Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Annals of Surgical Oncology
Erschienen in: Annals of Surgical Oncology 10/2007

01.10.2007 | Bone and Soft Tissue Sarcomas

Dermatofibrosarcoma Protuberans: Recent Clinical Progress

verfasst von: Grant McArthur, MBBS, BMedSc, PhD, FRACP

Erschienen in: Annals of Surgical Oncology | Ausgabe 10/2007

Einloggen, um Zugang zu erhalten

Abstract

Background

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor of low malignant grade characterized by a pattern of slow, infiltrative growth and a marked tendency to recur locally after surgical excision. Wide surgical resection is generally accepted as optimal treatment for DFSP. However, despite optimal surgical management, distant metastases may develop in up to 5% of patients. More than 90% of DFSP are characterized by a reciprocal chromosomal translocation, t(17;22). This rearrangement leads to constitutive activation of the platelet-derived growth factor receptor (PDGFR) as a result of deregulated ligand expression, thus providing a rationale for targeted inhibition of PDGFR as a treatment strategy for patients with unresectable locally advanced or metastatic DFSP.

Methods

This article reviews the current understanding of DFSP, with emphasis on molecular-level pathogenetic events and their implications for management, and evidence for the role of tyrosine kinase inhibition in improving the outcomes of patients with unresectable locally advanced or metastatic DFSP.

Results

Surgery with wide margins remains the cornerstone in the management of DFSP. Recently, imatinib, a potent, selective inhibitor of the PDGFR alpha and PDGFR beta protein-tyrosine kinases, has been reported to induce complete or partial remissions in most patients treated for advanced DFSP.

Conclusions

Imatinib is approved for treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP who are not eligible for surgery. Future investigations will determine whether imatinib can also be used in the neoadjuvant setting to reduce tumor volume, thereby allowing resection of very large DFSP that would otherwise not be resectable.
Literatur
1.
Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol 2004;30:341–5PubMedCrossRef
2.
3.
Fiore M, Miceli R, Mussi C, et al. Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate. J Clin Oncol 2005;23:7669–75PubMedCrossRef
4.
Gloster HM, Jr., Harris KR, Roenigk RK. A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996;35:82–7PubMedCrossRef
5.
Mendenhall WM, Zlotecki RA, Scarborough MT. Dermatofibrosarcoma protuberans. Cancer 2004;101:2503–8PubMedCrossRef
6.
Szollosi Z, Nemes Z. Transformed dermatofibrosarcoma protuberans: a clinicopathological study of eight cases. J Clin Pathol 2005;58:751–6PubMedCrossRef
7.
Wacker J, Khan-Durani B, Hartschuh W. Modified Mohs micrographic surgery in the therapy of dermatofibrosarcoma protuberans: analysis of 22 patients. Ann Surg Oncol 2004;11:438–44PubMedCrossRef
8.
Snow SN, Gordon EM, Larson PO, Bagheri MM, Bentz ML, Sable DB. Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature. Cancer 2004;101:28–38PubMedCrossRef
9.
Bowne WB, Antonescu CR, Leung DH, et al. Dermatofibrosarcoma protuberans: a clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000;88:2711–20PubMedCrossRef
10.
Nakra T, Cook T, Douglas RS, Goldberg RA. Dermatofibrosarcoma protuberans metastatic to the orbit. Arch Ophthalmol 2004;122:1240–1PubMedCrossRef
11.
Yokoyama Y, Murakami Y, Sasaki M, et al. Pancreatic metastasis of dermatofibrosarcoma protuberans. J Gastroenterol 2004;39:798–800PubMedCrossRef
12.
Shimizu A, O’Brien KP, Sjoblom T, et al. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 1999;59:3719–23PubMed
13.
Sjoblom T, Shimizu A, O’Brien KP, et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 2001;61:5778–83PubMed
14.
McArthur GA, Demetri GD, van Oosterom A, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol 2005;23:866–73PubMedCrossRef
15.
Greco A, Roccato E, Miranda C, Cleris L, Formelli F, Pierotti MA. Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer 2001;92:354–60PubMedCrossRef
16.
Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 1996;56:100–4PubMed
17.
Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000;295:139–45PubMed
18.
Dewar AL, Cambareri AC, Zannettino AC, et al. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood 2005;105:3127–32PubMedCrossRef
19.
Okuda K, Weisberg E, Gilliland DG, Griffin JD. ARG tyrosine kinase activity is inhibited by STI571. Blood 2001;97:2440–8PubMedCrossRef
20.
Maki RG, Awan RA, Dixon RH, Jhanwar S, Antonescu CR. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer 2002;100:623–6PubMedCrossRef
21.
McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol 2004;31(2 Suppl 6):30–6PubMedCrossRef
22.
Rubin BP, Schuetze SM, Eary JF, et al. Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol 2002;20:3586–91PubMedCrossRef
23.
Labropoulos SV, Fletcher JA, Oliveira AM, Papadopoulos S, Razis ED. Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs 2005;16:461–6PubMedCrossRef
24.
Naeem R, Lux ML, Huang SF, Naber SP, Corson JM, Fletcher JA. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol 1995;147:1553–8PubMed
25.
Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Dermatofibrosarcoma protuberans and giant cell fibroblastoma. Cancer Genet Cytogenet 2003;140:1–12PubMedCrossRef
26.
Simon MP, Pedeutour F, Sirvent N, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 1997;15:95–8PubMedCrossRef
27.
Heldin CH, Ostman A, Ronnstrand L. Signal transduction via platelet-derived growth factor receptors. Biochim Biophys Acta 1998;1378:F79–113PubMed
28.
O’Brien KP, Seroussi E, Dal Cin P, et al. Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas. Genes Chromosomes Cancer 1998;23:187–93PubMedCrossRef
29.
Wang J, Hisaoka M, Shimajiri S, Morimitsu Y, Hashimoto H. Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues. Diagn Mol Pathol 1999;8:113–9PubMedCrossRef
30.
Greco A, Fusetti L, Villa R, et al. Transforming activity of the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor b-chain gene in dermatofibrosarcoma protuberans. Oncogene 1998;17:1313–9PubMedCrossRef
31.
Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD. Fibrosarcomatous (“high-grade”) dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998;22:576–87PubMedCrossRef
32.
Stojadinovic A, Karpoff HM, Antonescu CR, et al. Dermatofibrosarcoma protuberans of the head and neck. Ann Surg Oncol 2000;7:696–704PubMedCrossRef
33.
Martin L, Piette F, Blanc P, et al. Clinical variants of the preprotuberant stage of dermatofibrosarcoma protuberans. Br J Dermatol 2005;153:932–6PubMedCrossRef
34.
West RB, Harvell J, Linn SC, et al. Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol 2004;28:1063–9PubMedCrossRef
35.
Ramakrishnan VSA, Ehrlich M, Powell S, Lucci A Jr. Atypical dermatofibrosarcoma protuberans in the breast. Breast J 2005;11:217–8PubMedCrossRef
36.
Mizutani K, Tamada Y, Hara K, et al. Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans. Br J Dermatol 2004;151:235–7PubMedCrossRef
37.
McArthur GA. Dermatofibrosarcoma protuberans: a surgical disease with a molecular savior. Curr Opin Oncol 2006;18:341–6PubMedCrossRef
38.
Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol 1992;18:241–8PubMed
39.
Khatri VP, Galante JM, Bold RJ, Schneider PD, Ramsamooj R, Goodnight JE, Jr. Dermatofibrosarcoma protuberans: reappraisal of wide local excision and impact of inadequate initial treatment. Ann Surg Oncol 2003;10:1118–22PubMedCrossRef
40.
41.
Nouri K, Lodha R, Jimenez G, Robins P. Mohs micrographic surgery for dermatofibrosarcoma protuberans: University of Miami and NYU experience. Dermatol Surg 2002;28:1060–4PubMedCrossRef
42.
Massey RA, Tok J, Strippoli BA, Szabolcs MJ, Silvers DN, Eliezri YD. A comparison of frozen and paraffin sections in dermatofibrosarcoma protuberans. Dermatol Surg 1998;24:995–8PubMedCrossRef
43.
Garcia C, Viehman G, Hitchcock M, Clark RE. Dermatofibrosarcoma protuberans treated with Mohs surgery. A case with CD34 immunostaining variability. Dermatol Surg 1996;22:177–9PubMedCrossRef
44.
National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Dermatofibrosarcome protuberans. Version 1.2006. Available at http://​www.​nccn.​org/professionals/physicians_gls/PDF/dfsp.pdf. Accessed July 27, 2006
45.
Suit H, Spiro I, Mankin HJ, Efird J, Rosenberg AE. Radiation in management of patients with dermatofibrosarcoma protuberans. J Clin Oncol 1996;14:2365–9PubMed
46.
Ballo MT, Zagars GK, Pisters P, Pollack A. The role of radiation therapy in the management of dermatofibrosarcoma protuberans. Int J Radiat Oncol Biol Phys 1998;40:823–7PubMedCrossRef
47.
Dagan R, Morris CG, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 2005;28:537–9PubMedCrossRef
48.
Lindner NJ, Scarborough MT, Powell GJ, Spanier S, Enneking WF. Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities. Eur J Surg Oncol 1999;25:392–7PubMedCrossRef
49.
Price V, Zielenska M, Smith C, Chilton-Macneill S, Malkin D, Pappo A. Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs) [abstract]. Proc Am Soc Clin Oncol 2004;23:804
50.
Price VE, Fletcher JA, Zielenska M, et al. Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer 2005;44:511–5PubMedCrossRef
51.
Corless CL, Heinrich MC, Dimitrijevic S, et al. Correlation of imatinib response with activation of KIT and PDGF receptors in a variety of cancers: results of the CSTIB2225 trial [abstract]. Proc Am Soc Clin Oncol 2003;22:783
52.
van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 2001;358:1421–3PubMedCrossRef
53.
Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472–80PubMedCrossRef
54.
Imatinib in dermatofibrosarcoma protuberans (DFSP): sponsored by Dermatologic Cooperative Oncology Group. ClinicalTrials.gov identifier: NCT00122473
55.
Neoadjuvant imatinib in dermatofibrosarcoma protuberans: sponsored by Sarcoma Alliance for Research Through Collaboration. ClinicalTrials.gov identifier: NCT00243191
56.
A short course of neoadjuvant Gleevec (imatinib mesylate) in dermatofibrosarcoma protuberans: sponsored by University of Michigan Cancer Center. ClinicalTrials.gov identifier: NCT00176709
57.
Imatinib mesylate in treating patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblasoma: sponsored by European Organization for Research and Treatment of Cancer. ClinicalTrials.gov identifier: NCT00085475
58.
Imatinib mesylate in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP: sponsored by Southwest Oncology Group and National Cancer Institute. ClinicalTrials.gov identifier: NCT00084630
Metadaten
Titel
Dermatofibrosarcoma Protuberans: Recent Clinical Progress
verfasst von
Grant McArthur, MBBS, BMedSc, PhD, FRACP
Publikationsdatum
01.10.2007
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 10/2007
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9480-y

Weitere Artikel der Ausgabe 10/2007

Annals of Surgical Oncology 10/2007 Zur Ausgabe

Breast Oncology

Clinicopathologic Features and Long-Term Outcomes of 293 Phyllodes Tumors of the Breast

Thoracic Oncology

Limited Cardiotoxicity after Extensive Thoracic Surgery and Intraoperative Hyperthermic Intrathoracic Chemotherapy with Doxorubicin and Cisplatin

Breast Oncology

Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation

Gastrointestinal Oncology

Young Age Influences Treatment but not Outcome of Colon Cancer

ReviewPaper

Talc Pleurodesis for Malignant Pleural Effusions Is Preferred Over the Pleurx Catheter (Contrary Position)

Bone and Soft Tissue Sarcomas

Post Operative Infection and Increased Survival in Osteosarcoma Patients: Are They Associated?

Neu im Fachgebiet Chirurgie

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.
Bildnachweise