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18-12-2024 | Rhabdomyosarcoma | REVIEW

Rhabdomyosarcoma in children and young adults

Authors: Sonja Chen, Anna M. Kelsey, Erin R. Rudzinski

Published in: Virchows Archiv | Issue 1/2025

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood, accounting for 3% of all pediatric malignancies and 50% of all pediatric soft tissue sarcomas. In adolescents and young adults (AYA) however, RMS comprises only 6.5% of all soft tissue sarcomas. Historically, diagnosis and treatment of RMS was based on histologic recognition of the alveolar subtype, which was associated with a worse prognosis. Within the past 20 years, the biologic characteristics of RMS have become clearer, with canonical fusion drivers, PAX3/7::FOXO1, characterizing the alveolar subtype (ARMS) and in turn associated with poor outcome, while chromosomal gains/losses in addition to RAS pathway alterations characterize the embryonal subtype (ERMS). Accordingly, detection of a FOXO1 gene fusion has become a commonplace diagnostic and prognostic tool allowing tumors to be treated based on presence or absence of a FOXO1 gene fusion. However, these cytogenetic and molecular alterations represent only a portion of the molecular landscape found in RMS, and other alterations are found with increasing frequency in various subsets of RMS. Clinical trials basing risk stratification on the presence or absence of the canonical PAX3/7::FOXO1 fusions have had success in identifying the poor responders. Due to poor outcomes, the presence of MYOD1 and TP53 alterations which are common in spindle cell sclerosing RMS (SSRMS) and RMS with anaplasia have also been integrated into trial risk stratification. Therefore, complete histologic and immunophenotypic characterization remain important to better recognize and study these rare subsets of RMS. This article will discuss the challenges of RMS classification including how to combine morphologic, immunophenotypic and molecular data to arrive at an integrated diagnosis. The use of newer techniques such as liquid biopsy and methylation profiling, will also continue to shape the classification of RMS and may further refine risk stratification and prognosis.

Oberoi S, Crane JN, Haduong JH, Rudzinski ER, Wolden SL, Dasgupta R, Linardic CM, Weiss AR, Venkatramani R, the Children's Oncology Group Soft Tissue Sarcoma C (2023) Children's oncology group's 2023 blueprint for research: Soft tissue sarcomas. Pediatr Blood Cancer 70 Suppl 6:e30556. https://doi.org/10.1002/pbc.30556

Ferrari A, Miceli R, Rey A, Oberlin O, Orbach D, Brennan B, Mariani L, Carli M, Bisogno G, Cecchetto G, De Salvo GL, Casanova M, Vannoesel MM, Kelsey A, Stevens MC, Devidas M, Pappo AS, Spunt SL (2011) Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47:724–731. https://doi.org/10.1016/j.ejca.2010.11.013CrossRefPubMed

Bleyer A OLM, Barr R, Ries LAG (eds) (2006) Cancer epidemiology in older adolescents and young adults 15 to 29 years of age, including SEER incidence and survival: 1975-2000. . National Cancer Institute, NIH, Bethesda, MD, pp

Hibbitts E, Chi YY, Hawkins DS, Barr FG, Bradley JA, Dasgupta R, Meyer WH, Rodeberg DA, Rudzinski ER, Spunt SL, Skapek SX, Wolden SL, Arndt CAS (2019) Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: a report from the Children’s Oncology Group. Cancer Med 8:6437–6448. https://doi.org/10.1002/cam4.2504CrossRefPubMedPubMedCentral

Shern JF, Selfe J, Izquierdo E, Patidar R, Chou HC, Song YK, Yohe ME, Sindiri S, Wei J, Wen X, Rudzinski ER, Barkauskas DA, Lo T, Hall D, Linardic CM, Hughes D, Jamal S, Jenney M, Chisholm J, Brown R, Jones K, Hicks B, Angelini P, George S, Chesler L, Hubank M, Kelsey A, Gatz SA, Skapek SX, Hawkins DS, Shipley JM, Khan J (2021) Genomic classification and clinical outcome in rhabdomyosarcoma: a report from an International Consortium. J Clin Oncol 39:2859–2871. https://doi.org/10.1200/JCO.20.03060CrossRefPubMedPubMedCentral

Guersant M (1854) Polypes du vagin chez une petite fille de treize mois Monit Hopit 2:187

Rudzinski ER, Kelsey A, Vokuhl C, Linardic CM, Shipley J, Hettmer S, Koscielniak E, Hawkins DS, Bisogno G (2021) Pathology of childhood rhabdomyosarcoma: a consensus opinion document from the Children’s Oncology Group, European Paediatric Soft Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. Pediatr Blood Cancer 68:e28798. https://doi.org/10.1002/pbc.28798CrossRefPubMed

Giannikopoulos P, Parham DM (2021) Rhabdomyosarcoma: how advanced molecular methods are shaping the diagnostic and therapeutic paradigm. Pediatr Dev Pathol 24:395–404. https://doi.org/10.1177/10935266211013621CrossRefPubMed

Agaram NP (2022) Evolving classification of rhabdomyosarcoma. Histopathology 80:98–108. https://doi.org/10.1111/his.14449CrossRefPubMedPubMedCentral

10.

Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS (2001) Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 19:3091–3102. https://doi.org/10.1200/JCO.2001.19.12.3091CrossRefPubMed

11.

Little DJ, Ballo MT, Zagars GK, Pisters PW, Patel SR, El-Naggar AK, Garden AS, Benjamin RS (2002) Adult rhabdomyosarcoma: outcome following multimodality treatment. Cancer 95:377–388. https://doi.org/10.1002/cncr.10669CrossRefPubMed

12.

Shern JF, Chen L, Chmielecki J, Wei JS, Patidar R, Rosenberg M, Ambrogio L, Auclair D, Wang J, Song YK, Tolman C, Hurd L, Liao H, Zhang S, Bogen D, Brohl AS, Sindiri S, Catchpoole D, Badgett T, Getz G, Mora J, Anderson JR, Skapek SX, Barr FG, Meyerson M, Hawkins DS, Khan J (2014) Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors. Cancer Discov 4:216–231. https://doi.org/10.1158/2159-8290.CD-13-0639CrossRefPubMedPubMedCentral

13.

Rudzinski ER, Teot LA, Anderson JR, Moore J, Bridge JA, Barr FG, Gastier-Foster JM, Skapek SX, Hawkins DS, Parham DM (2013) Dense pattern of embryonal rhabdomyosarcoma, a lesion easily confused with alveolar rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Am J Clin Pathol 140:82–90. https://doi.org/10.1309/AJCPA1WN7ARPCMKQCrossRefPubMed

14.

Wachtel M, Runge T, Leuschner I, Stegmaier S, Koscielniak E, Treuner J, Odermatt B, Behnke S, Niggli FK, Schafer BW (2006) Subtype and prognostic classification of rhabdomyosarcoma by immunohistochemistry. J Clin Oncol 24:816–822. https://doi.org/10.1200/JCO.2005.03.4934CrossRefPubMed

15.

Rudzinski ER, Anderson JR, Lyden ER, Bridge JA, Barr FG, Gastier-Foster JM, Bachmeyer K, Skapek SX, Hawkins DS, Teot LA, Parham DM (2014) Myogenin, AP2beta, NOS-1, and HMGA2 are surrogate markers of fusion status in rhabdomyosarcoma: a report from the soft tissue sarcoma committee of the children’s oncology group. Am J Surg Pathol 38:654–659. https://doi.org/10.1097/PAS.0000000000000195CrossRefPubMedPubMedCentral

16.

Apellaniz-Ruiz M, McCluggage WG, Foulkes WD (2021) DICER1-associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: pathology, molecular genetics, and indications for molecular testing. Genes Chromosomes Cancer 60:217–233. https://doi.org/10.1002/gcc.22913CrossRefPubMed

17.

Schultz KAP, Williams GM, Kamihara J, Stewart DR, Harris AK, Bauer AJ, Turner J, Shah R, Schneider K, Schneider KW, Carr AG, Harney LA, Baldinger S, Frazier AL, Orbach D, Schneider DT, Malkin D, Dehner LP, Messinger YH, Hill DA (2018) DICER1 and associated conditions: identification of at-risk individuals and recommended surveillance strategies. Clin Cancer Res 24:2251–2261. https://doi.org/10.1158/1078-0432.CCR-17-3089CrossRefPubMedPubMedCentral

18.

Gonzalez IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP (2022) DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol 35:4–22. https://doi.org/10.1038/s41379-021-00905-8CrossRefPubMed

19.

Dehner LP, Jarzembowski JA, Hill DA (2012) Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations. Mod Pathol 25:602–614. https://doi.org/10.1038/modpathol.2011.185CrossRefPubMed

20.

Devins KM, Young RH, Ghioni M, Burandt E, Bennett JA, Oliva E (2022) Embryonal rhabdomyosarcoma of the uterine cervix: a clinicopathologic study of 94 cases emphasizing issues in differential diagnosis staging, and prognostic factors. Am J Surg Pathol 46:1477–1489. https://doi.org/10.1097/PAS.0000000000001933CrossRefPubMed

21.

Bennett JA, Ordulu Z, Young RH, Pinto A, Van de Vijver K, Burandt E, Wanjari P, Shah R, de Kock L, Foulkes WD, McCluggage WG, Ritterhouse LL, Oliva E (2021) Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations. Mod Pathol 34:1750–1762. https://doi.org/10.1038/s41379-021-00821-xCrossRefPubMed

22.

Kommoss FKF, Stichel D, Mora J, Esteller M, Jones DTW, Pfister SM, Brack E, Wachtel M, Bode PK, Sinn HP, Schmidt D, Mentzel T, Kommoss F, Sahm F, von Deimling A, Koelsche C (2021) Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup. Mod Pathol 34:1558–1569. https://doi.org/10.1038/s41379-021-00804-yCrossRefPubMedPubMedCentral

23.

Koelsche C, Mynarek M, Schrimpf D, Bertero L, Serrano J, Sahm F, Reuss DE, Hou Y, Baumhoer D, Vokuhl C, Flucke U, Petersen I, Bruck W, Rutkowski S, Zambrano SC, Garcia Leon JL, Diaz Coronado RY, Gessler M, Tirado OM, Mora J, Alonso J, Garcia Del Muro X, Esteller M, Sturm D, Ecker J, Milde T, Pfister SM, Korshunov A, Snuderl M, Mechtersheimer G, Schuller U, Jones DTW, von Deimling A (2018) Primary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations. Acta Neuropathol 136:327–337. https://doi.org/10.1007/s00401-018-1871-6CrossRefPubMed

24.

Das A, Roy P, Modi SK, Achari RB, Sen S, Singh A, Sukumaran R, Bhattacharyya A (2019) Germline DICER1-mutant intracranial sarcoma with dual chondroid and spindle cell morphology and pulmonary metastases treated with multimodal therapy. Pediatr Blood Cancer 66:e27744. https://doi.org/10.1002/pbc.27744CrossRefPubMed

25.

Mitchell SG, Schultz KAP, Rytting H, Kostelecky N, Hill DA, Dehner LP (2022) DICER1-associated hepatic cystic neoplasm with pleuropulmonary blastoma-like features: a novel clinicopathologic diagnosis. Mod Pathol 35:676–679. https://doi.org/10.1038/s41379-021-00947-yCrossRefPubMed

26.

Schultz KAP, Nelson A, Harris AK, Finch M, Field A, Jarzembowski JA, Wilhelm M, Mize W, Kreiger P, Conard K, Walter A, Olson T, Mitchell S, Runco DV, Bechtel A, Klawinski D, Bradfield S, Gettinger K, Stewart DR, Messinger Y, Dehner LP, Ashley Hill D (2020) Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation. Mod Pathol 33:1922–1929. https://doi.org/10.1038/s41379-020-0558-4CrossRefPubMedPubMedCentral

27.

Shenoy A, Alvarez E, Chi YY, Li M, Shern JF, Khan J, Hiniker SM, Granberg CF, Hawkins DS, Parham DM, Teot LA, Rudzinski ER (2021) The prognostic significance of anaplasia in childhood rhabdomyosarcoma: a report from the Children’s Oncology Group. Eur J Cancer 143:127–133. https://doi.org/10.1016/j.ejca.2020.10.018CrossRefPubMed

28.

Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L, Rodriguez-Galindo C, Teot LA, Malkin D (2014) Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers. Cancer 120:1068–1075. https://doi.org/10.1002/cncr.28507CrossRefPubMed

29.

Fair D, Maese L, Chi YY, Li M, Hawkins DS, Venkatramani R, Rudzinski E, Parham D, Teot L, Malkin D, Plon SE, Li H, Sabo A, Lupo PJ, Schiffman JD (2023) TP53 germline pathogenic variant frequency in anaplastic rhabdomyosarcoma: a Children's Oncology Group report. Pediatr Blood Cancer:e30413. https://doi.org/10.1002/pbc.30413

30.

Ayan I, Dogan O, Kebudi R, Bavbek B, Alatli C, Dervisoglu S, Disci R, Demiryont M (1997) Immunohistochemical detection of p53 protein in rhabdomyosarcoma: association with clinicopathological features and outcome. J Pediatr Hematol Oncol 19:48–53. https://doi.org/10.1097/00043426-199701000-00007CrossRefPubMed

31.

Leuschner I, Langhans I, Schmitz R, Harms D, Mattke A, Treuner J, Kiel Pediatric Tumor R, the German Cooperative Soft Tissue Sarcoma S (2003) p53 and mdm-2 expression in Rhabdomyosarcoma of childhood and adolescence: clinicopathologic study by the Kiel Pediatric Tumor Registry and the German Cooperative Soft Tissue Sarcoma Study Pediatr Dev Pathol 6:128-136. https://doi.org/10.1007/s10024-001-0097-z

32.

Tomassen T, Kester LA, Tops BB, Driehuis E, van Noesel MM, van Ewijk R, van Gorp JM, Hulsker CC, Terwisscha-van Scheltinga SEJ, Merks HHM, Flucke U, Hiemcke-Jiwa LS (2021) Loss of H3K27me3 occurs in a large subset of embryonal rhabdomyosarcomas: immunohistochemical and molecular analysis of 25 cases. Ann Diagn Pathol 52:151735. https://doi.org/10.1016/j.anndiagpath.2021.151735CrossRefPubMed

33.

Bridge JA, Liu J, Weibolt V, Baker KS, Perry D, Kruger R, Qualman S, Barr F, Sorensen P, Triche T, Suijkerbuijk R (2000) Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study. Genes Chromosomes Cancer 27:337–344. https://doi.org/10.1002/(sici)1098-2264(200004)27:4%3c337::aid-gcc1%3e3.0.co;2-1CrossRefPubMed

34.

Bridge JA, Liu J, Qualman SJ, Suijkerbuijk R, Wenger G, Zhang J, Wan X, Baker KS, Sorensen P, Barr FG (2002) Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes. Genes Chromosomes Cancer 33:310–321. https://doi.org/10.1002/gcc.10026CrossRefPubMed

35.

Skapek SX, Ferrari A, Gupta AA, Lupo PJ, Butler E, Shipley J, Barr FG, Hawkins DS (2019) Rhabdomyosarcoma. Nat Rev Dis Primers 5:1. https://doi.org/10.1038/s41572-018-0051-2CrossRefPubMedPubMedCentral

36.

Agaram NP, Huang SC, Tap WD, Wexler LH, Antonescu CR (2022) Clinicopathologic and survival correlates of embryonal rhabdomyosarcoma driven by RAS/RAF mutations. Genes Chromosomes Cancer 61:131–137. https://doi.org/10.1002/gcc.23010CrossRefPubMed

37.

Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O (2010) Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 28:2151–2158. https://doi.org/10.1200/JCO.2009.26.3814CrossRefPubMed

38.

de Traux De Wardin H, Cyrta J, Dermawan JK, Guillemot D, Orbach D, Aerts I, Pierron G, Antonescu CR (2024) FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma. Genes Chromosomes Cancer 63:e23232.https://doi.org/10.1002/gcc.23232

39.

Weiss AR, Harrison DJ (2024) Soft tissue sarcomas in adolescents and young adults. J Clin Oncol 42:675–685. https://doi.org/10.1200/JCO.23.01275CrossRefPubMed

40.

Tsokos M, Webber BL, Parham DM, Wesley RA, Miser A, Miser JS, Etcubanas E, Kinsella T, Grayson J, Glatstein E et al (1992) Rhabdomyosarcoma A new classification scheme related to prognosis. Arch Pathol Lab Med 116:847–855PubMed

41.

Kohashi K, Bode-Lesniewska, Beata (2020) Alveolar rhabdomyosarcoma. In: Cunha IW (ed) WHO classification of tumours editorial board. Soft tissue and bone tumours [Internet]. International Agency for Research on Cancer, Lyon (France), pp

42.

Rutland CD, Gedallovich J, Wang A, Zdravkovic S, Varma S, Hornick JL, Charville GW (2023) Diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification. Histopathology 83:49–56. https://doi.org/10.1111/his.14898CrossRefPubMed

43.

Haduong JH, Heske CM, Allen-Rhoades W, Xue W, Teot LA, Rodeberg DA, Donaldson SS, Weiss A, Hawkins DS, Venkatramani R (2022) An update on rhabdomyosarcoma risk stratification and the rationale for current and future Children’s Oncology Group clinical trials. Pediatr Blood Cancer 69:e29511. https://doi.org/10.1002/pbc.29511CrossRefPubMedPubMedCentral

44.

Raze T, Lapouble E, Lacour B, Guissou S, Defachelles AS, Gaspar N, Delattre O, Pierron G, Desandes E (2023) PAX-FOXO1 fusion status in children and adolescents with alveolar rhabdomyosarcoma: impact on clinical, pathological, and survival features. Pediatr Blood Cancer 70:e30228. https://doi.org/10.1002/pbc.30228CrossRefPubMed

45.

Stegmaier S, Poremba C, Schaefer KL, Leuschner I, Kazanowska B, Bekassy AN, Bielack SS, Klingebiel T, Koscielniak E (2011) Prognostic value of PAX-FKHR fusion status in alveolar rhabdomyosarcoma: a report from the cooperative soft tissue sarcoma study group (CWS). Pediatr Blood Cancer 57:406–414. https://doi.org/10.1002/pbc.22958CrossRefPubMed

46.

Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A, Meloni-Ehrig A, Bridge JA (2010) Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family. Genes Chromosomes Cancer 49:224–236. https://doi.org/10.1002/gcc.20731CrossRefPubMedPubMedCentral

47.

Di Carlo D, Chargari C, Scoazec JY, Cotteret S, Felix A, Moalla S, Temam S, Minard-Colin V (2021) PAX3-NCOA1 alveolar rhabdomyosarcoma of the tongue: a rare entity with challenging diagnosis and management. Pediatr Blood Cancer 68:e29288. https://doi.org/10.1002/pbc.29288CrossRefPubMed

48.

Liu J, Guzman MA, Pezanowski D, Patel D, Hauptman J, Keisling M, Hou SJ, Papenhausen PR, Pascasio JM, Punnett HH, Halligan GE, de Chadarevian JP (2011) FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma. Mod Pathol 24:1327–1335. https://doi.org/10.1038/modpathol.2011.98CrossRefPubMed

49.

Barr FG, Qualman SJ, Macris MH, Melnyk N, Lawlor ER, Strzelecki DM, Triche TJ, Bridge JA, Sorensen PH (2002) Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Res 62:4704–4710PubMed

50.

Lewis JT, Oliveira AM, Nascimento AG, Schembri-Wismayer D, Moore EA, Olsen KD, Garcia JG, Lonzo ML, Lewis JE (2012) Low-grade sinonasal sarcoma with neural and myogenic features: a clinicopathologic analysis of 28 cases. Am J Surg Pathol 36:517–525. https://doi.org/10.1097/PAS.0b013e3182426886CrossRefPubMed

51.

Wang X, Bledsoe KL, Graham RP, Asmann YW, Viswanatha DS, Lewis JE, Lewis JT, Chou MM, Yaszemski MJ, Jen J, Westendorf JJ, Oliveira AM (2014) Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma. Nat Genet 46:666–668. https://doi.org/10.1038/ng.2989CrossRefPubMedPubMedCentral

52.

Huang SC, Ghossein RA, Bishop JA, Zhang L, Chen TC, Huang HY, Antonescu CR (2016) Novel PAX3-NCOA1 fusions in biphenotypic sinonasal sarcoma with focal rhabdomyoblastic differentiation. Am J Surg Pathol 40:51–59. https://doi.org/10.1097/PAS.0000000000000492CrossRefPubMedPubMedCentral

53.

Bhele S, Chrisinger JSA, Farrell NF, Van Tine BA, Raptis CA, Chernock RD (2023) Biphenotypic sinonasal sarcoma with a novel PAX7::PPARGC1 fusion: expanding the spectrum of gene fusions beyond the PAX3 gene. Head Neck Pathol 17:826–831. https://doi.org/10.1007/s12105-023-01566-6CrossRefPubMedPubMedCentral

54.

Rooper LM, Huang SC, Antonescu CR, Westra WH, Bishop JA (2016) Biphenotypic sinonasal sarcoma: an expanded immunoprofile including consistent nuclear beta-catenin positivity and absence of SOX10 expression. Hum Pathol 55:44–50. https://doi.org/10.1016/j.humpath.2016.04.009CrossRefPubMedPubMedCentral

55.

Andreasen S, Bishop JA, Hellquist H, Hunt J, Kiss K, Rinaldo A, Skalova A, Willems SM, Williams M, Ferlito A (2018) Biphenotypic sinonasal sarcoma: demographics, clinicopathological characteristics, molecular features, and prognosis of a recently described entity. Virchows Arch 473:615–626. https://doi.org/10.1007/s00428-018-2426-xCrossRefPubMed

56.

Wong WJ, Lauria A, Hornick JL, Xiao S, Fletcher JA, Marino-Enriquez A (2016) Alternate PAX3-FOXO1 oncogenic fusion in biphenotypic sinonasal sarcoma. Genes Chromosomes Cancer 55:25–29. https://doi.org/10.1002/gcc.22295CrossRefPubMed

57.

Shenoy A XW, Qumseya A, Gupta A, Lautz T, Wolden S, Metts J, Reshmi S, Wagner E, Venkatramani R, Chen S, Arnold M, Rudzinski E, Teot L (2023) Characterization of rhabdomyosarcoma with PAX7::FOXO1 fusions: a report from the Soft Tissue Committee of the Children's Oncology Group. Connective Tissue Oncology Society Annual Meeting, Dublin, Ireland, pp

58.

Agaram NP, Chen CL, Zhang L, LaQuaglia MP, Wexler L, Antonescu CR (2014) Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosomes Cancer 53:779–787. https://doi.org/10.1002/gcc.22187CrossRefPubMedPubMedCentral

59.

Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, Zin A, Agaram NP, LaQuaglia MP, Wexler LH, Antonescu CR (2016) A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases. Am J Surg Pathol 40:224–235. https://doi.org/10.1097/PAS.0000000000000538CrossRefPubMedPubMedCentral

60.

Van Antwerp ME, Chen DG, Chang C, Prochownik EV (1992) A point mutation in the MyoD basic domain imparts c-Myc-like properties. Proc Natl Acad Sci U S A 89:9010–9014. https://doi.org/10.1073/pnas.89.19.9010CrossRefPubMedPubMedCentral

61.

Tsai JW, ChangChien YC, Lee JC, Kao YC, Li WS, Liang CW, Liao IC, Chang YM, Wang JC, Tsao CF, Yu SC, Huang HY (2019) The expanding morphological and genetic spectrum of MYOD1 -mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases. Histopathology 74:933–943. https://doi.org/10.1111/his.13819CrossRefPubMed

62.

Kohsaka S, Shukla N, Ameur N, Ito T, Ng CK, Wang L, Lim D, Marchetti A, Viale A, Pirun M, Socci ND, Qin LX, Sciot R, Bridge J, Singer S, Meyers P, Wexler LH, Barr FG, Dogan S, Fletcher JA, Reis-Filho JS, Ladanyi M (2014) A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations. Nat Genet 46:595–600. https://doi.org/10.1038/ng.2969CrossRefPubMedPubMedCentral

63.

Shukla N, Ameur N, Yilmaz I, Nafa K, Lau CY, Marchetti A, Borsu L, Barr FG, Ladanyi M (2012) Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res 18:748–757. https://doi.org/10.1158/1078-0432.CCR-11-2056CrossRefPubMed

64.

Mosquera JM, Sboner A, Zhang L, Kitabayashi N, Chen CL, Sung YS, Wexler LH, LaQuaglia MP, Edelman M, Sreekantaiah C, Rubin MA, Antonescu CR (2013) Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma. Genes Chromosomes Cancer 52:538–550. https://doi.org/10.1002/gcc.22050CrossRefPubMed

65.

Whittle S, Venkatramani R, Schonstein A, Pack SD, Alaggio R, Vokuhl C, Rudzinski ER, Wulf AL, Zin A, Gruver JR, Arnold MA, Merks JHM, Hettmer S, Koscielniak E, Barr FG, Hawkins DS, Bisogno G, Sparber-Sauer M (2022) Congenital spindle cell rhabdomyosarcoma: an international cooperative analysis. Eur J Cancer 168:56–64. https://doi.org/10.1016/j.ejca.2022.03.022CrossRefPubMedPubMedCentral

66.

Cyrta J, Gauthier A, Karanian M, Vieira AF, Cardoen L, Jehanno N, Bouvet M, Bouvier C, Komuta M, Le Loarer F, Orbach D, Rome A, Minard-Colin V, Brichard B, Pluchart C, Thebaud E, Renard M, Pannier S, Brisse H, Petit P, Benoist C, Schleiermacher G, Geoerger B, Vincent-Salomon A, Freneaux P, Pierron G (2021) Infantile rhabdomyosarcomas with VGLL2 rearrangement are not always an indolent disease: a study of 4 aggressive cases with clinical, pathologic, molecular, and radiologic findings. Am J Surg Pathol 45:854–867. https://doi.org/10.1097/PAS.0000000000001702CrossRefPubMed

67.

Xu B, Suurmeijer AJH, Agaram NP, Zhang L, Antonescu CR (2021) Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases. Histopathology 79:347–357. https://doi.org/10.1111/his.14323CrossRefPubMedPubMedCentral

68.

Dehner CA, Geiersbach K, Rowsey R, Murugan P, Broski SM, Meis JM, Rosenberg AE, Folpe AL (2023) Rhabdomyosarcoma arising in inflammatory rhabdomyoblastic tumor: a genetically distinctive subtype of rhabdomyosarcoma. Mod Pathol 36:100131. https://doi.org/10.1016/j.modpat.2023.100131CrossRefPubMed

69.

Le Loarer F, Cleven AHG, Bouvier C, Castex MP, Romagosa C, Moreau A, Salas S, Bonhomme B, Gomez-Brouchet A, Laurent C, Le Guellec S, Audard V, Giraud A, Ramos-Oliver I, Cleton-Jansen AM, Savci-Heijink DC, Kroon HM, Baud J, Pissaloux D, Pierron G, Sherwood A, Coindre JM, Bovee J, Larousserie F, Tirode F (2020) A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation. Mod Pathol 33:404–419. https://doi.org/10.1038/s41379-019-0323-8CrossRefPubMed

70.

Lewin J, Desai J, Smith K, Luen S, Wong D (2019) Lack of clinical activity with crizotinib in a patient with FUS rearranged rhabdomyosarcoma with ALK protein overexpression. Pathology 51:655–657. https://doi.org/10.1016/j.pathol.2019.07.004CrossRefPubMed

71.

Chen F, Wang J, Sun Y, Zhang J (2024) Mandibular rhabdomyosarcoma with TFCP2 rearrangement and osteogenic differentiation: a case misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma. Oral Surg Oral Med Oral Pathol Oral Radiol 137:e143–e149. https://doi.org/10.1016/j.oooo.2023.12.792CrossRefPubMed

72.

Plotzke JM, Rabah R, Robinson DR, Edmonds A, Bloom DA, Mody R, Heider A (2024) Primary intraosseous spindle cell rhabdomyosarcoma: a case report in an unusual location. Pediatr Dev Pathol:10935266241257547. https://doi.org/10.1177/10935266241257547

73.

Oudijk L, den Bakker MA, Hop WC, Cohen M, Charles AK, Alaggio R, Coffin CM, de Krijger RR (2012) Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases. Histopathology 60:E1-11. https://doi.org/10.1111/j.1365-2559.2012.04221.xCrossRefPubMed

74.

Antonescu CR, Sung YS, Zhang L, Agaram NP, Fletcher CD (2017) Recurrent SRF-RELA fusions define a novel subset of cellular myofibroma/myopericytoma: a potential diagnostic pitfall with sarcomas with myogenic differentiation. Am J Surg Pathol 41:677–684. https://doi.org/10.1097/PAS.0000000000000811CrossRefPubMedPubMedCentral

75.

Karanian M, Kelsey A, Paindavoine S, Duc A, Vanacker H, Hook L, Weinbreck N, Delfour C, Minard V, Baillard P, Blay JY, Pissaloux D, Tirode F (2020) SRF fusions other than with RELA expand the molecular definition of SRF-fused perivascular tumors. Am J Surg Pathol 44:1725–1735. https://doi.org/10.1097/PAS.0000000000001546CrossRefPubMed

76.

Arbajian E, Koster J, Vult von Steyern F, Mertens F (2018) Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature. Mod Pathol 31:93–100. https://doi.org/10.1038/modpathol.2017.113CrossRefPubMed

77.

Martinez AP, Fritchie KJ, Weiss SW, Agaimy A, Haller F, Huang HY, Lee S, Bahrami A, Folpe AL (2019) Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms. Mod Pathol 32:446–457. https://doi.org/10.1038/s41379-018-0145-0CrossRefPubMed

78.

Michal M, Rubin BP, Kazakov DV, Michalova K, Steiner P, Grossmann P, Hajkova V, Martinek P, Svajdler M, Agaimy A, Hadravsky L, Kalmykova AV, Konishi E, Heidenreich F, Michal M (2020) Inflammatory leiomyosarcoma shows frequent co-expression of smooth and skeletal muscle markers supporting a primitive myogenic phenotype: a report of 9 cases with a proposal for reclassification as low-grade inflammatory myogenic tumor. Virchows Arch 477:219–230. https://doi.org/10.1007/s00428-020-02774-zCrossRefPubMed

79.

Lee JC, Li WS, Kao YC, Chung YC, Huang HY (2021) Toward a unifying entity that encompasses most, but perhaps not all, inflammatory leiomyosarcomas and histiocyte-rich rhabdomyoblastic tumors. Mod Pathol 34:1434–1438. https://doi.org/10.1038/s41379-021-00797-8CrossRefPubMed

80.

Sukhanova M, Obeidin F, Streich L, Alexiev BA (2022) Inflammatory leiomyosarcoma/rhabdomyoblastic tumor: a report of two cases with novel genetic findings. Genes Chromosomes Cancer 61:653–661. https://doi.org/10.1002/gcc.23072CrossRefPubMedPubMedCentral

81.

Rekhi B, Bal M, Dharavath B, Dutt A, Pai P (2023) A rare case of a low-grade inflammatory leiomyosarcoma/histiocyte-rich rhabdomyoblastic tumor in the neck of an adolescent male. Turk Patoloji Derg 39:154–160. https://doi.org/10.5146/tjpath.2022.01577CrossRefPubMedPubMedCentral

82.

Odate T, Satomi K, Kubo T, Matsushita Y, Ueno T, Kurose A, Shomori K, Nakai T, Watanabe R, Segawa K, Ohshika S, Miyake N, Kudo S, Shimoi T, Kobayashi E, Komiyama M, Yoshimoto S, Nakatani F, Kawai A, Yatabe Y, Kohsaka S, Ichimura K, Ichikawa H, Yoshida A (2024) Inflammatory rhabdomyoblastic tumor: clinicopathologic and molecular analysis of 13 cases. Mod Pathol 37:100359. https://doi.org/10.1016/j.modpat.2023.100359CrossRefPubMed

83.

Cloutier JM, Charville GW, Mertens F, Sukov W, Fritchie K, Perry KD, Edgar M, Rowsey RA, Folpe AL (2021) Inflammatory Leiomyosarcoma" and “Histiocyte-rich Rhabdomyoblastic Tumor”: a clinicopathological, immunohistochemical and genetic study of 13 cases, with a proposal for reclassification as "inflammatory rhabdomyoblastic. Tumor Mod Pathol 34:758–769. https://doi.org/10.1038/s41379-020-00703-8CrossRefPubMed

84.

Baltres A, Salhi A, Houlier A, Pissaloux D, Tirode F, Haddad V, Karanian M, Ysmail-Dahlouk S, Boukendakdji F, Dahlouk D, Allaoua F, Metref M, Djeridane A, Fraitag S, de la Fouchardiere A (2019) Malignant melanoma with areas of rhabdomyosarcomatous differentiation arising in a giant congenital nevus with RAF1 gene fusion. Pigment Cell Melanoma Res 32:708–713. https://doi.org/10.1111/pcmr.12785CrossRefPubMed

85.

Reith JD, Donahue FI, Hornicek FJ (1999) Dedifferentiated parosteal osteosarcoma with rhabdomyosarcomatous differentiation. Skeletal Radiol 28:527–531. https://doi.org/10.1007/s002560050557CrossRefPubMed

86.

Gong LH, Su YB, Zhang W, Liu WF, Dong RF, Sun XQ, Zhang M, Ding Y (2021) Dedifferentiated central chondrosarcoma: a clinical, histopathological, and immunohistochemical analysis of 57 cases. Front Med (Lausanne) 8:746909. https://doi.org/10.3389/fmed.2021.746909CrossRefPubMed

87.

Alaggio R KA, Bailey KM, Bisogno G, Davis J, Dry SM, Konovalov D, Lazar A, O’Sullivan M, Rudzinski E, Venkatramani R, Vokuhl C, Zambrano E, Cohen M, Reyes-Múgica M (2023) Paediatric rhabdomyosarcoma histopathology reporting guide. International Collaboration on Cancer Reporting, Sydney, Australia, pp

88.

Hettmer S, Linardic CM, Kelsey A, Rudzinski ER, Vokuhl C, Selfe J, Ruhen O, Shern JF, Khan J, Kovach AR, Lupo PJ, Gatz SA, Schafer BW, Volchenboum S, Minard-Colin V, Koscielniak E, Hawkins DS, Bisogno G, Sparber-Sauer M, Venkatramani R, Merks JHM, Shipley J (2022) Molecular testing of rhabdomyosarcoma in clinical trials to improve risk stratification and outcome: a consensus view from European paediatric Soft tissue sarcoma Study Group, Children’s Oncology Group and Cooperative Weichteilsarkom-Studiengruppe. Eur J Cancer 172:367–386. https://doi.org/10.1016/j.ejca.2022.05.036CrossRefPubMed

89.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1CrossRefPubMed

90.

Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Holsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Bruck W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hanggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Muhleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Muller HL, Rutkowski S, von Hoff K, Fruhwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blumcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schuller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474. https://doi.org/10.1038/nature26000CrossRefPubMedPubMedCentral

91.

Mahoney SE, Yao Z, Keyes CC, Tapscott SJ, Diede SJ (2012) Genome-wide DNA methylation studies suggest distinct DNA methylation patterns in pediatric embryonal and alveolar rhabdomyosarcomas. Epigenetics 7:400–408. https://doi.org/10.4161/epi.19463CrossRefPubMedPubMedCentral

92.

Seki M, Nishimura R, Yoshida K, Shimamura T, Shiraishi Y, Sato Y, Kato M, Chiba K, Tanaka H, Hoshino N, Nagae G, Shiozawa Y, Okuno Y, Hosoi H, Tanaka Y, Okita H, Miyachi M, Souzaki R, Taguchi T, Koh K, Hanada R, Kato K, Nomura Y, Akiyama M, Oka A, Igarashi T, Miyano S, Aburatani H, Hayashi Y, Ogawa S, Takita J (2015) Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma. Nat Commun 6:7557. https://doi.org/10.1038/ncomms8557CrossRefPubMed

93.

Clay MR, Patel A, Tran Q, Hedges DJ, Chang TC, Stewart E, Charville G, Cline C, Dyer MA, Orr BA (2021) Methylation profiling reveals novel molecular classes of rhabdomyosarcoma. Sci Rep 11:22213. https://doi.org/10.1038/s41598-021-01649-wCrossRefPubMedPubMedCentral

94.

Saoud C, Dermawan JK, Sharma AE, Tap W, Wexler LH, Antonescu CR (2024) Genomic profiling of pleomorphic rhabdomyosarcoma reveals a genomic signature distinct from that of embryonal rhabdomyosarcoma. Genes Chromosomes Cancer 63:e23238. https://doi.org/10.1002/gcc.23238CrossRefPubMed

95.

Stewart E, McEvoy J, Wang H, Chen X, Honnell V, Ocarz M, Gordon B, Dapper J, Blankenship K, Yang Y, Li Y, Shaw TI, Cho JH, Wang X, Xu B, Gupta P, Fan Y, Liu Y, Rusch M, Griffiths L, Jeon J, Freeman BB, 3rd, Clay MR, Pappo A, Easton J, Shurtleff S, Shelat A, Zhou X, Boggs K, Mulder H, Yergeau D, Bahrami A, Mardis ER, Wilson RK, Zhang J, Peng J, Downing JR, Dyer MA, St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome P (2018) Identification of therapeutic targets in rhabdomyosarcoma through integrated genomic, epigenomic, and proteomic analyses. Cancer Cell 34:411-426 e419. https://doi.org/10.1016/j.ccell.2018.07.012

96.

Klega K, Imamovic-Tuco A, Ha G, Clapp AN, Meyer S, Ward A, Clinton C, Nag A, Van Allen E, Mullen E, DuBois SG, Janeway K, Meyerson M, Thorner AR, Crompton BD (2018) Detection of somatic structural variants enables quantification and characterization of circulating tumor DNA in children with solid tumors. JCO Precis Oncol 2018. https://doi.org/10.1200/PO.17.00285

97.

Ruhen O, Lak NSM, Stutterheim J, Danielli SG, Chicard M, Iddir Y, Saint-Charles A, Di Paolo V, Tombolan L, Gatz SA, Aladowicz E, Proszek P, Jamal S, Stankunaite R, Hughes D, Carter P, Izquierdo E, Wasti A, Chisholm JC, George SL, Pace E, Chesler L, Aerts I, Pierron G, Zaidi S, Delattre O, Surdez D, Kelsey A, Hubank M, Bonvini P, Bisogno G, Di Giannatale A, Schleiermacher G, Schafer BW, Tytgat GAM, Shipley J (2022) Molecular characterization of circulating tumor DNA in pediatric rhabdomyosarcoma: a feasibility study JCO Precis. Oncol 6:e2100534. https://doi.org/10.1200/PO.21.00534CrossRef

98.

Abbou S, Klega K, Tsuji J, Tanhaemami M, Hall D, Barkauskas DA, Krailo MD, Cibulskis C, Nag A, Thorner AR, Pollock S, Imamovic-Tuco A, Shern JF, DuBois SG, Venkatramani R, Hawkins DS, Crompton BD (2023) Circulating tumor DNA is prognostic in intermediate-risk rhabdomyosarcoma: a report from the Children’s Oncology Group. J Clin Oncol 41:2382–2393. https://doi.org/10.1200/JCO.22.00409CrossRefPubMedPubMedCentral

99.

Frankel AO, Lathara M, Shaw CY, Wogmon O, Jackson JM, Clark MM, Eshraghi N, Keenen SE, Woods AD, Purohit R, Ishi Y, Moran N, Eguchi M, Ahmed FUA, Khan S, Ioannou M, Perivoliotis K, Li P, Zhou H, Alkhaledi A, Davis EJ, Galipeau D, Randall RL, Wozniak A, Schoffski P, Lee CJ, Huang PH, Jones RL, Rubin BP, Darrow M, Srinivasa G, Rudzinski ER, Chen S, Berlow NE, Keller C (2022) Machine learning for rhabdomyosarcoma histopathology. Mod Pathol 35:1193–1203. https://doi.org/10.1038/s41379-022-01075-xCrossRefPubMed

100.

Zhang X, Wang S, Rudzinski ER, Agarwal S, Rong R, Barkauskas DA, Daescu O, Furman Cline L, Venkatramani R, Xie Y, Xiao G, Leavey P (2022) Deep learning of rhabdomyosarcoma pathology images for classification and survival outcome prediction. Am J Pathol 192:917–925. https://doi.org/10.1016/j.ajpath.2022.03.011CrossRefPubMedPubMedCentral

101.

Milewski D, Jung H, Brown GT, Liu Y, Somerville B, Lisle C, Ladanyi M, Rudzinski ER, Choo-Wosoba H, Barkauskas DA, Lo T, Hall D, Linardic CM, Wei JS, Chou HC, Skapek SX, Venkatramani R, Bode PK, Steinberg SM, Zaki G, Kuznetsov IB, Hawkins DS, Shern JF, Collins J, Khan J (2023) Predicting molecular subtype and survival of rhabdomyosarcoma patients using deep learning of H&E images: a report from the Children’s Oncology Group. Clin Cancer Res 29:364–378. https://doi.org/10.1158/1078-0432.CCR-22-1663CrossRefPubMed

Title: Rhabdomyosarcoma in children and young adults
Authors: Sonja Chen
Anna M. Kelsey
Erin R. Rudzinski
Publication date: 18-12-2024
Publisher: Springer Berlin Heidelberg
Keyword: Rhabdomyosarcoma
Published in: Virchows Archiv / Issue 1/2025
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-024-03961-y

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