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.

FIG 1

Clinical presentation of DFSP in patients with ADA-SCID. A, Flat plaque (ADA12). B, Depressed plaque (ADA7). C, Slightly raised plaque (ADA1; see also Fig 2, B, E, and H). D, Subcutaneous nodule (ADA16; see also Fig 2, C, F, and I).

FIG 2

Histologic features of DFSP in patients with ADA-SCID. A and D, Low cellularity from a depressed plaque (ADA14). B and E, Storiform pattern from a raised plaque (ADA1). C and F, Vascular spindle cell lesion in a myxoid background with floret cells characteristic of GCF (ADA16). G-I, CD34 stain decorating spindle cells in all 3 lesions.

FIG 3

Molecular characteristics of DFSP in patients with ADA-SCID. A, Karyotyping from a lesion (ADA14) showing t(17;22)(q22;q13). B, FISH of a lesion (ADA16) revealing 2 fused red/green signals consistent with the presence of the COL1A1-PDGFB fusion. C, Sequence of the RT-PCR product from a lesion (ADA7) showing the junction of the COL1A1 and PDGFB transcripts.