FOXO1A. Both eRMS and aRMS tumor cells express myogenic markers such as MyoD, but their ability to complete differentiation is impaired. How this impairment occurs is the subject of this review, which will focus on several themes, including signaling pathways that converge on Pax-forkhead gene targets, alterations in MyoD function, epigenetic modifications of myogenic promoters, and microRNAs whose expression patterns in RMS alter key regulatory circuits to help maintain tumor cells in an opportunistically less differentiated state.

Related: Rhabdomyosarcoma


Novák J, Vinklárek J, Bienertová-Vašků J, Slabý O
MicroRNAs involved in skeletal muscle development and their roles in rhabdomyosarcoma pathogenesis.
Pediatr Blood Cancer. 2013; 60(11):1739-46 [PubMed] Related Publications
MicroRNAs (miRs) are small non-coding RNAs known to fulfill various functions in tissue development, function, and pathogenesis of various diseases, including cancer. Rhabdomyosarcoma (RMS) represents the most common soft tissue tumor in the pediatric population. miRs have been shown to play important roles in RMS pathogenesis and some of the studies suggest their potential as diagnostic, prognostic, and even therapeutic tools facilitating better management of this disease. This review summarizes current information about the role of miRs in the development of normal skeletal muscle and their deregulation in RMS.

Related: Rhabdomyosarcoma


Goswamy J, Aggarwal R, Bruce IA, Rothera MP
Kasabach-Merritt syndrome in a child with upper airway compromise and spontaneous periorbital bruising.
Ear Nose Throat J. 2013; 92(6):E16 [PubMed] Related Publications
A hemangioma that rapidly increases in size has the potential to trap platelets and cause a consumptive coagulopathy. We describe the case of an 18-week-old boy who was brought to a local emergency department with ecchymosis on his nasal bridge and medial epicanthi, as well as a subconjunctival hemorrhage. He was noted to be anemic and thrombocytopenic. Packed red blood cells and platelets were transfused. However, despite hematologic correction, the ecchymosis and petechiae worsened, and a mass became evident in the right posterior triangle of the patient's neck. Computed tomography demonstrated a lobular soft-tissue-density mass in the right posterior triangle that extended to the level of the skull base. Histologic analysis of a biopsy specimen revealed that the lesion was a giant kaposiform hemangioma. The patient was diagnosed with Kasabach-Merritt syndrome, and prednisolone was commenced as a first-line treatment. However, the mass continued to grow, resulting in inspiratory stridor. Magnetic resonance imaging revealed encroachment into the thecal sac and compression of the spinal cord. The lesion was embolized, and vincristine therapy was commenced. Following a second embolization, the size of the lesion decreased and no further blood products were required. The hemangioma was deemed to be unresectable. The successful treatment in this case was dependent on the maintenance of hemostasis, the initial medical treatment with a corticosteroid, repeat embolization, and longer-term control with vincristine.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology Kaposi Sarcoma Vincristine


Dang ND, Dang PT, Samuelian J, Paulino AC
Lymph node management in patients with paratesticular rhabdomyosarcoma: a population-based analysis.
Cancer. 2013; 119(17):3228-33 [PubMed] Related Publications
BACKGROUND: Paratesticular rhabdomyosarcoma (PTRMS) is the most common primary solid tumor arising from the mesenchymal tissue of the testis. Traditionally, retroperitoneal lymph node dissection is not recommended for children aged <10 years because of the morbidity of the procedure and low risk of retroperitoneal lymph node involvement. In the current study, the authors analyzed the patient and tumor characteristics of PTRMS as well as survival outcomes associated with lymph node dissection status.
METHODS: A total of 255 cases of PTRMS were identified from the patient data reported by the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973 through 2009.
RESULTS: Among 173 patients aged ≥ 10 years, lymph node dissection was found to improve the 5-year overall survival (OS) rate from 64% to 86% (P  <  0.01). Conversely, patients aged <10 years fared extremely well regardless of lymph node dissection status; the 5-year OS rate was 100% and 97%, respectively, for patients who did versus those who did not undergo lymph node dissection (P  = .37). The yield of positive lymph nodes was approximately ≥  20% when <  11 lymph nodes were removed. The incidence of lymph node involvement was also higher in older patients compared with younger patients (40% vs 8%). Radiotherapy improved the OS rate in patients with lymph node involvement (5-year OS rate: 90% with vs 36% without radiation; P < .0001).
CONCLUSIONS: Lymph node dissection is recommended in patients aged ≥10 years. Radiotherapy is beneficial in patients with lymph node-positive disease.

Related: Rhabdomyosarcoma Testicular Cancer


Warren M, Weindel M, Ringrose J, et al.
Integrated multimodal genetic testing of Ewing sarcoma--a single-institution experience.
Hum Pathol. 2013; 44(10):2010-9 [PubMed] Related Publications
Ewing sarcoma (ES) is an aggressive malignant small round cell tumor that arises in bone or soft tissue of adolescents and young adults. A characteristic molecular finding in ES is EWSR1 gene fusion with ETS (erythroblast transformation-specific) family genes including FLI1 (~90%) and ERG (>5%). Here we report our experience using integrated clinicopathologic, cytogenetic, fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of 32 pediatric patients with ES diagnosed in a single institution between 2005 and 2011. Diagnostic EWSR1 rearrangements were detected in 30 (93.8%) of 32 patients. Cytogenetics detected t(11;22) (n = 14) and t(21;22) (n = 1) in 15 (46.9%) patients. FISH detected EWSR1 rearrangements in 27 (96.4%) of 28 patients tested. RT-PCR was positive in 27 (84.4%) of 32 patients, including 24 EWSR1-FLI1 and 3 EWSR1-ERG. RT-PCR defined breakpoints and fusion partners in 7 cases with EWSR1 rearrangements detected by FISH. Sanger sequencing further delineated breakpoints in 21 (77.8%) of 27 RT-PCR positive cases. In summary, conventional cytogenetic analysis provided a global view but had a lower detection rate and longer turnaround time than other methods. FISH is a rapid method and theoretically can detect all EWSR1 rearrangements, but it cannot identify all partners and is not completely specific for ES. RT-PCR and sequencing are more sensitive and useful in identifying fusion partners and refining breakpoints; however, these methods can be compromised by poor RNA preservation and primer design. In conclusion, an integrated approach that uses all methods capable of detecting EWSR1 rearrangements has value in the workup of suspected cases of ES.

Related: Bone Cancers Chromosome 11 Chromosome 22 FISH ERG gene EWSR1 gene


Qureshi SS, Kembhavi S, Vora T, et al.
Prognostic factors in primary nonmetastatic Ewing sarcoma of the rib in children and young adults.
J Pediatr Surg. 2013; 48(4):764-70 [PubMed] Related Publications
BACKGROUND: The rarity of Ewing sarcoma of rib has resulted in paucity of data, particularly on the prognostic factors and pattern of relapses. We analyzed the recurrences in patients with primary nonmetastatic Ewing sarcoma of the rib and examined prognostic factors of poor outcome.
METHODS: From January 2004 to January 2011, 37 patients were treated. After induction chemotherapy, complete (from costal cartilage to vertebra) or partial excision of involved rib with or without adjacent ribs was performed. Postoperative radiotherapy was administered for positive margins, poor response to chemotherapy, and large primary tumors with significant soft tissue component at presentation.
RESULTS: Disease relapsed in 16 patients: at the local site (n = 5), both local and distant (n = 2), and distant site only (n = 9). The projected 5-year cause-specific, relapse-free survival and local control were 50%, 44%, and 72%. Poor response to chemotherapy (>5% residual tumor) and resection of adjacent lung parenchyma (a surrogate for tumor extension) were adverse prognostic factors for relapse-free survival in multivariate analysis.
CONCLUSION: Relapses occurred more often at distant sites and had a poor outcome. In this study, poor histologic response to chemotherapy (P = .04) and the infiltration of adjacent lung parenchyma (P = .01) are adverse prognostic factors.

Related: Ewing's Sarcoma


Bien E, Krawczyk M, Izycka-Swieszewska E, et al.
Deregulated systemic IL-10/IL-12 balance in advanced and poor prognosis paediatric soft tissue sarcomas.
Biomarkers. 2013; 18(3):204-15 [PubMed] Related Publications
CONTEXT: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear.
OBJECTIVE: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS).
MATERIALS AND METHODS: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls.
RESULTS: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis.
CONCLUSION: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS.

Related: IL10


Kreahling JM, Foroutan P, Reed D, et al.
Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas.
PLoS One. 2013; 8(3):e57523 [PubMed] Article available free on PMC after 20/08/2014 Related Publications
Sarcomas are rare and heterogeneous mesenchymal tumors affecting both pediatric and adult populations with more than 70 recognized histologies. Doxorubicin and ifosfamide have been the main course of therapy for treatment of sarcomas; however, the response rate to these therapies is about 10-20% in metastatic setting. Toxicity with the drug combination is high, response rates remain low, and improvement in overall survival, especially in the metastatic disease, remains negligible and new agents are needed. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by MK1775 has been reported to enhance the cytotoxic effect of DNA damaging agents in different types of carcinomas. In this study we investigated the therapeutic efficacy of MK1775 in various sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo both alone and in combination with gemcitabine, which is frequently used in the treatment of sarcomas. Our data demonstrate that MK1775 treatment as a single agent at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. Additionally, MK1775 significantly enhances the cytotoxic effect of gemcitabine in sarcoma cells lines with different p53 mutational status. In patient-derived bone and soft tissue sarcoma samples we showed that MK1775 alone and in combination with gemcitabine causes significant apoptotic cell death. Magnetic resonance imaging (MRI) and histopathologic studies showed that MK1775 induces significant cell death and terminal differentiation in a patient-derived xenograft mouse model of osteosarcoma in vivo. Our results together with the high safety profile of MK1775 strongly suggest that this drug can be used as a potential therapeutic agent in the treatment of both adult as well as pediatric sarcoma patients.

Related: Osteosarcoma Gemcitabine


Yi X, Long X, Xiao D, et al.
Rhabdomyosarcoma in adrenal region of a child with hypertension and fever: a case report and literature review.
J Pediatr Surg. 2013; 48(3):e5-8 [PubMed] Related Publications
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children but rarely involves the adrenal. We describe a case of alveolar rhabdomyosarcoma (ARMS) of the right adrenal in a 5-year-old boy with a characteristic history of hypertension and recurrent fever. On surveillance imaging, a right adrenal mass was incidentally detected, and a right adrenalectomy was subsequently performed. After the surgery, the fever disappeared simultaneously, and the blood pressure gradually returned to normal level. This is the first reported case in children.

Related: Rhabdomyosarcoma


Cassinelli G, Lanzi C, Tortoreto M, et al.
Antitumor efficacy of the heparanase inhibitor SST0001 alone and in combination with antiangiogenic agents in the treatment of human pediatric sarcoma models.
Biochem Pharmacol. 2013; 85(10):1424-32 [PubMed] Related Publications
The activity of heparanase is responsible for heparan sulfate cleavage, thus resulting in the release of heparan sulfate-bound growth factors. Since heparanase activity is upregulated in several tumor types and is implicated in the malignant behavior, the enzyme is regarded as a promising target for antitumor therapy. Based on previous evidence that the heparanase inhibitor SST0001, a non-anticoagulant N-acetylated glycol split heparin, is effective against an Ewing's sarcoma model, the present study was performed to extend the preclinical evaluation of SST0001 to a panel of pediatric sarcoma models, representative of various tumor histotypes (soft tissue and bone sarcomas) and to further elucidate its mode of action. SST0001 treatment downregulated several angiogenic factors in the conditioned media of sarcoma cells, inhibited the pro-invasive effect of heparin-binding factors (VEGF, bFGF, HGF, PDGF), and abrogated PDGF receptor tyrosine phosphorylation. Subcutaneous administration of SST0001 was very effective, resulting in a significant growth inhibition (range, 64-95%) of all tested tumor xenografts. The efficacy of SST0001 was enhanced in combination with antiangiogenic agents (bevacizumab, sunitinib) as documented by the high rate of complete response. The synergistic effect of SST0001 in combination with antiangiogenic agents is consistent with the heparanase mode of action and with the relevant role of heparin-binding proangiogenic/growth factors in the malignant behavior of sarcoma cells.

Related: Angiogenesis Inhibitors Bone Cancers Angiogenesis and Cancer Osteosarcoma Rhabdomyosarcoma Sunitinib (Sutent) Bevacizumab (Avastin)


Mosquera JM, Sboner A, Zhang L, et al.
Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma.
Genes Chromosomes Cancer. 2013; 52(6):538-50 [PubMed] Article available free on PMC after 01/06/2014 Related Publications
Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so-called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF-NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7-month-old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT-PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3-month-old and a 4-week-old child. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2-rearranged spindle cell RMS occurring in young childhood and the so-called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2).

Related: Chromosome 8 FISH Rhabdomyosarcoma


Thornton KA, Chen AR, Trucco MM, et al.
A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma.
Int J Cancer. 2013; 133(4):997-1005 [PubMed] Article available free on PMC after 15/08/2014 Related Publications
There are few effective therapies for high-risk sarcomas. Initial chemosensitivity is often followed by relapse. In vitro, mammalian target of rapamycin (mTOR) inhibition potentiates the efficacy of chemotherapy on resistant sarcoma cells. Although sarcoma trials using mTOR inhibitors have been disappointing, these drugs were used as maintenance. We conducted a Phase I/II clinical trial to test the ability of temsirolimus to potentiate the cytotoxic effect of liposomal doxorubicin and present here the dose-finding portion of this study. Adult and pediatric patients with recurrent or refractory sarcomas were treated with increasing doses of liposomal doxorubicin and temsirolimus using a continual reassessment method for escalation, targeting a dose-limiting toxicity rate of 20%. Blood samples were drawn before and after the first dose of temsirolimus in Cycles 1 and 2 for pharmacokinetic analysis. The maximally tolerated dose combination was liposomal doxorubicin 30 mg/m(2) monthly with temsirolimus 20 mg/m(2) weekly. Hematologic toxicity was common but manageable. Dose-limiting toxicities were primarily renal. Concurrent administration of liposomal doxorubicin resulted in increased exposure to sirolimus, the active metabolite of temsirolimus. Thus, the combination of liposomal doxorubicin and temsirolimus is safe for heavily pretreated sarcoma patients. Co-administration with liposomal doxorubicin did not alter temsirolimus pharmacokinetics, but increased exposure to its active metabolite.

Related: Bone Cancers Doxorubicin Temsirolimus (Torisel)


Franco A, Henderson PR, McDonough CH
Unusual Concentration of Tc-99m methylendiphosphonate in Rhabdomyosarcoma.
J Radiol Case Rep. 2012; 6(9):29-34 [PubMed] Article available free on PMC after 15/08/2014 Related Publications
Extraosseous accumulation of bone-seeking agents is rare, but has been previously reported in pediatric sarcomas and neuroblastomas. We present an unusual case of a 5-month-old male with an abdominal mass observed clinically by his parents and referring pediatrician. Contrast abdominal computerized tomography confirmed the presence of a large pelvic mass that was diagnosed pathologically as embryonal rhabdomyosarcoma. A bone scintigraphy that was performed for staging of the disease revealed accumulation of the radiopharmaceutical in the tumor. There was no evidence for skeletal metastatic disease. This case further demonstrates the nonspecificity of soft-tissue tumor uptake on bone scintigraphy.


Chen J, Chang J, Lew P, et al.
Nuclear scintigraphy findings for Askin tumor with In111-pentetreotide, Tc99m-MIBI and F18-FDG.
J Radiol Case Rep. 2012; 6(10):32-9 [PubMed] Article available free on PMC after 15/08/2014 Related Publications
Askin tumor is a rare disease which had previously been reported as being thallium-201 and gallium-67 avid. Varying data regarding 18F- fluorodeoxyglucose metabolism has been described with Ewing family of soft tissue tumors. In this case, we present a patient found to have an Askin tumor of the left chest wall which demonstrated indium-111 pentetreotide and technetium-99m MIBI avidity. The lesion did not show 18F- fluorodeoxyglucose hypermetabolism in this case despite the aggressiveness of the tumor. The patient was treated with surgical excision of the tumor and chemotherapy. Subsequently, contrast enhanced CT, indium-111 pentetreotide and technetium 99m-MIBI showed that the lesion had regressed. These findings suggest that Askin tumor can demonstrate Indium-111 pentetreotide and technetium 99m-MIBI uptake and need not be hypermetabolic on 18F-fluorodeoxyglucose exam.

Related: Bone Cancers Ewing's Sarcoma


Kuru TH, Roethke MC, Nyarangi-Dix J, et al.
Pediatric case report on magnetic resonance imaging/transrectal ultrasound-fusion biopsy of rhabdomyosarcoma of the bladder/prostate: a new tool to reduce therapy-associated morbidity?
Urology. 2013; 81(2):417-20 [PubMed] Related Publications
Rhabdomyosarcomas are the most common soft tissue sarcomas in children. Here we present management of an 18-month-old boy with metastatic rhabdomyosarcoma of the bladder/prostate. After radiochemotherapy, high-spatial-resolution 3-Tesla multiparametric magnetic resonance imaging (MRI) showed regressive systemic disease but a residual mass at the right seminal vesicle. For histologic re-evaluation, 3-dimensional-controlled stereotactic MRI/transrectal ultrasound (TRUS)-fusion biopsy specimens were taken. Because histologic analysis showed nonvital tissue, a decision could be made against adjuvant radical cystoprostatectomy. Advanced 3-Tesla imaging and MRI/TRUS-fusion biopsies in children are feasible and represent an effective tool to examine suspicious pelvic lesions. Depending on histology, this can lead to a significant reduction of therapy-associated morbidity.

Related: Prostate Cancer Bladder Cancer Bladder Cancer - Molecular Biology


Kim HY, Cho YH, Byun SY, Park KH
A case of congenital infantile fibrosarcoma of sigmoid colon manifesting as pneumoperitoneum in a newborn.
J Korean Med Sci. 2013; 28(1):160-3 [PubMed] Article available free on PMC after 15/08/2014 Related Publications
Congenital infantile fibrosarcoma (CIF) is a rare soft-tissue tumor in the pediatric age group and seldom involves the gastrointestinal tract. A 2-day-old boy was transferred to our hospital with a pneumpoperitoneum. After emergency operation, we could find a solid mass wrapping around a sigmoid colon and performed a segmental resection of sigmoid colon including a mass. Histopathologic examination showed an infantile fibrosarcoma origining from the muscular layer of colon. The baby was discharged on the 17th hospital day and followed for 1 yr without recurrence.


Crozier E, Rihani J, Koral K, et al.
Embryonal rhabdomyosarcoma of the auricle in a child.
Pediatr Int. 2012; 54(6):945-7 [PubMed] Related Publications
We describe the diagnosis and management of a child with embryonal rhabdomyosarcoma of the auricle and emphasize both clinical and radiological findings of this rare condition. A nine-year-old boy presented for evaluation of a slowly enlarging left auricle mass. The mass was nodular, violaceous, semi-translucent, and hyperpigmented with an overlying pseudo-vesicular plaque. The mass appeared to involve the left cavum concha, root of the helix, superior aspect of the external auditory canal, the tragus and extend to a deep preauricular component. MR imaging documented a lobulated soft tissue mass surrounding the external auditory canal with superficial involvement of the pinna. Incisional biopsy of the mass suggested embryonal rhabdomyosarcoma. The tumor was completely removed by total auriculectomy and lateral temporal bone resection. The final diagnosis was embryonal rhabdomyosarcoma. Although rare, otolaryngologists, pediatricians, and radiologists need to consider rhabdomyosarcoma in the differential diagnosis of auricle mass in children.


Morris P, Dickman PS, Seidel MJ
Ewing's sarcoma/primitive neuroectodermal tumor of the proximal humeral epiphysis.
Orthopedics. 2013; 36(1):e113-6 [PubMed] Related Publications
Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of bone is a rare childhood tumor most commonly located in the metadiaphysis. In skeletally immature patients, lesions of the epiphysis are rarely malignant, with the most common diagnosis being chondroblastoma. This article presents a case of ES/PNET of the proximal humeral epiphysis in a 12-year-old boy. To the authors' knowledge, this is the first reported case of epiphyseal ES/PNET confirmed with molecular testing. Radiographs of the patient's painful shoulder showed a well-defined lytic lesion within the humeral epiphysis. Magnetic resonance imaging suggested a chondroid tumor with surrounding edema. Based on the imaging characteristics, the patient's age, and the lesion's location, a preliminary diagnosis of chondroblastoma was made. A trochar biopsy of the lesion demonstrated a small, round, blue cell tumor on frozen section. Subsequently, immunohistochemical staining was uniformly positive in a membrane pattern for CD99, and molecular diagnostic testing demonstrated a EWSR1/FLI1 fusion transcript, confirming the pathologic diagnosis of ES/PNET. Although metadiaphyseal locations for ES/PNET are most common, this case adds to previously reported cases of epiphyseal ES/PNET, suggesting that the diagnosis be considered for pediatric epiphyseal tumors. This case also demonstrates why following rigorous oncologic treatment algorithms by obtaining a limited trochar biopsy, even in the case of a confident radiographic diagnosis, is critically important; the biopsy results can lead to a major change in treatment and avoid contamination of a larger area of soft tissue and bone.

Related: Bone Cancers Ewing's Sarcoma


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