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

Chimene Kesserwan, 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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)762-769.e1
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Dermatofibrosarcoma
Severe Combined Immunodeficiency
Adenosine Deaminase
Proto-Oncogene Proteins c-sis
Cytogenetic Analysis
Fluorescence In Situ Hybridization
Skin
sis Genes
Neoplasms
Polymerase Chain Reaction
Genetic Translocation
Platelet-Derived Growth Factor
DNA Repair
Severe combined immunodeficiency due to adenosine deaminase deficiency
Extremities
Biopsy

Keywords

  • Severe combined immunodeficiency
  • adenosine
  • adenosine deaminase
  • dermatofibrosarcoma
  • fibrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kesserwan, C., Sokolic, R., Cowen, E. W., Garabedian, E., Heselmeyer-Haddad, K., Lee, C. C. R., ... Candotti, F. (2012). Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. Journal of Allergy and Clinical Immunology, 129(3), 762-769.e1. https://doi.org/10.1016/j.jaci.2011.10.028

Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. / Kesserwan, Chimene; Sokolic, Robert; Cowen, Edward W.; Garabedian, Elizabeth; Heselmeyer-Haddad, Kerstin; Lee, Chyi Chia Richard; Pittaluga, Stefania; Ortiz, Clarymar; Baird, Kristin; Lopez-Terrada, Dolores; Bridge, Julia; Wayne, Alan S.; Candotti, Fabio.

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 3, 03.2012, p. 762-769.e1.

Research output: Contribution to journalArticle

Kesserwan, C, Sokolic, R, Cowen, EW, Garabedian, E, Heselmeyer-Haddad, K, Lee, CCR, Pittaluga, S, Ortiz, C, Baird, K, Lopez-Terrada, D, Bridge, J, Wayne, AS & Candotti, F 2012, 'Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency', Journal of Allergy and Clinical Immunology, vol. 129, no. 3, pp. 762-769.e1. https://doi.org/10.1016/j.jaci.2011.10.028
Kesserwan, Chimene ; Sokolic, Robert ; Cowen, Edward W. ; Garabedian, Elizabeth ; Heselmeyer-Haddad, Kerstin ; Lee, Chyi Chia Richard ; Pittaluga, Stefania ; Ortiz, Clarymar ; Baird, Kristin ; Lopez-Terrada, Dolores ; Bridge, Julia ; Wayne, Alan S. ; Candotti, Fabio. / Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 129, No. 3. pp. 762-769.e1.
@article{fe47bee12ceb48a0af747279eb1b080a,
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.",
keywords = "Severe combined immunodeficiency, adenosine, adenosine deaminase, dermatofibrosarcoma, fibrosis",
author = "Chimene Kesserwan and Robert Sokolic and Cowen, {Edward W.} and Elizabeth Garabedian and Kerstin Heselmeyer-Haddad and Lee, {Chyi Chia Richard} and Stefania Pittaluga and Clarymar Ortiz and Kristin Baird and Dolores Lopez-Terrada and Julia Bridge and Wayne, {Alan S.} and Fabio Candotti",
year = "2012",
month = "3",
doi = "10.1016/j.jaci.2011.10.028",
language = "English (US)",
volume = "129",
pages = "762--769.e1",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency

AU - Kesserwan, Chimene

AU - Sokolic, Robert

AU - Cowen, Edward W.

AU - Garabedian, Elizabeth

AU - Heselmeyer-Haddad, Kerstin

AU - Lee, Chyi Chia Richard

AU - Pittaluga, Stefania

AU - Ortiz, Clarymar

AU - Baird, Kristin

AU - Lopez-Terrada, Dolores

AU - Bridge, Julia

AU - Wayne, Alan S.

AU - Candotti, Fabio

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Severe combined immunodeficiency

KW - adenosine

KW - adenosine deaminase

KW - dermatofibrosarcoma

KW - fibrosis

UR - http://www.scopus.com/inward/record.url?scp=84857800558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857800558&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2011.10.028

DO - 10.1016/j.jaci.2011.10.028

M3 - Article

C2 - 22153773

AN - SCOPUS:84857800558

VL - 129

SP - 762-769.e1

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -