| Disease | Neoplasm of the deep dermis with extension to the subcutis, characterized by locally aggressive growth. Dermatofibrosarcoma Protuberans (DFSP) is primarily associated with the trunk, limbs, head, neck and vulva. |
| Epidemiology | Rare soft tissue tumor, accounts for up to 1% of all soft tissue sarcomas. |
| Clinics | Typically diagnosed in young to middle-aged adults and affects either sex and all races, however numerous pediatric and congential cases have been reported. The duration of the lesions prior to diagnosis is commonly more than 5 years, and decades in some cases. |
| Pathology | Monotonous storiform pattern of uniform, cytologically bland spindle cells, with a characteristic honeycomb pattern of infiltration into the subcutaneous fat. Immunohistochemical staining demonstrates strong positivity for vimentin and CD34 and negativity for factor XIIIa staining. Apolipoprotein has also been described as a marker for DFSP. |
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| From top to bottom: a) Typical dermatofibrosarcoma protuberans (H&E, 40x), b) Strong CD34 immunoreactivity (CD34, 40x). |
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| Treatment | Preferred treatment for DFSP is wide surgical excision with pathologically negative margins. Recently Imatinib mesylate therapy has been documented to induce extensive regression of primary and metastatic lesions. |
| Prognosis | Despite the local invasiveness, DFSP rarely metastasizes. The risk for development of metastatic disease is only 5%. The extent of surgical excision determines the prognosis of the patient. To reduce the local recurrence rate, a wide surgical excision with adequate margins is used. |
Cytogenetics
Morphological | Cytogenetically, DFSP is characterized by the presence of the recurrent t(17;22)(q22;q13) translocation or, more commonly, supernumerary ring chromosomes containing material from chromosomal regions 17q22 and 22q13 accompanied by simple chromosome trisomies. The translocation results in the fusion of the alpha chain type 1 of collagen (COL1A1) gene with the platelet-derived growth factor Beta (PDGFbeta) gene. |
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| der(22)t(17;22)(q21;q13) in dermatofibrosarcoma protuberans, G-banding; - Courtesy Lisa Biazo and Charles D. Bangs |
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| Cytogenetics Molecular | Fluorescence in situ hybridization based approaches can be used to demonstrate the t(17;22), using gene specific probes to demonstrate PDGFbeta gene rearrangements as well as genetic gains and losses. |
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| FISH of a DFSP case using a break-apart probe to the PDGFB locus shows tumor cells with one yellow signal indicating an intact PDGFB locus, and two or more green signals, representing additional copies of an unbalanced rearranged PDGFB locus (x100). |
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| Gene Name | COL1A1 (collagen, type I, alpha 1) |
| Location | 17q21.33 |
| Note | Molecular Location: From base pairs 45,616,456 to 45,633,999. |
| Dna / Rna | COL1A1 is transcribed from centromere to telomere at 17q21.31-q22. The mRNA sequence contains 5927bp, comprising 52 exons and spans approximately 18kb. Exons 5 to 49 encode the alpha helical domain. |
| Protein | The COL1A1 gene produces a component of type I collagen called the pro-a1(I) chain. The Alpha1 (I) chains of the type I collagen are synthesized as procollagen molecules containing amino and carboxy-terminal propeptides, which are removed by site-specific endopeptidase synthesizing the 1464 amino acid protein. |
| Mesenchymal Tumors |
| Fletcher C, |
| Diagnostic Histopathology of Tumors. 2007; Churchill Livingstone 3rd Ed.; vol 2: 1489-1491. |
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| Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. |
| McArthur GA, Demetri GD, van Oosterom A, Heinrich MC, Debiec-Rychter M, Corless CL, Nikolova Z, Dimitrijevic S, Fletcher JA. |
| J Clin Oncol. 2005; 23: 866-873. |
| PMID 15681532 |
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| Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. |
| Naeem R, Lux ML, Huang SF, Naber SP, Corson JM, Fletcher JA. |
| Am J Pathol. 1995; 147: 1553-1558. |
| PMID 7495279 |
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| Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberan cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. |
| Patel KU, Szabo SS, Hernandez VS, Prieto VG, Abruzzo LV, Lazar AJ, Lopez-Terrada D. |
| Human Pathology. 2008; 39: 184-193. |
| PMID 17950782 |
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| PDGFB. |
| Simon MP, Maire G, and Pedeutour F. |
| Atlas Genet Cytogenet Oncol Haematol. February 2001. |
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| Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. |
| West RB, Harvell J, Linn SC, Liu CL, Prapong W, Hernandez-Boussard T, Montgomery K, Nielsen TO, Rubin BP, Patel R, Goldblum JR, Brown PO, van de Rijn M. |
| Am J Surg Pathol. 2004; 2 : 1063-1069. |
| PMID 15252314 |
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