Información del artículo
Abstract
Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate malignancy that is initially localized to the skin from where it can invade deep structures (fat, fascia, muscle and bone). It is the most frequent fibrohistiocytic tumor, comprising approximately 1.8% of all soft tissue sarcomas and 0.1% of all cancers. It has an estimated incidence of 0.8-5 cases per one million persons per year. Treatment of localized disease consists in complete surgical excision of the lesion by conventional surgery with wide margins (> 3cm) or by micrographic Mohs surgery. Although the cases of metastatic DFSP do not reach 5% of the total, almost all of them appear after previous local relapses. The prognosis for metastatic cases is very poor with a survival of less than 2 years following detection of metastatic disease. Patients with locally advanced DFSP are not candidates for an initial radical surgical therapy therefore neoadyuvant treatment is required prior to surgery in order to reduce tumor burden. In this regard, chemotherapy and radiotherapy have not been highly efficacious so it is necessary to consider new alternatives. The demonstration of the oncogenic power of the translocation COL1A1-PDGFB in DFSP has allowed the successful introduction of drug therapy with antagonists of the PDGFB receptor for metastatic or locally advanced cases.
Key words:
dermatofibrosarcoma protuberans
Mohs surgery
COL1A1-PDGFB
imatinib
RT-PCR
Resumen
El dermatofibrosarcoma protuberans (DFSP) es una neoplasia de partes blandas de malignidad intermedia, localizada inicialmente en la piel, desde donde invade tejidos más profundos (grasa, fascia, músculo y hueso). Se trata del tumor fibrohistiocitario más frecuente, constituyendo aproximadamente el 1,8% de todos los sarcomas de partes blandas y un 0,1% de todos los cánceres. Su incidencia se ha estimado entre 0,8-5 casos por millón de habitantes y año. El tratamiento de la enfermedad localizada consiste en la resección quirúrgica completa de la lesión, bien mediante cirugía convencional con margen amplio > 3cm) bien mediante cirugía micrográfica de Mohs. Aunque los casos de DFSP metastásico no llegan al 5% del total, prácticamente todos ellos aparecen tras recaídas locales previas. El pronóstico de los casos metastásicos es muy pobre, con menos de 2 años de supervivencia tras la detección de la enfermedad metastásica. Los pacientes de DFSP con tumores localmente avanzados no son susceptibles de tratamiento quirúrgico radical de inicio, por lo que se precisa tratamiento neoadyuvante previo a la cirugía para disminuir el tamaño tumoral. En este sentido, la quimioterapia y la radioterapia se han mostrado poco eficaces, por lo que se hace necesario contar con nuevas alternativas terapéuticas. La demostración del poder oncogénico de la traslocación COL1A1-PDGFB en el DFSP ha permitido introducir con éxito el tratamiento farmacológico con inhibidores del receptor del PDGFB en los casos metastáticos o localmente avanzados.
Palabras clave:
dermatofibrosarcoma protuberans
cirugía de Mohs
COL1A1-PDGFB
imatinib
TI-PCR
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References
[1.]
J. Darier, M. Ferrand.
Dermatofibromes progressifs et recidivants ou fibrosarcomes de la peau.
Ann Dermatol Syphiligr (Paris), 5 (1924), pp. 542-562
[2.]
E. Hoffman.
Ueber das knollentribende fibrosarkam der haut (dermatofibrosarcoma protuberans).
Dermatol Z, 43 (1925), pp. 1-28
[3.]
H.B. Taylor, E.B. Helwig.
Dermatofibrosarcoma protuberans. A study of 115 cases.
Cancer, 15 (1962), pp. 717-725
[4.]
D.A. Altman, B.J. Nickoloff, D.P. Fivenson.
Dermatofibrosarcoma protuberans strongly express CD34 (abstract).
J Cutan Pathol, 19 (1992), pp. 509
[5.]
P. Abenoza, T. Lillemoe.
CD34 and factor XIIIa in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans.
Am J Dermatopathol, 15 (1993), pp. 429-434
[6.]
M.P. Simon, F. Pedeutour, N. Sirvent, J. Grosgeorge, F. Minoletti, J.M. Coindre, et al.
Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giantcell fibroblastoma.
Nat Genet, 15 (1997), pp. 95-98
[7.]
B. Llombart, O. Sanmartín, J. López-Guerrero.
Dermatofibrosarcoma protuberante en la infancia.
Piel, 21 (2006), pp. 435-441
[8.]
K. Bendix-Hansen, O. Myhre-Jensen, S. Kaae.
Dermatofibrosarcoma protuberans. A clinico-pathological study of nineteen cases and review of world literature.
Scand J Plast Reconstr Surg, 17 (1983), pp. 247-252
[9.]
T.-Y.S.W. Chuang, S.A. Muller.
Incidence of cutaneous T cell lymphoma and other rare skin tumors in a defined population.
J Am Acad Dermatol, 23 (1990), pp. 254-256
[10.]
V.D. Criscione, M.A. Weinstock.
Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002.
J Am Acad Dermatol, (2006),
[11.]
H.M. Gloster Jr..
Dermatofibrosarcoma protuberans.
J Am Acad Dermatol, 35 (1996), pp. 355-374
[12.]
W.B. Dupree, J.M. Langloss, S.W. Weiss.
Pigmented dermatofibrosarcoma protuberans (Bednar tumor). A pathologic, ultrastructural, and immunohistochemical study.
Am J Surg Pathol, 9 (1985), pp. 630-639
[13.]
E.J. Rutgers, B.B. Kroon, C.E. Albus-Lutter, E. Gortzar.
Dermatofibrosarcoma protuberans: treatment and prognosis.
Eur J Surg Oncol, 18 (1992), pp. 241-248
[14.]
G. Annessi, A. Cimitan, G. Girolomoni, A. DiSilveiro.
Congenital dermatofibrosarcoma protuberans.
Pediatr Dermatol, 10 (1993), pp. 40-42
[15.]
P.H. McKee, C.D. Fletcher.
Dermatofibrosarcoma protuberans presenting in infancy and childhood.
J Cutan Pathol, 18 (1991), pp. 241-246
[16.]
S.R. Checketts, T.K. Hamilton, R.D. Baughman.
Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature.
J Am Acad Dermatol, 42 (2000), pp. 907-913
[17.]
L. Martin, P. Combemale, M. Dupin, B. Chouvet, J. Kanitakis, M.L. Bouyssou-Gauthier, et al.
The atrophic variant of dermatofibrosarcoma protuberans in childhood: a report of six cases.
Br J Dermatol, 139 (1998), pp. 719-725
[18.]
C.D. Fletcher.
Giant cell fibroblastoma of soft tissue: a clinicopathological and immunohistochemical study.
Histopathology, 13 (1988), pp. 499-508
[19.]
B.M. Shmookler, F.M. Enzinger, S.W. Weiss.
Giant cell fibroblastoma. A juvenile form of dermatofibrosarcoma protuberans.
Cancer, 64 (1989), pp. 2154-2161
[20.]
S.D. Billings, A.L. Folpe.
Cutaneous and subcutaneous fibrohistiocytic tumors of intermediate malignancy: an update.
Am J Dermatopathol, 26 (2004), pp. 141-155
[21.]
M.S. Pearce, L. Parker, S.J. Cotterill, P.M. Gordon, A.W. Craft.
Skin cancer in children and young adults: 28 years’ experience from the Northern Region Young Person's Malignant Disease Registry, UK.
Melanoma Res, 13 (2003), pp. 421-426
[22.]
L. Barnes, J.A. Coleman Jr., J.T. Johnson.
Dermatofibrosarcoma protuberans of the head and neck.
Arch Otolaryngol, 110 (1984), pp. 398-404
[23.]
M.P. Mbonde, H. Amir, J.N. Kitinya.
Dermatofibrosarcoma protuberans: a clinicopathological study in an African population.
East Afr Med J, 73 (1996), pp. 410-413
[24.]
M.E. Bashara, K.T. Jules, G.K. Potter.
Dermatofibrosarcoma protuberans: 4 years after local trauma.
J Foot Surg, 31 (1992), pp. 160-165
[25.]
A. Tanaka, M. Hatoko, H. Tada, M. Kuwahara, H. Iioka, K. Niitsuma.
Dermatofibrosarcoma protuberans arising from a burn scar of the axilla.
Ann Plast Surg, 52 (2004), pp. 423-425
[26.]
A. Argiris, C. Dardoufas, K. Aroni.
Radiotherapy induced soft tissue sarcoma: an unusual case of a dermatofibrosarcoma protuberans.
Clin Oncol (R Coll Radiol), 7 (1995), pp. 59-61
[27.]
J.J. Green, W.R. Heymann.
Dermatofibrosarcoma protuberans occurring in a smallpox vaccination scar.
J Am Acad Dermatol, 48 (2003), pp. S54-S55
[28.]
I. Bukhari, O. Al Akloby, Y. Bedaiwi.
Dermatofibrosarcoma protuberans at the site of a central venous line. Case report.
Am J Clin Dermatol, 6 (2005), pp. 61-64
[29.]
S.D. Kim, J.Y. Park, W.S. Choi, S.H. Kim, D.J. Lim, H.S. Chung.
Intracranial recurrence of the scalp dermatofibrosarcoma.
Clin Neurol Neurosurg, (2006),
[30.]
L. Loss, N.C. Zeitouni.
Management of scalp dermatofibrosarcoma protuberans.
Dermatol Surg, 31 (2005), pp. 1428-1433
[31.]
L.G. Rabinowitz, M.E. Luchetti, A.D. Segura, N.B. Esterly.
Acrally occurring dermatofibrosarcoma protuberans in children and adults.
J Dermatol Surg Oncol, 20 (1994), pp. 655-659
[32.]
L. Martin, F. Piette, P. Blanc, L. Mortier, M.F. Avril, M.M. Delaunay, et al.
Clinical variants of the preprotuberant stage of dermatofibrosarcoma protuberans.
Br J Dermatol, 153 (2005), pp. 932-936
[33.]
H. Kamino, M. Jacobson.
Dermatofibroma extending into the subcutaneous tissue. Differential diagnosis from dermatofibrosarcoma protuberans.
Am J Surg Pathol, 14 (1990), pp. 1156-1164
[34.]
B.W. Zelger, D. Ofner, B.G. Zelger.
Atrophic variants of dermatofibroma and dermatofibrosarcoma protuberans.
Histopathology, 26 (1995), pp. 519-527
[35.]
S. Aiba, N. Tabata, H. Ishii, H. Ootami, H. Tagami.
Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34.
Br J Dermatol, 127 (1992), pp. 79-84
[36.]
H. Kutzner.
Expression of the human progenitor cell antigen CD34 (HPCA-1) distinguishes dermatofibrosarcoma protuberans from fibrous histiocytoma in formalin-fixed, paraffin-embedded tissue.
J Am Acad Dermatol, 28 (1993), pp. 613-617
[37.]
S.E. Cowper, T. Kilpatrick, S. Proper, M.B. Morgan.
Solitary fibrous tumor of the skin.
Am J Dermatopathol, 21 (1999), pp. 213-219
[38.]
V.N. Hanft, C.R. Shea, N.S. McNutt, D. Pullitzer, M.G. Horenstein, V.G. Prieto.
Expression of CD34 in sclerotic (“plywood”) fibromas.
Am J Dermatopathol, 22 (2000), pp. 17-21
[39.]
J.F. Fetsch, W.B. Laskin, M. Miettinen.
Superficial acral fibromyxoma: a clinicopathologic and immunohistochemical analysis of 37 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes.
Hum Pathol, 32 (2001), pp. 704-714
[40.]
J.M. McNiff, A. Subtil, S.E. Cowper, R. Lazova, E.J. Glusac.
Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.
J Cutan Pathol, 32 (2005), pp. 413-418
[41.]
A.H. Diwan, M.G. Horenstein.
Dermatofibrosarcoma protuberans association with nuchal-type fibroma.
J Cutan Pathol, 31 (2004), pp. 62-66
[42.]
R. Sachdev, U. Sundram.
Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa.
J Cutan Pathol, 33 (2006), pp. 353-360
[43.]
B. Cribier, G. Noacco, B. Peltre, E. Grosshans.
Stromelysin 3 expression: a useful marker for the differential diagnosis dermatofibroma versus dermatofibrosarcoma protuberans.
J Am Acad Dermatol, 46 (2002), pp. 408-413
[44.]
R.B. West, J. Harvell, S.C. Linn, C.L. Liu, W. Prapong, T. Hernández-Boussard, et al.
Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans.
Am J Surg Pathol, 28 (2004), pp. 1063-1069
[45.]
T. Mentzel, A. Beham, D. Katenkamp, A.P. DeiTos, C.D. Fletcher.
Fibrosarcomatous (“high-grade”) dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance.
Am J Surg Pathol, 22 (1998), pp. 576-587
[46.]
C. Díaz-Cascajo, W. Weyers, L. Borrego, J.B. Inarrea, S. Borghi.
Dermatofibrosarcoma protuberans with fibrosarcomatous areas: a clinico-pathologic and immunohistochemic study in four cases.
Am J Dermatopathol, 19 (1997), pp. 562-567
[47.]
J.J. Abbott, A.M. Oliveira, A.G. Nascimento.
The prognostic significance of fibrosarcomatous transformation in dermatofibrosarcoma protuberans.
Am J Surg Pathol, 30 (2006), pp. 436-443
[48.]
B. Llombart, O. Sanmartín, J.A. López-Guerrero, C. Monteagudo, S. Calabuig, R. Botella, et al.
[Analysis of the COL1A1-PDGFB fusion gene in a case of dermatofibrosarcoma protuberans with a fibrosarcoma component].
Actas Dermosifiliogr, 97 (2006), pp. 337-341
[49.]
J.J. Abbott, M. Erickson-Johnson, X. Wang, G. Nascimento, A.R. Oliveira.
Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.
Mod Pathol, 19 (2006), pp. 1512-1518
[50.]
D.J. Sheehan, V. Madkan, W.A. Strickling, C.M. Peterson.
Atrophic dermatofibrosarcoma protuberans: a case report and reappraisal of the literature.
Cutis, 74 (2004), pp. 237-242
[51.]
C.R. Young 3rd, M.J. Albertini.
Atrophic dermatofibrosarcoma protuberans: case report, review, and proposed molecular mechanisms.
J Am Acad Dermatol, 49 (2003), pp. 761-764
[52.]
V. Sabater-Marco, A. Pérez-Valles, F. Berzal-Cantalejo, M. Rodríguez-Serna, F. Martínez-Díaz, M. Martorell-Cebollada.
Sclerosing dermatofibrosarcoma protuberans (DFSP): an unusual variant with focus on the histopathologic differential diagnosis.
Int J Dermatol, 45 (2006), pp. 59-62
[53.]
A. Sanz-Trelles, A. Ayala-Carbonero, I. Rodrigo-Fernández, B. Weil-Lara.
Leiomyomatous nodules and bundles of vascular origin in the fibrosarcomatous variant of dermatofibrosarcoma protuberans.
J Cutan Pathol, 25 (1998), pp. 44-49
[54.]
S.S. Banerjee, M. Harris, B.P. Eyden, B.N. Hamid.
Granular cell variant of dermatofibrosarcoma protuberans.
Histopathology, 17 (1990), pp. 375-378
[55.]
J.A. Bridge, J.R. Neff, A.A. Sandberg.
Cytogenetic analysis of dermatofibrosarcoma protuberans.
Cancer Genet Cytogenet, 49 (1990), pp. 199-202
[56.]
F. Pedeutour, J.M. Coindre, G. Sozzi, G. Nicolo, A. Leroux, S. Toma, et al.
Supernumerary ring chromosomes containing chromosome 17 sequences. A specific feature of dermatofibrosarcoma protuberans?.
Cancer Genet Cytogenet, 76 (1994), pp. 1-9
[57.]
F. Pedeutour, M.P. Simon, F. Minoletti, G. Sozzi, M.A. Pierotti, F. Hecht, et al.
Ring 22 chromosomes in dermatofibrosarcoma protuberans are low-level amplifiers of chromosome 17 and 22 sequences.
Cancer Res, 55 (1995), pp. 2400-2403
[58.]
F. Minoletti, M. Miozzo, F. Pedeutour, L. Sard, S. Pilotti, A. Azzarelli, et al.
Involvement of chromosomes 17 and 22 in dermatofibrosarcoma protuberans.
Genes Chromosomes Cancer, 13 (1995), pp. 62-65
[59.]
R. Naeem, M.L. Lux, S.F. Huang, S.P. Naber, J.M. Corson, J.A. Fletcher.
Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22.
Am J Pathol, 147 (1995), pp. 1553-1558
[60.]
M.J. Terrier-Lacombe, L. Guillou, G. Maire, P. Terrier, D.R. Vince, N. de Saint Aubain Somerhausen, et al.
Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data – a study from the French Federation of Cancer Centers Sarcoma Group.
Am J Surg Pathol, 27 (2003), pp. 27-39
[61.]
A. Shimizu, K.P. O’Brien, T. Sjoblom, K. Pietras, E. Buchdunger, V.P. Collins, et al.
The dermatofibrosarcoma protuberansassociated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGFBB.
Cancer Res, 59 (1999), pp. 3719-3723
[62.]
G.A. McArthur, G.D. Demetri, A. van Oosterom, M.C. Heinrich, M. Debiec-Rychter, C.L. Corless, et al.
Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225.
J Clin Oncol, 23 (2005), pp. 866-873
[63.]
M. Fiore, R. Miceli, C. Mussi, S. Lo Vullo, L. Mariani, L. Lozza, et al.
Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate.
J Clin Oncol, 23 (2005), pp. 7669-7675
[64.]
H.M. Gloster Jr., K.R. Harris, R.K. Roenigk.
A comparison between Mohs micrographic surgery and wide surgical excision for the treatment of dermatofibrosarcoma protuberans.
J Am Acad Dermatol, 35 (1996), pp. 82-87
[65.]
C.K. Chang, I.A. Jacobs, G.I. Salti.
Outcomes of surgery for dermatofibrosarcoma protuberans.
Eur J Surg Oncol, 30 (2004), pp. 341-345
[66.]
S.N. Snow, E.M. Gordon, P.O. Larson, M.M. Bagheri, M.L. Bentz, D.B. Sable, et al.
Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature.
Cancer, 101 (2004), pp. 28-38
[67.]
J. Wacker, B. Khan-Durani, W. Hartschuh.
Modified Mohs micrographic surgery in the therapy of dermatofibrosarcoma protuberans: analysis of 22 patients.
Ann Surg Oncol, 11 (2004), pp. 438-444
This article was funded in part by a grant from the regional government of Valencia (Generalitat Valenciana), Spain (grant GV06/274).
Copyright © 2007. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
