Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency

J Allergy Clin Immunol. 2012 Mar;129(3):762-769.e1. doi: 10.1016/j.jaci.2011.10.028. Epub 2011 Dec 6.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Deaminase / genetics
  • Adolescent
  • Adult
  • Antigens, CD34 / metabolism
  • Child
  • Chromosomes, Human, Pair 22 / genetics
  • DNA Repair-Deficiency Disorders
  • Dermatofibrosarcoma / complications*
  • Dermatofibrosarcoma / diagnosis
  • Dermatofibrosarcoma / genetics
  • Dermatofibrosarcoma / pathology
  • Early Detection of Cancer
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Severe Combined Immunodeficiency / complications*
  • Severe Combined Immunodeficiency / diagnosis
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / pathology
  • Skin Neoplasms / complications*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Translocation, Genetic


  • Antigens, CD34
  • COLIA1-PDGFB fusion protein, human
  • Oncogene Proteins, Fusion
  • Adenosine Deaminase