Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma Protuberans

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Dermatofibrosarcoma protuberans (DFSP) is a relatively uncommon soft tissue neoplasm of intermediate- to low-grade malignancy. Metastasis rarely occurs. DFSP is a locally aggressive tumor with a high recurrence rate.

Although DFSP may have been reported in the literature as early as 1890, Darier and Ferrand first described it in 1924 as a distinct cutaneous disease entity called progressive and recurring dermatofibroma. Hoffman officially coined the term dermatofibrosarcoma protuberans in 1925. [1] Note the images below.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous malignancy that arises from the dermis and invades deeper tissue (eg, fat, fascia, muscle, bone).

The cellular origin of DFSP is not clear. Evidence supports the cellular origin being fibroblastic, histiocytic, or neuroectodermal. DFSP manifests partial features of each. Therefore, many authorities suggest pluripotential progenitor cells, such as undifferentiated mesenchymal cells, may be the origin of DFSP, because they have the capacity to differentiate into all 3 cell types. [2]

Cultured DFSP tumor cells have increased growth in response to platelet-derived growth factor (PDGF)–beta. Cytogenetic studies reveal specific abnormalities in DFSP tumor cells, such as reciprocal translocations of chromosomes 17 and 22, t(17;22), and supernumerary ring chromosomes composed of interspersed sequences from bands 17(17q22) and 22(22q12). These rearrangements fuse the collagen type I alpha 1 (COL1A1) and the PDGF-beta chain (PDGFB, c-sis proto-oncogene) genes. The collagen promoter drives COL1A1 and PDGFB fusion protein production. The fusion protein is then processed into functional PDGF-B and subsequently interacts with the PDGF receptor on the cell surface of DFSP tumor cells. The activation of the PDGF receptor tyrosine kinase triggers the proliferation of DFSP tumor cells. [2, 3, 4, 5, 6, 7, 8]

The cause of dermatofibrosarcoma protuberans (DFSP) is unknown. Laboratory studies have shown that chromosomal aberrations may contribute to the pathogenesis of DFSP; however, no evidence of hereditary or familial predisposition exists. In 10-20% of patients with this tumor, trauma at the site seems to be incriminated. Surgical and burn scars and sites of vaccinations have been reported as sites of DFSP. [9]

United States

Dermatofibrosarcoma protuberans (DFSP) accounts for less than 0.1% of all malignant neoplasms and approximately 1% of all soft tissue sarcomas. DFSP is the most common type of cutaneous sarcoma. The incidence of DFSP has been estimated to be 0.8-5 case per million population per year in 2 separate studies. [2] In a another study based on data from 9 cancer registries from 1973-2002, the annual incidence of DFSP in the United States is 4.2 cases per million population per year. [8]

International

The annual incidence of DFSP is reported as 3 cases per million population from a population-based cancer registry from 1982-2002 in France. [10] A study of the population-based National Cancer Registry shows the incidence of DFSP is approximately 4 cases per million per year in Sweden from 1990-2005. [11]

Dermatofibrosarcoma protuberans (DFSP) has been reported in persons of all races, and no racial predilection seems to exist in previous reports. However, a study conducted by Criscione and Weinstock found the incidence among African Americans (6.5 cases per million population) was almost double the incidence among American whites (3.9 cases per million population).

An uncommon pigmented variant of DFSP, accounting for 1% of all DFSP cases, is called the Bednar tumor. Annual incidence of Bednar tumor among blacks is 7.5 times higher than that of white patients. [8] Note the images below.

Several studies of dermatofibrosarcoma protuberans (DFSP) reveal an almost equal sexual distribution or a slight male predominance. In a large study of 902 patients with DFSP conducted by Rutgers et al, 514 (57%) patients were male and 388 (43%) patients were female. [12] A study based on 405 DFSP cases from the Swedish National Cancer Registry between 1990 and 2005 shows a very small difference in annual incidence of male (4.4 cases per million) versus female (4.0 cases per million). [11] However, a larger cancer registry study of 2885 cases reveals females might have a slightly higher incidence of DFSP, 4.4 cases versus 4.2 cases per million population per year. [8]

Dermatofibrosarcoma protuberans (DFSP) usually occurs in adults aged 20-50 years. Rarely, DFSP has been reported in newborns and elderly individuals (80 y). [13]

Dermatofibrosarcoma protuberans (DFSP) is characterized by its aggressive local invasion. The tumor invades local tissue by extending tentaclelike projections underneath healthy skin, rendering complete removal of the tumor very difficult. Incomplete removal of these neoplastic cells results in a high local recurrence rate.

Despite the local invasiveness, DFSP rarely metastasizes. For the classic form of DFSP, the risk is assumed to be only 0.5%. According to the literature, the overall risk for the development of metastatic disease is 5%, including 1% with regional lymph node metastasis and 4% with distant metastasis. Regional lymph node involvement represents a sign of poor prognosis; most patients die within 2 years. [8] The lungs are the most common site of distant metastasis that occurs via hematogenous spread. Usually, metastatic disease is preceded by multiple local recurrences. [14]

A small subset of DFSP patients presents with fibrosarcomatous progression. This fibrosarcomatous progression DFSP variant is more aggressive in nature, and the clinical outcome usually is poor. [15]

The extent of surgical excision determines the prognosis for the patient. To reduce the local recurrence rate, a wide surgical excision with adequate margins or Mohs technique are used. The latter imparts a better outcome.

Histologic features of DFSP may also serve as prognostic indicators. A high number of mitotic figures, increased cellularity, DNA aneuploidy, TP53 gene overexpression, and the presence of fibrosarcomatous changes within the tumor are poor prognostic indicators. Of note, fibrosarcomatous variants of DFSP lacking a genetic marker of translocation between chromosomes 17 and 22 may not respond to imatinib. The loss of the t(17,22) cytogenetic marker in the fibrosarcomatous progression DFSP variant may represent progression of the malignancy. [1, 16, 17]

Age older than 50 years is also a risk factor associated with a poor clinical outcome. [18]

Patients are advised to seek evaluation by a dermatologist if they have noticed a slow-growing skin lump or scarlike lesion on any part of their body.

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Raman K Madan, MD Resident Physician, Department of Dermatology, State University of New York Downstate Medical Center

Disclosure: Nothing to disclose.

Georgina Marie Ferzli, MD, MS Resident Physician, Department of Dermatology, State University of New York Downstate Medical Center

Disclosure: Nothing to disclose.

Stephanie M Gallitano, MD Resident Physician, Department of Dermatology, State University of New York Downstate Medical Center

Stephanie M Gallitano, MD is a member of the following medical societies: American Academy of Dermatology, Women’s Dermatologic Society

Disclosure: Nothing to disclose.

Chih-Shan Jason Chen, MD, PhD Attending Physician, Dermatology Service, Memorial Sloan-Kettering Cancer Center; Director, Dermatologic Surgery and Mohs Micrographic Surgery Unit, MSK Skin Cancer Center; Chief, Dermatologic Surgery, Northport Veterans Affairs Medical Center; Associate Professor of Clinical Dermatology, Stony Brook University School of Medicine

Chih-Shan Jason Chen, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery, Association of Professors of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Daniel Mark Siegel, MD, MS Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate Medical Center

Daniel Mark Siegel, MD, MS is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Association for Physician Leadership, American Society for Dermatologic Surgery, American Society for MOHS Surgery, International Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: QualDerm Partners; Novascan<br/>Have a 5% or greater equity interest in: QualDerm Partners – North Carolina.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Abdul-Ghani Kibbi, MD Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Dermatofibrosarcoma Protuberans

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