Literature DB >> 22153773

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

Chimene Kesserwan1, Robert Sokolic, Edward W Cowen, Elizabeth Garabedian, Kerstin Heselmeyer-Haddad, Chyi-Chia Richard Lee, Stefania Pittaluga, Clarymar Ortiz, Kristin Baird, Dolores Lopez-Terrada, Julia Bridge, Alan S Wayne, Fabio Candotti.   

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. Published by Mosby, Inc.

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Year:  2011        PMID: 22153773      PMCID: PMC3294021          DOI: 10.1016/j.jaci.2011.10.028

Source DB:  PubMed          Journal:  J Allergy Clin Immunol        ISSN: 0091-6749            Impact factor:   10.793


  24 in total

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