title: Primary cutaneous and subcutaneous Ewing sarcoma.
abstract: BACKGROUND
  Primary cutaneous/subcutaneous Ewing sarcoma (scEWS) is extremely rare. We describe clinical features, treatment, and outcome of this Ewing localization.
  
  
  METHODS
  Retrospective study (1996-2012) on 56 patients.
  
  
  RESULTS
  Most primary scEWS occurred in late adolescent/young adult females (F/M = 1.9; median age 21.5 years), with primary tumor in the extremity/trunk (48.5%/39%). Only 35/56 samples had Real-Time-Polymerase-Chain-Reaction/Fluorescent-In-Situ-Hybridization analysis, 32/35 had EWS-translocation. Most of them exhibited known favorable prognostic factors: localized disease (54/56), initial tumor volume < 200 ml (51/53). Thirty and 25 patients received chemotherapy according to Euro-Ewing99 or a shorter/less intense chemotherapy regimen associated with milder toxicity. One patient had not received chemotherapy. Surgery was performed at diagnosis in 37 patients (18/37 marginal/intra-lesional resections) followed by secondary surgery in 8/37 (three remained marginal). Nineteen other patients had an initial biopsy followed by chemotherapy, 15/19 underwent late surgery (4/15 marginal/intra-lesional resections). Overall, 27/56 patients received radiotherapy. Median follow-up was six years (1-15). Two patients with metastatic disease progressed at metastatic sites. Four patients with localized disease experienced progression/relapse (local n = 3, metastatic n = 1). Survival was excellent: 5y-OS and 5y-EFS were 93.8% (95%CI = 83-98%) and 88.5% (95%CI-= 77-95), respectively.
  
  
  CONCLUSIONS
  Unplanned primary surgery should be avoided to try to minimize potential long term sequels due to secondary surgery or radiotherapy. Biopsy with molecular analysis and staging should be performed at diagnosis to inform treatment recommendations. Patients with metastases should be treated aggressively as for other metastatic EWS. Further studies are necessary to clarify whether a less intensive chemotherapy regimen could be safely used in localized disease to minimize acute/late toxicities.
authors.affiliation: MD, Pediatric and Adolescent Oncology, Gustave Roussy, 114 Rue Eduard Vaillant, 94805, Villejuif, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Di Giannatale
authors.affiliation: MD, Royal Marsden Fulham Road, SW3 6JJ,, London, UK.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.affiliation: Biostatistics Department, Institut Gustave Roussy, Paris-Sud University, 114 Rue Eduard Vaillant, 94805, Villejuif, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Pediatric Onco-Hematology Institute, Centre Léon Bérard, 28 Rue Laennec, 69008, Lyon, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Bérard
authors.affiliation: MD, Royal Marsden Fulham Road, SW3 6JJ,, London, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Benson
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, 69008, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Department of Medical Oncology, Institut Bergonie, 229 cours de l'Argonne, 33076, Bordeaux Cedex, France.
authors.forename: Binh
authors.initials: B
authors.lastname: Bui
authors.affiliation: MD, Royal Marsden Fulham Road, SW3 6JJ,, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Judson
authors.affiliation: MD, Pediatric and Adolescent Oncology, Gustave Roussy, 114 Rue Eduard Vaillant, 94805, Villejuif, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: University College Hospital London NHS Foundation Trust, 1st Floor Central, 250 Euston Road, London, NW1 2PG, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Whelan
authors.affiliation: MD, Pediatric and Adolescent Oncology, Gustave Roussy, 114 Rue Eduard Vaillant, 94805, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaspar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012086:Reoperation; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D012878:Skin Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D040521:Subcutaneous Tissue / Q000473:pathology; D014178:Translocation, Genetic; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
keywords: adolescent; cutaneous; ewing sarcoma; subcutaneous; young adults