Response of malignant scalp dermatofibrosarcoma to presurgical targeted growth factor inhibition

Case report

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Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive, malignant cutaneous tumor that sparingly presents on the scalp. Dermatofibrosarcomas often result from the formation of a fusion oncogene on translocated or supernumerary ring chromosomes 17 and 22, causing the overexpression of PDGFRβ driven by the COL1A1 promoter. Because of uncertainty surrounding appropriate treatment of aggressive scalp DFSP, the authors performed an extensive review of the available data from a MEDLINE (Ovid) search to describe the clinical presentation and treatment options for this rare tumor. Their search identified 39 different cases, including the illustrative case presented in this study.

Adjuvant therapy for this malignant lesion is not universally established in the literature. In the present case, the authors successfully treated a locally invasive scalp DFSP with presurgical therapy that specifically inhibited the PDGFβ receptor. Imatinib significantly shrank the DFSP tumor mass, reduced hypervascularity, reduced metabolic activity on PET scanning, and permitted a safe gross-total resection. Although wide excision and Mohs micrographic surgery remain the standard surgical treatments for DFSP, the authors illustrate that presurgical chemotherapeutic treatment by imatinib provides a critical adjunct to traditional therapy.

Abbreviations used in this paper:ATP = adenosine triphosphate; DFSP = dermatofibrosarcoma protuberans; FISH = fluorescence in situ hybridization; GTR = gross-total resection; MMS = Mohs micrographic surgery; PDGF = platelet-derived growth factor; PDGFRβ = PDGF receptor–β; PFS = progression-free survival; RT = radiation therapy; STSG = split-thickness skin graft.

Article Information

Address correspondence to: D. Cory Adamson, M.D., Ph.D., Duke University Medical Center, Box 2624, Durham, North Carolina 27710. email: cory.adamson@duke.edu.

Please include this information when citing this paper: published online August 14, 2009; DOI:10.3171/2009.7.JNS09522.

© AANS, except where prohibited by US copyright law.

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Figures

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    Coronal T1-weighted, Gd-enhanced MR image showing a round, 6-cm, homogenously enhancing, well-circumscribed mass invading through the left occipital scalp and underlying dura. A sagittal T1-weighted, Gd-enhanced image confirmed intracranial invasion with tumor adjacent to transverse sinus (not shown); the lesion was homogeneously isointense on T2-weighted images, and hypointense on noncontrast-enhanced T1-weighted images (not shown).

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    Cytogenetic analysis of scalp DFSP karyotype revealing classic chromosome 17 and 22 ring configuration (left), and FISH (right) showing colocalization of PDGFβ; and COL1A1 promoter. Tissue analysis revealed 2 related abnormal clones: a near-diploid clone and a near-tetraploid clone that appeared to reflect a doubling product of the near-diploid clone. A ring chromosome and marker chromosomes with banding character consistent with portions of the long arm of chromosomes 17 and 22 were present in the near-diploid (shown) and the near-tetraploid clones. Note the loss of 22 and abnormal banding of 17 in near-diploid clone. The detailed karyotype of both clones was 44–48, XY, del(7)(p21), del(9)(p21), add(15)(p11.2),–18,–22,+1–2mar, +r[cp5]/89–92,idemx2[5]. The FISH shows colocalization (yellow) of the PDGFβ gene (green probe) and COL1A1 promoter (red probe). Nuclei are blue (stained with DAPI).

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    Photograph of the occipital scalp DFSP after treatment with imatinib. The patient presented with a 6-cm, friable, left occipital scalp mass that frequently hemorrhaged, requiring multiple tight bandages for hemostasis. After biopsy for cytogenetic analysis and treatment with imatinib, the tumor markedly shrank to a 3-cm, firm, and much less hemorrhagic mass, seen here. Note the retraction of skin around the inferior edge after shrinkage.

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    Photomicrographs demonstrating histological characteristics consistent with DFSP. Left: Spindle cell tumor characterized by intersecting fascicles in a storiform pattern. H & E, original magnification × 20. Right: Staining for CD34 highlights the tumor cells and blood vessels. Original magnification × 40.

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    Graph showing PFS after treatment of scalp DFSP. Median PFS was 24 months. In 2 cases diffuse metastases to brain, lung, and liver were reported at the time of progression.

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    Imatinib mechanism of action in PDGF signaling cascade. Phosphorylation sites downregulated by imatinib: Akt, BCRABL, CKII, CSK, DOK1, ERK, GRB2, GSK3, MAPK1, MEK, mTOR, P38, PDGF, PI3K, PKC, PLCγ. RAF/RAS, RasGAP, RSK2, RSK3, and SRC.

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    Flow chart of the scalp DFSP treatment algorithm.

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