Liddy Shriver Sarcoma Initiative on Facebook    Follow Us on Google Plus    Follow Us on Twitter    Sarcoma Videos on YouTube

The Faces of DFSP

Photos of people with DFSP from around the world. Learn more.

What is Dermatofibrosarcoma Protuberans?

Dermatofibrosarcoma Protuberans (DFSP) is a rare type of cancer, a soft tissue sarcoma that develops in the deep layers of skin. It is sometimes described as having tentacles that can grow into surrounding fat, muscle and even bone. DFSP is most commonly found on the torso, but can also be seen on the arms, legs, head and neck. It has a tendency to recur in the same location after it is removed. However, it only spreads to other parts of the body in about 5% of cases.

DFSP most often starts as a small, firm patch of skin, approximately one to five centimeters in diameter. The skin is occasionally flat or depressed. It can be purplish, reddish or flesh-colored. The tumor typically grows very slowly (over months to years) and can become a raised nodule.

DFSP tends to affect people between the age of 20 and 50, but it has been diagnosed in people of all ages. There are about 1,000 cases diagnosed in the United States each year, with an incidence of about 1-5 people per million. The tumors affect black patients about twice as much as white patients.

Rare Variants of DFSP

There are several variations of DFSP that can be identified under a microscope:

  1. Bednar tumors (pigmented DFSP) contain dark-colored cells called melanin-containing dendritic cells. Melanin is the substance that gives skin its color. As a result, this type of tumor may contain various colors, including red and brown. Bednar tumors account for approximately 1%-5% of all DFSP cases.
  2. Myxoid DFSP tumors contain an abnormal type of connective tissue that is called myxiod stroma. This type of tumor is uncommon, presents a diagnostic challenge and is important to recognize in order to prevent both under- and over-treatment.
  3. Giant cell fibroblastoma, referred to as juvenile DFSP because it typically affects children and adolescents, is characterized by giant cells in the tumor. It appears to be histologically similar to DFSP and in rare instances can be found within the same tumor in conjunction with DFSP, resulting in a hybrid lesion.
  4. Rarely, the tumors involved in the different types of DFSP can have regions that look familiar to fibrosarcoma, a more aggressive type of soft tissue sarcoma. In these cases, the condition is called Fibrosarcomatous (FS) DFSP. These tumors are more likely to metastasize than tumors in the other types of DFSP.

What are the risks factors or causes of DFSP?

It is not clear what causes this type of skin cancer. A scar that develops after a burn or surgery may increase the risk for developing DFSP. Women, adults between the ages of 30 and 50, and African-Americans are at a higher risk of developing the disease, particularly the Bendar or pigmented variant. Pregnant women who have DFSP may have fast-growing tumors.

DFSP is associated with a re-arrangement of genetic material between chromosomes 17 and 22. It is the result of a new mutation that occurs in the body’s cells after conception and is found only in the tumor cells. DFSP is not believed to be a hereditary condition.

What are signs and symptoms of DFSP?

The first sign is generally a flat or slightly raised patch of skin that feels rubbery or hard to the touch. It often looks like a scar or wrinkled patch of skin that may be violet, reddish brown or skin-colored. Rarely, DFSP presents as a soft, depressed area of skin, which makes the diagnosis even more difficult.

As DFSP grows, a violet, reddish brown or skin-colored tumor may appear, sometimes more than one. By the time a tumor appears, the cancer is usually growing more rapidly and the tumor(s) may open up, bleed or become painful. However, redness and pain only occur in 15% of cases.

Skin changes that warrant a visit to a dermatologist:

  • Growth on the skin that does not go away in two weeks
  • Change in a scar, especially one caused by surgery or a burn
  • Anything that is quickly growing or changing on the skin

How is DFSP diagnosed?

The absence of symptoms often leads to a delay in diagnosis. DFSP is often mistaken for other skin conditions, particularly in its early stages. It is frequently diagnosed when it enters a more rapid growth phase, giving rise to larger lesions.

If a dermatologist suspects skin cancer, a biopsy is performed. This procedure can be safely conducted during an office visit. To perform a biopsy, the dermatologist will remove the suspicious lesion, or part of it, so that it can be examined under a microscope. This is the only way to know if a person has skin cancer.

An MRI may be helpful to evaluate the extent (severity) of the tumor and may be important for pre-surgery considerations of larger tumors. The American Musculoskeletal Tumor Society Staging System is used in order to indicate tumor grade or classification.

How is DFSP treated?

Most cases of DFSP can be adequately treated by a dermatologist, as he or she is a specialist who routinely diagnoses and treats lesions of the skin. However, in cases of very large or advanced DFSPs, or when major reconstructive surgery is indicated, a multi-disciplinary approach may be necessary. This team may involve a dermatologist, pathologist, radiologist, oncologist, radiation oncologist, orthopedic surgeon (specializing in tumor surgery) and plastic surgeon (for reconstruction, if the tumor has invaded deep tissues and bone).

In determining what type of treatment is appropriate, a dermatologist will consider how deeply in to the skin the tumor has grown, where it is located on the person’s body and the person’s overall health. Treatment options include:

  1. Mohs micrographic surgery involves removing one layer of skin at a time. Each layer that is removed is then placed under a microscope in order to look for cancer cells. The process continues until cancer cells are no longer found. The procedure is most often performed in a dermatologist’s office with local anesthesia. Because the treatment continues until cancer cells are no longer found, Mohs surgery reduces the risk that the DFSP will return.
  2. Excision is a surgical procedure that may be utilized if a tumor is large in size. It involves surgically removing the DFSP and a portion of normal-looking skin. The procedure may be performed in a dermatologist’s office or in some cases, an operating room.

In cases of advanced DFSP, the cancer has grown deeply and may have reached muscle or bone, even spreading to other parts of the body in rare instances. More than one treatment may be used to increase the likelihood that all of the cancer is killed or removed. Treatment options for advanced DFSP include:

  1. Systemic Therapy: While chemotherapy does not appear to be beneficial, the targeted therapy Imatinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of DFSP. It targets and turns off proteins that allow cancer cells to grow. It is not meant to treat every person with DFSP, only those with DFSP that cannot be removed with surgery or DFSP that keeps returning or has spread to other parts of the body. In some persons with advanced DFSP, imatinib mesylate may be taken before surgery in order to reduce the size of the tumor and make surgery more effective. Using both the medication and surgery to treat advanced DFSP has been shown to greatly reduce the risk of DFSP returning.
  2. Radiation therapy: As DFSP can return after treatment, this option may be prescribed, albeit rarely. It is usually only given after surgery, when the risk of DFSP returning is high. It may also be a treatment option for someone with DFSP who cannot have surgery.

What is the prognosis for persons with DFSP?

The general prognosis for DFSP is excellent. In the past, recurrence rates were high, but with the introduction of Mohs surgery, those rates have decreased. Even with recurrent DFSP, Mohs surgery has a 98% cure rate.

A poor prognosis is associated with metastasis. However, recent results for patients with metastasis using Imatinib are encouraging.

How are patients followed after treatment?

Continuing to see a dermatologist is essential. When DFSP returns, it is often within three years of treatment. Thus, during the first three years after treatment, people with a history of DFSP should return for follow-up examinations every three to six months. After this three-year period, a thorough annual examination is recommended for the duration of the patient’s life.

Last revision and medical review: 12/2012

By Leanne E. Lucia

Print it

Dermatofibrosarcoma Protuberans

Introduction

Dermatofibrosarcoma protuberans (DFSP) is a low to intermediate grade soft-tissue sarcoma originating from the dermal layer of the skin. Although historically it has been attributed to fibroblastic origin, DFSP is now thought to originate from mesenchymal stem cells according to the currently dominant cancer stem cell hypothesis.In 1924, Darier and Ferrand first described the entity of DFSP as a "progressive and recurring dermatofibroma," underscoring its predilection for local recurrence.2 DFSP is a locally aggressive tumor and despite sharing some histologic features with fibrohistiocytic tumors, it tends to grow in a more infiltrative manner. Three-dimensional reconstructions of DFSP have shown that the tumor can assume irregular shapes and extend in a villous or finger-like manner.3 

These irregular, tentacle-like extensions are believed to be responsible for the common clinical dilemma of local recurrence following inadequate resection.4 Metastases are rare and usually occur late in the disease course.

Epidemiology

DFSP comprises roughly .01% of all malignant tumors and approximately 2 to 6 percent of all soft-tissue sarcomas.5-6 The estimated incidence is 0.8 to 5 cases per 1 million persons per year,7-11 which is roughly 1,000 new cases per year in America. The incidence among blacks (6.5 per million) is almost double that among whites (3.9 per million).12  It most commonly affects patients between 20 and 50 years of age, although it has been described in both children and in the elderly.13 Congenital DFSP is a recognized entity but is extremely uncommon.13-16

Figure 1

Figure 1: Photograph of DFSP...

Clinical Features

DFSP usually has a long slow indolent course, with early tumors appearing as painless areas of cutaneous thickening (Figure 1). They may have pink, dark red or even bluish discoloration, particularly at the periphery. Over time, they develop into a larger nodular mass, and ultimately can develop into a large fungating lesion (Figure 2). When they grow into the epidermal layer of the skin, they may eventually ulcerate. Unlike tumors of the subcutaneous tissue, DFSP is adherent or intimate with its overlying skin. Typically it is not adherent to underlying structures, with most tumors being superficial and less than 5 cm in size at time of diagnosis.17

Figure 2

Figure 2: An advanced, large fungating DFSP overlying the...

The duration of tumor growth ranges from months to years and may, in some cases, span decades. DFSP often is mistaken for lipomas, deep-seated epidermal cysts, scars, hypertrophic scars, keloids, dermatofibromas, nodular fasciitis, and insect bites18 and a delayed diagnosis is not uncommon. The trunk is the most common location (47%), followed by lower extremity (20%), upper extremity (18%), and finally head and neck (14%).17

DFSP is a malignant tumor, but only metastasizes 1-4% of the time.17 Metastasis is a late clinical outcome and typically occurs only after several local recurrences.19

Diagnosis of DFSP

Although routine imaging is not necessary, magnetic resonance imaging (MRI) may be helpful to evaluate the gross local extent of the tumor and may be important in preoperative planning for larger tumors. As with many other soft tissue tumors, T1-weighted images demonstrate low signal characteristics while T2-weighted images exhibit higher signal. While MRI can adequately delineate the bulk of the tumor, it does not define microscopic tumor extension. Furthermore, it does not clearly define recurrent lesions or lateral infiltration which is typical of this entity.20  In patients with prolonged or recurrent DFSP or when sarcomatous changes are evident (DFSP-FS (see below)) a CT of the chest should be obtained to evaluate for pulmonary metastases.4 A CT scan of the local area may be useful if bony involvement is suspected.4

Diagnosis is made using either a core needle or an open incisional biopsy. While the role of fine needle aspiration is established in cases of recurrent disease, initial biopsies should be larger samples that demonstrate the histologic architecture of the tumor.21

Biopsy

A core needle biopsy (or core biopsy) involves removal of a very small amount of tumor and is performed by inserting a hollow needle through the skin and into the organ or abnormality to be investigated. The needle is then advanced within the cell layers to remove a sample or core. This procedure takes a few minutes to perform and may be undertaken in an outpatient setting.

An incisional biopsy removes only a portion of the tumor for the pathologist to examine. An incisional biopsy is generally reserved for tumors that are larger and offers the pathologist a larger specimen with which to work.  This type of biopsy has a slightly higher diagnostic success rate and is usually carried out in the operating room.

An excisional biopsy involves removal of the entire tumor and is typically reserved for very small lesions in which an incisional biopsy or a core needle biopsy is not practical.  It is usually performed in cases where removing the entire lesion along with a narrow margin of normal tissue is easily accomplished and tolerated by the patient.  This is also often performed in the operating room.

Staging

Although the American Joint Committee on cancer has not set forth a system specific for staging of DFSP, it is often staged according to the American Musculoskeletal Tumor Society Staging System which is based upon tumor grade and compartmentalization.22 A more recently published system in accordance with the Short German guidelines for DFSP distinguishes local tumor (Grade I) from nodal dissemination (Grade II) and from metastatic disease (Grade III).23

Histopathology

Figure 3

Figure 3: DFSP composed of slender fibroblasts arranged in a storiform...

DFSP has a characteristic histologic appearance of monomorphous bland spindle cells arranged in a storiform or "whorled" pattern (Figure 3). Early lesions may demonstrate a "Grenz zone," which is a tumor-free region separating the tumor from the epidermis. Unusual variants of DFSP include the Bednar tumor that is denoted by melanin-containing cells,24 myxoid DFSP that contains areas of interstitial mucin, and the atrophic type.

Approximately 15% of cases contain a component of high-grade sarcoma. This is frequently, but not exclusively, a fibrosarcoma and therefore is usually referred to as DFSP-FS. The high-grade sarcoma portion can be variable in size, at times encompassing the majority of the underlying DFSP lesion. Even in cases that develop a high grade sarcomatous component, metastatic disease is rare and local recurrence remains the main concern.

Figure 4

Figure 4: Extensive positivity is typically seen with CD34 staining...

Immunohistochemical analysis can be utilized to aid in the diagnosis. Staining for CD34 is commonly employed, and sensitivity has been reported as being between 84 and 100 percent (Figure 4).25-27 Positivity for CD34 is lost within the areas of sarcomatous change in cases of DFSP-FS. In addition, staining for hyaluronate and vimentin is expected to be positive in DFSP, while staining for CD44, factor XIIIa and S100 is expected to be negative. Apolipoprotein D is expressed in DFSP and may be useful in differentiating the tumors from malignant fibrous histiocytoma (DFSP tx c PDGF receptor inhibitor).  Furthermore, the fusion gene COL1A1/PDGFB can be detected in the tissue by means of FISH (fluorescence in-situ hybridization).28

Genetics

There is evidence that DFSP may originate from cutaneous mesenchymal stem cells that code for a cell surface protein termed nestin.29 Nestin may also be useful for differentiating DFSP from dermatofibromas and may have application in intraoperative staining in the context of Moh’s surgery.

More than 90% of DFSPs exhibit a specific cytogenetic abnormality, either a supernumerary ring chromosome combining chromomoses 17 and 22 or an unbalanced chromosomal translocation between chromosomes 17 and 22.  It is now evident that the ring chromosomes are the more common abnormality and the translocation is typically only found in pediatric DFSP.1,4  Regardless, the result is identical, and is defined by the fusion of the platelet-derived growth factor-B gene (PDGFB; chromosome 22) with the strongly expressed collagen 1 alpha 1 gene (COL1A1; chromosome 17). This leads to upregulated expression of the fusion oncogene and fully functional PDGFB.30-32 This serves as a self-stimulatory or autocrine growth signal, which in turn leads to uncontrolled cell division and tumorigenesis.  Nonetheless, in 8% of cases of otherwise confirmed DFSP, the fusion transcript of COL1A1 and PDGFB is not identified, suggesting possible additional genes that may be involved in DFSP.4

Chromosomal Translocations

A chromosomal translocation is an abnormal rearrangement of DNA between chromosomes.  When the translocation occurs between two nonhomologous chromosomes, it is termed a reciprocal translocation. Reciprocal translocations are usually harmless in carriers; however, there is an increased risk for miscarriages or children with abnormalities. A Robertsonian translocation involves two acrocentric chromosomes that fuse near the centromere region with loss of the short arms. The resulting karyotype leaves only 45 chromosomes since two chromosomes have fused together. Like other translocations, carriers of Robertsonian translocations are phenotypically normal, but there is a risk of unbalanced gametes which lead to miscarriages or abnormal offspring.

Treatment of Dermatofibrosarcoma Protuberans

The mainstay of treatment of DFSP has been surgery.  Because of the high rates of recurrence, historical recommendations have sought 5 cm margins.33

Who treats DFSP?

Dermatologists routinely diagnose and treat lesions of the skin. Most cases of DFSP can be adequately treated by a dermatologist in an outpatient setting. In cases of very large or advanced DFSP, or where major reconstructive surgery will be needed, a multidisciplinary approach is recommended. This involves an oncologist, dermatologist, and a pathologist. In cases involving the deep tissues or bones, the participation of an orthopaedic surgeon specializing in tumor surgery may be necessary. In cases where extensive surgical reconstruction will be necessary, a plastic surgeon may be called upon.

Figures 5-7

Figures 5-7: Series of Surgical Photos...

Recent NCCN guidelines recommend margins of 2 to 4 cms using conventional surgical management (Figures 5-7). Local recurrences can often be salvaged with further resection but the risk of local morbidity and the risk of metastasis both increase.  Occasionally, isolated metastatic disease can be surgically addressed.4

With the advent of Mohs surgery, complete excision with microscopic margins has yielded excellent outcomes and offers the benefit of decreased surgical morbidity. In a comparative study of wide resection versus Mohs surgery, wide resection was associated with a recurrence rate of 13% whereas Mohs surgery had no recurrences at 5 years.34 Evidence is accumulating that Mohs surgery is the optimal surgical choice for most DFSP lesions with the exceptions of the aforementioned large/advanced DFSP that may require more extensive surgical and reconstructive procedures.35,36

Mohs Surgery

Mohs surgery, created by Dr. Fredrick E. Mohs, is microscopically controlled surgery that is highly effective for common types of skin cancer. The surgery involves four steps:

  1. Surgical removal of tissue.
  2. Mapping the piece of tissue, freezing and cutting the tissue and staining with H&E or other stains.
  3. Interpretation of microscope slides.
  4. Reconstruction of the surgical defect.

The procedure is usually performed in a physician's office under local anesthetic. A small scalpel is utilized to cut around the visible tumor. A very small surgical margin is utilized, usually with 1 to 1.5 mm of "free margin" or uninvolved skin. Because the Mohs procedure is microscopically controlled, it provides precise removal of tumor, while healthy tissue is spared.

Conventional chemotherapy appears to offer little utility, however, treatment with the molecular targeted therapy Imatinib, has yielded some limited but encouraging results to date.4 Imatinib mesylate was designed as an abl-kinase inhibitor to treat Philadelphia chromosome positive leukemia (chronic myelogenous leukemia). Imatinib inhibits two additional kinases: c-KIT and PDGFR accounting for its efficacy in DFSP.28  The application of Imatinib to DFSP has been limited but encouraging.  In one series, 10 patients with either locally advanced or metastatic disease showed variable response to Imatinib treatment. Of note was the association shown in one patient between the lack of the t(17,22) translocation and the lack of response to Imatinib treatment.27 It is now the recommendation to perform  molecular analysis prior to initiating Imatinib treatment to ensure that a t(17:22) mutation exists.37  Additional reports of successful use in cases of metastatic or surgically unresectable DFSP have been published.  A female patient with recurrent DFSP of the upper back and metastasis to the axilla and lung responded well following one month of treatment. At 3 months, the tumor regressed markedly and computed tomography imaging showed near complete resolution of the lung metastasis.38 A male patient with DFSP of the thigh and metastatic disease of the spine was treated with Imatinib for 4 months and shown to have a 75% reduction in tumor size, permitting surgical resection. The resected tumor showed no signs of malignancy, demonstrating a full histopathologic response to treatment.39  Imatinib is approved for the treatment of adult patients with unresectable, recurrent, or metastatic DFSP who are not eligible for surgery. Response to Imatinib appears to be short-lived with many patients developing resistance through as of yet unknown mechanisms.  Nonetheless, the treatment has led to the resectability of tumors that were thought to be unresectable prior to treatment due to the proximity of adjacent vital structures.28

DFSP's Response to Imatinib

The effectiveness of Imatinib in the treatment of DFSP is likely related to the tumor’s dependence on this pathway with the common translocation driving the constitutive expression of the PDGF ligand. This is a unique example of a tumor that responds to a specific targeted therapy which is not based on genetic amplification or mutation. The limitation on developing imatinib clinically for the treatment of DFSP is that it is a benign to intermediate grade tumor in which complete surgical resection obviates the need for systemic therapy. Imatinib likely will be only applicable to the subset of patients with unresectable, recurrent or metastatic disease. However, phase II trials of treating DFSP with Imatinib are currently in progress and while some of them have recently been completed, only preliminary results are available to date.40-42 Additional PDGF receptor inhibitors, including sunitinib, pazopanib and sorafenib, are currently undergoing evaluation as well.4,43

Numerous studies have investigated the use of radiotherapy in the treatment of DFSP and DFSP is considered a radio-sensitive tumor. Currently, there is limited objective data to support its routine use; however, successful application has been reported in a few small series. In one study, 10 patients with DFSP (one of which was DFSP-FS) were treated with surgery and post-operative radiotherapy. At the time of latest follow-up (21-185 months) nine of the patients remained free from recurrence. The patient with DFSP-FS experienced a local recurrence and eventually died with disease.44 Radiation therapy (RT) can be used to decrease the risk of local recurrence when surgery and RT are combined. Haas et. al. studied 21 patients treated surgically, noting local control of 67% and in 17 patients treated with combined therapy (surgery and radiation therapy) the local control was 82%.45  In other reviews, it was concluded that adjuvant radiotherapy may be considered in patients where repeated surgery may cause mutilation or functional impairment.45-46

Prognosis

The general prognosis for DFSP is excellent. The overall rate of distant metastasis is only 5% and regional metastasis is 1%.47 Historically, recurrence rates have been high, ranging from 11%- 53%, but with the advent of Mohs surgery, the rates have dropped. Even with recurrent DFSP, Mohs surgery has a 98% cure rate.48

Metastasis is associated with a poor prognosis, with few patients surviving beyond two years. With initial encouraging results using Imatinib, improved prognosis even in cases of metastatic disease may be realized.

Last revised: 12/2012
Last medical review: 12/2012

By Kevin O'Halloran, MD1
Jonathan Courtney, MD1
Richard G. Gorlick, MD2
David S. Geller, MD1

1 Orthopaedic Oncology, Montefiore Medical Center
2 Vice Chairman, Department of Pediatrics, Children’s Hospital At Montefiore

References and Bibliography

1. Johnson-Jahangir H,  Ratner D,  Advances in Management of Dermatofibrosarcoma Protuberans.  Dermatol Clin 2011 29 191–200.

2.  Darier J, Ferrand M: Dermatofibromes progressifs et recidivants ou fibrosarcomes de la peau. Ann Dermatol Syphiliga 1924; 5:545-562.

3. Ratner D, Thomas CO, Johnson TM, Sondak VK, Hamilton TA, Nelson BR, Swanson NA, Garcia C, Clark RE, Grande DJ. Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread. J Am Acad Dermatol. 1997 Oct;37(4):600-13.

4.  Lemm D,  Mügge L-O,  Mentzel T,  Höffken K, Current treatment options in dermatofibrosarcoma protuberans.  J Cancer Res Clin Oncol 2009 135:653–665.

5. Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol. 2004 Apr;30(3):341-5.

6. Kransdorf MJ. Malignant soft-tissue tumors in a large referral population: distribution of diagnoses by age, sex, and location. AJR Am J Roentgenol. 1995 Jan;164(1):129-34.

7. Bendix-Hansen K, Myhre-Jensen D, Haae S: Dermatofibrosarcoma protuberans: a clinicopathological study of nineteen cases and a review of world literature. Scand J Plast Reconstruct Surg Hand Surg 1983; 17:247-252.

8. Burkhardt BR, Soule EH, Winkelmann RK, et al: Dermatofibrosarcoma protuberans: study of fifty-six cases. Am J Surg 1966; 111:638-644.

9. Pack GT, Tabah EJ: Dermatofibrosarcoma protuberans: a report of 39 cases. Arch Surg 1951; 62:391-411.

10. Chaung TY, Su WPD, Muller SA: Incidence of T cell lymphoma and other rare skin cancers in a defined population. J Am Acad Dermatol 1990; 23:254-256.

11. Gloster HM: Dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996; 35:355-374.

12. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007 Jun;56(6):968-73. Epub 2006 Dec 1.

13. Taylor HB, Helwig EB: Dermatofibrosarcoma protuberans: a study of 115 cases. Cancer 1962; 15:717-725.
14. McKee PH, Fletcher CD: Dermatofibrosarcoma protuberans in infancy and childhood. J Cutan Pathol 1991; 18:241- 246.

15. Schuarez LW: Congenital dermatofibrosarcoma protuberans of the hand. Hand 1977; 9:182-186.

16. Annessi G, Cimisan A, Girolomoni G, et al: Congenital dermatofibrosarcoma protuberans. Pediatr Dermatol 1993; 10:40-42.

17. Bowne WB, Antonescu CR, Leung DH, Katz SC, Hawkins WG, Woodruff JM, Brennan MF, Lewis JJ.

ermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution. Cancer. 2000 Jun 15;88(12):2711-20.

18. Abeloff MD. Abeloff’s Clinical Oncology. 4th ed. Philadelphia, PA: Elsevier; 2008: Ch 74.

19. Canale ST. Campbell’s Operative Orthopaedics. 10th ed. Philadelphia, PA: Mosby; 2003:86.

20.  Serra-Guillen C, Sanmartin O, Llombart B, Nagore E, Deltoro C, Martin I, Borella-Estrada R, Requena C, Martorell-Calatayud A, Cervera J, Guillen C. Correlation Between Preoperative Magnetic Resonance Imaging and Surgical Margins with Modified Mohs for Dermatofibrosarcoma Protuberans Dermatol Surg 2011;37:1638–1645.

21. Klijanienko J, Caillaud JM, Lagacé R. Fine-needle aspiration of primary and recurrent dermatofibrosarcoma protuberans. Diagn Cytopathol. 2004 Apr;30(4):261-5.

22. [No authors listed]. Soft tissue sarcoma. In: Greene PL, Page DL, Fleming ID, eds. AJCC cancer staging manual (6th edition). New York: Springer-Verlag. 2002; 193-200.

23. Ugurel S, Kortmann RD, Mohr P, Mentzel T, Garbe C, Breuninger H. Short German guidelines: Dermatofibrosarcoma protuberans J Dtsch Dermatol Ges. 2008 May;6 Suppl 1:S17-8.

24. Dupree WB, Langloss JW, Weiss SW: Pigmented dermatofibrosarcoma protuberans (Bednar tumor): a pathologic, ultrastructural and immunohistochemical study. Am J Surg Pathol 1985; 9:630-639.

25. Haycox CL, Odland PB, Olbricht SM, Piepkorn M. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol. 1997 Sep;37(3 Pt 1):438-44.

26. Abenoza P, Lillemoe T. CD34 and factor XIIIa in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. Am J Dermatopathol. 1993 Oct;15(5):429-34.

27. McArthur GA, Demetri GD, van Oosterom A, Heinrich MC, Debiec-Rychter M, Corless CL, Nikolova Z, Dimitrijevic S, Fletcher JA. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with Imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol. 2005 Feb 1;23(4):866-73.

28.  Malhotra B, Schuetze SM, Dermatofibrosarcoma protruberans treatment with platelet-derived growth factor receptor inhibitor: a review of clinical trial results Curr Opin Oncol. 2012 Jul;24(4):419-24.

29.  Sellheyer K,  Nelson P, Krahla D. Dermatofibrosarcoma protuberans: a tumour of
nestin-positive cutaneous mesenchymal stem cells? British Journal of Dermatology 2009 161, pp1317–1322.

30. Allan AE, Tsou HC, Harrington A, et al: Clonal origin of dermatofibrosarcoma protuberans. J Invest Dermatol 1993; 100:99-102.

31. Pedeutour F, Simon MP, Minoletti F, et al: Ring 22 chromosomes in dermatofibrosarcoma protuberans are low level amplifiers of chromosome 17 and 22l sequences. Cancer Res 1995; 55:2400-2403.

32. Bridge JA, Neff JR, Sanberg AA: Cytogenetic analysis of dermatofibrosarcoma protuberans. Cancer Genet Cytogenet 1990; 49:199-202.

33. Arnaud EJ, Perrault M, Revol M, Servant JM, Banzet P. Surgical treatment of dermatofibrosarcoma protuberans. Plast Reconstr Surg. 1997 Sep;100(4):884-95.

34. Paradisi A, Abeni D, Rusciani A, Cigna E, Wolter M, Scuderi N, Rusciani L, Kaufmann R, Podda M. Dermatofibrosarcoma protuberans: wide local excision vs. Mohs micrographic surgery. Cancer Treat Rev. 2008 Dec;34(8):728-36. Epub 2008 Aug 5.

35.  Love EW, Keiler SA, Tamburro JE, Honda K, Gosain AK, Bordeaux JS, Surgical management of congenital dermatofibrosarcoma protuberans J Am Acad Dermatol Dec 2009 Vol 61 Number 6.

36. Meguerditchian AN, Wang J, Lema B, Kraybill WG, Zeitouni NC, Kane JM III, Wide Excision or Mohs Micrographic Surgery for the Treatment of Primary Dermatofibrosarcoma Protuberans American Journal of Clinical Oncology June 2010 Volume 33, Number 3.

37. Voth H, Landsberg J, Hinz T, Wenzel J, Bieber T, Reinhard G, Holler T, Wendtner CM, Schmid-Wendtner MH. Management of dermatofibrosarcoma protuberans with fibrosarcomatous transformation: an evidence-based review of the literature Journal of the European Academy of Dermatology and Venereology Dec 2011, 25 (12), 1385–1391.

38. Labropoulos S., Papdopoulos S., Hadjiyiassemi D., Giannopoulou D., Razis E., Razis D., Response of metastatic dermatofibrosarcoma protuberans to Imatinib mesylate. [abstract] Proc Am Soc Clin Oncol (2003) 22 : pp 830-

39. Rubin B.P., Schuetze S.M., Eary J.F., Norwood T.H., Mirza S., Conrad E.U., Molecular targeting of platelet-derived growth factor B by Imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol (2002) 20 : pp 3586-3591.

40. National Institutes of Health. Imatinib mesylate in treating patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblastoma. Retrieved Fevruary 5, 2008. Website: http://www.clinicaltrials.gov/ct/show/NCT00085475?order=1.

41. National Institutes of Health. Imatinib mesylate in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP. Retrieved February 5, 2008. Website: http://www.clinicaltrials.gov/ct/show/NCT00084630?order=1.

42. National Institutes of Health. Neoadjuvant Imatinib in Dermatofibrosarcoma Protuberans.  Retrieved September 29th 2012. Website: http://clinicaltrials.gov/ct2/show/results/NCT00243191?term=dfsp&rank=4&sect=X6015#outcome1.

43.  Jain S, Xu R, Prieto VG, Lee P,  Molecular classification of soft tissue sarcomas and its clinical applications Int J Clin Exp Pathol Apr 2010;3(4):416-429.

44.  Dagan R, Morris CG, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol. 2005 Dec;28(6):537-9.

45.  Haas RLM, Keus RB, Loftus BM, Rutgers EJTh, van Coevorden F, H. Bartelink H. The Role: of Radiotherapy in the Local Management of Dermatofibrosarcoma Protuberans EurJ Cancer, 1997 Vol. 33, .No. 7, pp. 1055-1060.

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 Mar 1;40(4):823-7.

47.  Rutgers EJ, Kroon BR, Albus-Lutter LE, et al: Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol 1992; 18:241-248.

48.  Snow S, 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 literature. Cancer. 2004;101:28- 38.

Print it

Dermatofibrosarcoma Protuberans (DFSP): An Update on Molecularly Targeted Therapy of Advanced Cases

Introduction

Update Figure 1

Figure 1: Pathological image of dermatofibrosarcoma protuberans...

Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor (comprising approximately 1% of soft tissue sarcomas) with typically indolent growth over years and a probability of regional/distant metastases of less than 2-3%.1,2 The disease most commonly affects adults aged 20-50 years. The estimated incidence of DFSP is 3 to 4.2 cases per million people per year, with equal sexual distribution.3,4 In DFSP harboring areas of high-grade fibrosarcoma (called fibrosarcomatous DFSP or DFSP-FS) metastases develop in the range of 8-15%,5,7 which is evidence of its more aggressive behavior. Distant metastases are usually localized in the lungs and less commonly in the lymph nodes. The standard treatment of this cutaneous sarcoma is radical, wide local excision; however a high rate of local control is also reported with the application of Mohs micrographic surgery.8 Since achieving negative margins is critical to prevent local relapse, the recommended margin of surgical excision is usually above 2 cm.1 Radical surgery often requires the use of reconstructive techniques and may result in cosmetic disfigurement or functional impairment. Such mutilating procedures might be avoided if appropriate Mohs micrographic surgery can be applied.9 If radical resection is not feasible, radiotherapy may be applied to reduce the risk of local recurrence. The dose of radiotherapy varies within the range of 50-70 Gy.10 Overall, local recurrences have been reported in the range of 24-90%.1,11

Molecular Biology

Almost all cases of DFSP are characterized by the distinctive reciprocal rearrangement of chromosomes 17 and 22 in the form of translocation t(17;22)(q22;q13) and often a supernumerary ring chromosome.12-16 This rearrangement results in the fusion of collagen type I a1 chain gene (COL1A1) to the platelet-derived growth factor (PDGF) B-chain gene (PDGFB). This COL1A1-PDGFB fusion may be identified in virtually all DFSP cases by sensitive molecular diagnostic tests: the fluorescence in-situ (FISH) method or multiplex reverse transcription polymerase chain reaction (RT-PCR), which is extremely important for differential diagnosis of atypical, metastatic DFSP or DFSP-FS.17,18 The consequences of these molecular events include the deregulation of PDGFB chain expression, the unscheduled expression of COL1A1/PDGFB fusion protein processing to mature homodimer PDGF-BB, and the continuous autocrine activation of PDGFR receptor B (PDGFRB), which is protein tyrosine kinase acting as a potent growth factor.19-21 The rearranged PDGF gene leads to the production of functional platelet-derived growth factor that can bind to and activate platelet-derived growth factor receptors on tumor cells, providing an autocrine and/or paracrine mitogenic stimulus, leading to malignant transformation.22 In some cases of DFSP with no evidence of the 17;22 chromosomal translocation, other molecular abnormalities were shown, such as t(5;8).23

FISH

Fluorescence in situ hybridization (FISH) is a laboratory technique used to detect a specific segment of DNA and its copies in a cell. The method can also identify structurally abnormal chromosomes. Specific segment of DNA is chemically modified and labeled in the laboratory so that it will become fluorescent under a special microscope. This DNA serves as a probe that can find matching segments of DNA.

Clinical Results

Advances in the understanding of the molecular mechanisms of DFSP have resulted in the introduction of targeted therapy acting on PDGFR to clinical practice. Imatinib mesylate is a tyrosine kinase inhibitor specifically directed toward BCR/ABL, KIT, FMS (the receptor for Colony Stimulating Factor 1), ARG (ABL-related gene) and PDGFR alpha and beta. It is an effective systemic therapy in most cases of DFSP. Imatinib competes with the adenosine triphosphate (ATP) molecule, blocking the tyrosine kinase receptor’s ability for autophosporylation, which results in inhibition of the damaged pathway of signal transduction and restoration of proper intracellular signaling.

Imatinib

A small molecule inhibitor that targets several tyrosine kinases including the Abelson leukemia (ABL) kinase, KIT, PDGFR, ARG and FMS. It is used to treat patients with chronic myelogenous leukemia, gastrointestinal stromal tumors and myeloproliferative diseases with translocations involving PRGFR genes. Imatinib mesylate (Glivec®) is administered orally, and the dose of 400-800 mg daily is recommended.

The observation that autocrine overproduction of PDGFB from gene rearrangement is a key pathogenetic factor19,20 and provoked the in vitro research, which showed inhibition of DFSP cell growth after exposure to imatinib mesylate.22,24 The further demonstration of the inhibitory effect of imatinib on six different DFSP cell lines in vitro and in vivo25 led to the investigation of this new therapeutic approach in the clinic. The first reports on six patients suggested the usefulness of imatinib in metastatic and locally advanced DFSP.26-31 The next series of ten patients with locally advanced and/or metastatic DFSP treated in the Imatinib Target Exploration Consortium Study B2225 showed 100% response rate (50% were complete responses) in locally advanced cases and one partial response lasting seven months in the metastatic setting.32 These observations resulted in imatinib’s registration as the therapy of choice in inoperable and/or metastatic DFSP. In a phase II trial33 evaluating the activity of imatinib in life-threatening malignancies expressing imatinib-sensitive tyrosine kinase, DFSP was the only one out of five tumor types where notable activity was shown with extensive regression in ten of twelve cases (50% partial remissions, 33.3% complete remissions).

Combined analysis of two prematurely closed phase II, single arm, open-label trials (European Organisation for Research and Treatment of Cancer no. 62027 and the Southwest Oncology Group no. S0345) regarding the efficacy of imatinib in advanced (inoperable and/or metastatic) DFSP has demonstrated a clinical benefit rate exceeding 70% for twenty-five patients with advanced DFSP, with median time to progression of 1.7 years.34 Another study35 on fifteen patients who did not qualify for clinical trials has proven the striking activity of imatinib mesylate in advanced DFSP, with clinical benefit rate approaching 80% as well as median Progression Free Survival (PFS) and Overall Survival (OS) were not reached. It has been shown that DFSP-FS is also sensitive to imatinib, although responses seem to be shorter in duration.36 DFSP-FS tumors lacking the 17;22 chromosomal translocation32 do not respond to imatinib. The presence of a molecular target (COL1A1-PDGFB) is obligatory to confirm diagnosis of DFSP in every case prior to the start of imatinib therapy.

Update Figure 2

Figure 2A-B: Images of advanced DFSP before and after therapy...

Given the fact that complete, wide surgical excision is the standard treatment in localized resectable DFSP cases, neoadjuvant imatinib therapy leading to tumor downstaging and less cosmetic disfigurement, functional impairment and excision morbidity appears very attractive. Lebbe et al.37 presented a preliminary report on twenty-five resectable DFSP (median size – 4.5 cm) treated in a phase II trial with preoperative imatinib at the dose of 600 mg. daily. Objective partial response according to RECIST was observed in nine cases (36%). Present results indicate that some DFSP cases initially evaluated as unresectable/metastatic or necessitating disfiguring surgery were evaluated as resectable after imatinib therapy. This rational approach leading to complete remission may be potentially curative, although longer follow-up is needed. Further studies are necessary for elucidating whether preoperative imatinib therapy reduces the need for wide surgical margins or whether imatinib has activity as adjuvant therapy in cases of positive margins after excision or in other high-risk patients.

Update Figure 3

Figure 3: Computed tomography scans before (left) and after (right)...

The dose of imatinib used in mentioned studies ranged from 400 to 800 mg. daily. Available clinical data are not sufficient to determine the optimal dose of initial imatinib treatment, since objective responses were observed both with lower and higher dosing schedules.

The majority of patients treated with imatinib experience side effects during treatment, but almost all are mild and manageable; the most common being fluid retention/edema, anemia, fatigue, nausea, skin rash, thrombocytopenia, vomiting, neutropenia and diarrhea.33

Future Directions

There is still uncertainty concerning the mechanisms of imatinib action and resistance in the treatment of DFSP, as well as a need to identify novel molecular markers predicting response to such therapy. It was presumed that imatinib’s effect resulted from the inhibition of phosphorylation of PDGFR. Unexpectedly, the clinical activity of imatinib is striking even in DFSP that expresses a relatively low amount of activated PDGFRB. If tumor cells are dependent on that signaling mechanism, it seems that the inhibition of low-level receptor tyrosine kinases may still be clinically effective.

Summary

Imatinib is currently the gold standard therapy of inoperable, metastatic, or recurrent cases of DFSP. Such treatment may potentially facilitate resection or decrease disfigurement related to an extensive surgical procedure. A significant percentage of patients may be rendered free of disease by excision of residual disease following partial response on imatinib. Current therapy of DFSP with the 17;22 chromosomal translocation should be definitively conducted by a multidisciplinary team, including an oncological surgeon. The use of imatinib mesylate as initial therapy to decrease the extent of wide surgical resection and related morbidity should be always considered.

Last revision and medical review: 06/2011

By Piotr Rutkowski, MD, PhD
and Tomasz Switaj, MD, PhD
Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology
Department of Soft Tissue/Bone Sarcoma and Melanoma in Warsaw, Poland

References and Bibliography

1 . Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol 2004; 30:341-345. 

2. Laskin WB. Dermatofibrosarcoma protuberans. Ca Cancer J Clin 1992; 42:116-125. 

3. 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(1):95-98. 

4. Monnier D, Vidal C, Martin L, et al. Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002. J Eur Acad Dermatol Venereol 2006; 20(10):1237-42. 

5. Bowne WB, Antonescu CR, Leung DHY, et al. Dermatofibrosarcoma protuberans. A clinicopathological analysis of patients treated and followed at a single institution. Cancer 2000; 88:2711-2720. 

6. Mentzel T, Beham A, Katenkamp D, et al. Fibrosarcomatous ‘high-grade’ dermatofibrosarcoma protuberans: clinicopathological and immunohistochemical study of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998; 22:576-587. 

7. Lal P, Sharma R, Mohan H, Sekhon MS. Dermatofibrosarcoma protuberans metastasizing to lymph nodes: a case report and review of literature. J Surg Oncol 1999; 72:178-180. 

8. Meguerditchian AN, Wang J, Lema B, et al. Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 2010; 33(3):300-303. 

9. A. Stojadinovic, H. M. Karpoff, C. R. Antonescu, et al. "Dermatofibrosarcoma protuberans of the head and neck," Annals of Surgical Oncology 2000; 7:696-704. 

10. Dagan R, Morris CG, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 2005; 28(6):537-9. 

11. S. Ten Heuvel, A. Suurmeijer, E. Pras, R. J. Van Ginkel, H. J. Hoekstra, "Dermatofibrosarcoma protuberans: Recurrence is related to the adequacy of surgical margins," European Journal of Surgical Oncology 2010; 36:89-94. 

12. Pédeutour F, Coindre J-M, Sozzi G, et al. Supernumerary ring chromosomes containing chromosome 17 sequences: a specific feature of dermatofibrosarcoma protuberans? Cancer Genet Cytogenet 1994; 76:1–9. 

13. Pédeutour F, Simon MP, Minoletti F, et al. Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement. Cytogenet Cell Genet 1996; 72: 171-4. 

14. 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: 1-12.

15. Simon M-P, Navarro M, Roux D, Pouysségur J. Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in dermatofibrosarcoma protuberans (DP). Oncogene 2001; 20: 2965-75.

16. Patel KU, Szabo SS, Hernandez VS, et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. Hum Pathol 2008; 39, 184–193. 

17. Kerob D, Pedeutour F, Leboeuf C, et al. Value of Cytogenetic Analysis in the Treatment of Dermatofibrosarcoma Protuberans. J Clin Oncol 2008; 26:1757-9. 

18. Wang J, Morimutsu Y, Okamoto S et al: COL1A1-PDGFB fusion transcript in fibrosarcomatous areas of six dermatofibrosarcoma protuberans. J Mol Diag 2000; 2: 47-52.

19. Shimizu A, O’Brien KP, Sjöblom T, et al. The dermatofibrosarcoma protuberans-associated collagen type I_1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGFBB. Cancer Res 1999; 59:3719-3723. 

20. Simon M-P, Navarro M, Roux D, et al. Transforming properties of chimerical protein COL1A1-PDGFB generated by dermatofibrosarcoma protuberans-associated translocation t(17;22)(q22;q13.1). Cancer Genet Cytogenet 2001;128: 82. 

21. McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol 2004; 31: 30-36. 

22. 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; 17:1313-1319. 

23. Bianchini L, Maire G, Guillot B, et al. Complex t(5;8) involving the CSPG2 and PTK2B genes in a case of dermatofibrosarcoma protuberans without the COL1A1-PDGFB fusion. Virchows Arch 2008; 452(6):689-96. 

24. 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: 5778–5783. 

25. Greco A, Roccato E, Miranda C, et al: Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGF-beta rearrangement. Int J Cancer 2001; 92:354-60.

26. Maki RG, Awan RA, Dixon RH, et al. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer 2002; 100: 623-6. 

27. 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: 3586-3591. 

28. Pedeutour F, Coindre JM, Nicolo G, et al. Response of metastatic dermatofibrosarcoma protuberans to imatinib mesylate. Proc Am Soc Clin Oncol 2003 ; 23(abstr 3334). 

29. Ruka W, Falkowski S, Wudarska J, et al.. The partial response of lung metastases arising from dermatofibrosarcoma after one month of imatinib therapy – a case report. Nowotwory – Journal of Oncology 2003; 53:165-168. 

30. Labropoulos SV, Fletcher JA, Oliveira AM, et al. Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs 2005; 16: 461-6. 

31. 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: 235-7. 

32. McArthur GA, Demetri GD, van Oosterom AT, 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: 866-873. 

33. Heinrich MC, Joensuu H, Demetri GD, et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clin Cancer Res 2008; 14, 2717-25. 

34. Rutkowski P, Van Glabbeke M, Rankin CJ, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans (DFSP): pooled analysis of two phase II clinical trials. J Clin Oncol 2010; 28: 1772-1779.

35. Rutkowski P, Dębiec-Rychter M, Nowecki ZI, Michej W, Symonides M, Ptaszynski K, Ruka W. Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection. J Eur Acad Dermatol Venereol. 2010 Jun 21. [Epub ahead of print] 

36. Gronchi A, Stacchiotti S, Pedeutour F, et al. Response to imatinib mesylate (IM) in fibrosarcoma (FS) arising in dermatofibrosarcoma protuberans (DFSP). J Clin Oncol 2008; 26, (suppl; abstr 10593). 

37. Lebbé C, Kerob D, Porcher R et al:. Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: Results of a multicentric phase II study on 25 patients. J Clin Oncol 2007; 25: 18s, (suppl; abstr 10032).

Dermatofibrosarcoma Protuberans Stories and Support

Sigridur shares her story

Sigridur with her husband

I am a biomedical scientist, am married and have three boys (15, 22 and 24). I have been very healthy and active all my life. Together with my family I have travelled a lot, and we often go swimming, skiing, diving, and hiking.

Today I am a very different person than before the sarcoma. Of course life changes us all, but this kind of experience pushes you very quickly and roughly through those changes. At times I have experienced a kind of grief over the loss of "old me." It has been so difficult to make a new life with new routines. Not only are my physical capabilities not the same, but my values and longings have also changed so much. Now I live in the moment, enjoying the smallest things I used to take for granted. I follow my instinct more when making decisions and work all the time on making my life simpler. This has made me calmer and happier, and I have a clear image of myself and what I stand for. There really is nothing I cannot do, I just have to be clear about what I want to do. Read more.

Tammi writes about her experience

Tammi and her dog

I was a happy go lucky person. My life revolved around work basically, anything from 48-60 hours a week. I played the occasional hockey game and loved the thrill of riding my motorbikes. Then all a sudden, my life changed. I had a lump in between my shoulder blades; it had been there several years. I saw a doctor several times and a nurse about my concerns for it, and they all told me it was a harmless cyst.

...Having cancer has made me discover there is more to life than work. I have enrolled again in higher education doing photography, which is a huge passion of mine. I have ticked New York City off my bucket list as well. I am now going to treat life as a gift. Do everything possible, live it with some freedom, "Live each day as it is, it will never come round again." Read more.

Will you share your story?

We would like to fill this page with personal stories that offer hope and encouragement to everyone learning about DFSP. Please consider sharing your story.

Connect on Facebook

Here are a few of our favorite Facebook groups that provide opportunities to exchange messages with DFSP patients and their families.

Find treatment and support resources

We maintain listings of sarcoma treatment centers, local support groups and organizations that provide financial assistance to sarcoma patients and their loved-ones.

  • Figure 1: Photograph of DFSP.
    Note the dark-red thickened appearance (courtesy of Donald Rudikoff, MD, Albert Einstein College of Medicine, Department of Dermatology).
  • Figure 2: An advanced, large fungating DFSP
    An advanced, large fungating DFSP overlying the anteromedial aspect of the distal leg.
  • Figure 3: DFSP composed of slender fibroblasts arranged in a storiform pattern.
  • Figure 4: Extensive positivity is typically seen with CD34 staining.
  • Figure 5: Preoperative photograph
    Preoperative photograph showed planned surgical margin for resection of tumor.
  • Figure 6: Intraoperative photograph
    Intraoperative photograph showing resection of the tumor with a large area of exposed bone and muscle. Resection is carried down to perisoteum and fascia due to large and deep nature of this tumor. Most tumors present as much smaller masses and do not require such extensive resections.
  • Figure 7: Postoperative photograph
    Postoperative photograph showing alloderm placement over the large defect. Alloderm offers immediate coverage over bone and tendon and is eventually replaced by host tissue, much as in the case of allograft bone grafting. Once granulation tissue covers the alloderm, a split-thickness skin graft can be performed. This obviates the donor site morbidity associated with more-involved coverage procedures and offers excellent cosmesis as well.
  • Update Figure 1
    Pathological image of dermatofibrosarcoma protuberans with CD34-immunostaining, showing a characteristic storiform pattern of spindle cells with mild atypia.
  • Update Figure 2A: Before Treatment
    Figure 2: Images of advanced dermatofibrosarcoma protuberans of the back before and after therapy with imatinib.
  • Update Figure 2B: After Treatment
    Figure 2: Images of advanced dermatofibrosarcoma protuberans of the back before and after therapy with imatinib.
  • Update Figure 3A: Before treatment
    Figure 3: Computed tomography scans before and after three months of imatinib therapy, demonstrating the response of FS-DFSP intrathoracic metastases.
  • Update Figure 3B: After treatment
    Figure 3: Computed tomography scans before and after three months of imatinib therapy, demonstrating the response of FS-DFSP intrathoracic metastases.