title: Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency.
abstract: BACKGROUND
  Dermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor associated with a characteristic chromosomal translocation (t[17;22][q22;q13]) resulting in the COL1A1-platelet-derived growth factor β(PDGFB) fusion gene. This malignancy is rarely diagnosed in childhood.
  
  
  OBJECTIVE
  We observed an unexpected high incidence of this DFSP in children affected with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) and set out to evaluate the association of these 2 clinical entities.
  
  
  METHODS
  Twelve patients with ADA-SCID were evaluated with a complete dermatologic examination and skin biopsy when indicated. Conventional cytogenetic and molecular analyses (fluorescence in situ hybridization, RT-PCR, or both) were performed when possible.
  
  
  RESULTS
  Eight patients were found to have DFSP. Six patients had multicentric involvement (4-15 lesions), primarily of the trunk and extremities. Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions were present in 3 patients. In all cases CD34 expression was diffusely positive, and diagnosis was confirmed either by means of cytogenetic analysis, molecular testing, or both. The characteristic DFSP-associated translocation, t(17;22)(q22;q13), was identified in 6 patients; results of fluorescence in situ hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7 patients; and RT-PCR showed the COL1A1-PDGFB fusion transcript in 6 patients.
  
  
  CONCLUSIONS
  We describe a previously unrecognized association between ADA-SCID and DFSP with unique features, such as multicentricity and occurrence in early age. We hypothesize that the t(17;22)(q22;q13) translocation that results in dermal overexpression of PDGFB and favors the development of fibrotic tumors might arise because of the known DNA repair defect in patients with ADA-SCID. Although the natural course of DFSP in the setting of ADA-SCID is unknown, this observation should prompt regular screening for DFSP in patients with ADA-SCID.
authors.affiliation: Genetics and Molecular Biology Branch and the Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4442, USA.
authors.forename: Chimene
authors.initials: C
authors.lastname: Kesserwan
authors.forename: Robert
authors.initials: R
authors.lastname: Sokolic
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garabedian
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heselmeyer-Haddad
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Clarymar
authors.initials: C
authors.lastname: Ortiz
authors.forename: Kristin
authors.initials: K
authors.lastname: Baird
authors.forename: Dolores
authors.initials: D
authors.lastname: Lopez-Terrada
authors.forename: Julia
authors.initials: J
authors.lastname: Bridge
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D049914:DNA Repair-Deficiency Disorders; D018223:Dermatofibrosarcoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D012878:Skin Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D018952:Antigens, CD34; C120892:COLIA1-PDGFB fusion protein, human; D015514:Oncogene Proteins, Fusion; D000243:Adenosine Deaminase