title: Ewing family of tumours involving the vulva and vagina: report of a series of four cases.
abstract: BACKGROUND
  Ewing's sarcoma and peripheral primitive neuroectodermal tumour (pPNET) are now regarded as two morphological ends of a spectrum of neoplasms, characterised by a t(11;22) or other related chromosomal translocation involving the EWS gene on chromosome 22 and referred to as Ewing family of tumours (EFTs). EFTs are extremely rare in the vulva and vagina, a review of the literature revealing only 13 previously reported possible cases, most of which have not had molecular confirmation. In this study, four new cases of EFTs involving the vulva (three cases) or vagina (one case) are reported.
  
  
  RESULTS
  The tumours occurred in women aged 19, 20, 30 and 40 years and ranged in size from 3 to 8 cm. Morphologically, all neoplasms had a lobulated architecture and were composed of solid aggregates of cells. In one case, occasional rosettes were formed. In all the tumours, there was diffuse membranous staining with CD99; nuclear positivity with FLI-1 was present in two cases. Three cases were focally positive with the broad-spectrum cytokeratin AE1/3, all were diffusely positive with vimentin and all were desmin negative. In two cases, a t(11;22) (q24;q12) (EWSR1-FLI-1) chromosomal translocation was demonstrated by reverse transcriptase-PCR (one case) and fluorescence in situ hybridisation (FISH) (one case), and in another case a rearrangement of the EWSR1 gene on chromosome 22 was demonstrated by FISH. In the other case, a variety of molecular studies did not reveal a translocation involving the EWS gene but this tumour, on the balance of probability, is still considered to represent a neoplasm in the EFTs. Follow-up in two cases revealed that one patient developed pulmonary metastasis and died and another is alive without disease at 12 months.
  
  
  CONCLUSIONS
  This report expands the published literature regarding EFTs involving the vulva and vagina and stresses the importance of molecular techniques in firmly establishing the diagnosis, especially when these neoplasms arise at unusual sites.
authors.affiliation: Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland. glenn.mccluggage@bll.n-i.nhs.uk
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Vaiyapuri P
authors.initials: VP
authors.lastname: Sumathi
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: Michelle
authors.initials: M
authors.lastname: Hirsch
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Michael
authors.initials: M
authors.lastname: Wells
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
mesh_terms: D000071443:12E7 Antigen; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators; D014178:Translocation, Genetic; D014625:Vaginal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; C098179:FLII protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators