A 55-year-old African American male presented with a 2-year history of a slow-growing, non-tender growth on his back. The lesion was treated as a hypertrophic scar with several injections of intralesional triamcinolone without improvement. The patient reported a rapid growth of the lesion in the 6 months prior to presentation. His past medical history was unremarkable. He has no past history of cutaneous malignancies or disorders of the skin.
On physical examination there was a firm red-brown fixed lesion with an irregular surface and asymmetrical borders measuring approximately 8.5 cm x 7.5 cm on the patient’s left upper back (Figure 1). The area was non-tender and there was no exudate or ulceration outside of the suture areas from previous biopsy.
What is Your Diagnosis?
See below for an answer and for more details.
Diagnosis:
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue tumor with a tendency to recur after excision. The estimated incidence is 4.2 to 4.5 cases per million each year in the United States, representing 0.1% of all malignancies.1-3 It commonly presents between age 30 and 50, although cases have been described in all age groups as well as congenital.3,4 The tumor demonstrates a racial predilection, with a greater incidence in African Americans than Caucasians.1
The etiology of DFSP is unknown. Reports have demonstrated that there is a relation to cutaneous trauma, including prior scars, burns, irradiated areas, as well as sites of tattoos.5,6 More than 90% of cases of DFSP have been associated with a specific chromosome translocation, t(17;22)(q22;q13). This translocation causes fusion of collagen, type 1 alpha 1 and platelet-derived growth factor-B (PDGFB), leading to increased production of growth factor and thus increased cellular proliferation.3,5,7
Clinical Presentations
DFSP often begins as an asymptomatic slow-growing nodule or plaque that is skin-colored or red to blue (Figure 1).
Figures 1. 8.5 cm x 7.5 cm nodule on the patient’s left upper back.
The tumor gradually enlarges and is locally destructive, often infiltrating surrounding fascia, muscle and bone.3,8 In advanced disease, the tumor may be characterized by ulceration, pain and bleeding. DFSP has the ability to metastasize hematogenously, although this is rare (1%-4%).8,9 Large tumor size and prolonged time for adequate diagnosis is common due to the tumor’s initial indolent appearance.10 DFSP most commonly occurs on the trunk (about 50%), followed by proximal extremities (25%-30%) and head and neck (10%-15%).3,8
DFSP has several variants. Bednar tumor is an uncommon pigmented variant in which the cells contain melanin.5 Giant cell fibroblastoma is considered a juvenile form of DFSP.4 Fibrosarcomatous DFSP is the transformation of DFSP to a more aggressive form with a greater potential for metastasis.5,8
Histopathology
Diagnosis is usually made by biopsy with examination of hematoxylin and eosin stained specimens under light microscopy.10 Histologically, DFSP can be identified by uniform proliferation of dermal spindle cells in a characteristic cartwheel or storiform pattern, with fingerlike projections into the deep dermis, underlying fat and other nearby tissues.3,5,11 The cells exhibit a low mitotic index and relatively low amounts of pleomorphism.3,8
DFSP can be further identified by immunohistochemistry in the event of an uncertain diagnosis, especially when differentiating it from a dermatofibroma. DFSP is positive for CD34 and stromolysin-3, but negative for Factor XIIIa.3,5,12 In contrast, dermatofibroma is usually negative for CD34 and positive for Factor XIIIa.3 The sensitivity of CD34 for DFSP is between 84% and 100%.3
Differential Diagnosis
Misdiagnosis and delay in diagnosis of DFSP is common. Small-sized DFSP may be difficult to clinically distinguish from a dermatofibroma, especially the cellular and deep variant.5 Other fibrous tumors, such as fibrosarcoma, atypical fibroxanthoma and nodular fasciitis should be considered.3 DFSP may also resemble a hypertrophic scar or keloid, or have a vascular appearance similar to a hemangioma.4,12 Other diagnostic considerations include neurofibroma, epidermal inclusion cysts, melanoma or metastatic cutaneous malignancy.4
Management
The National Comprehensive Cancer Network recommends diagnosis with biopsy, with re-biopsy if clinical suspicion is high following an initial negative biopsy.10
Once the diagnosis is confirmed, the initial treatment of DFSP is surgical. Achievement of adequate margins is critical due to high local recurrence secondary to the tumor’s infiltrative growth. Although not uniformally accepted by all authors, many recommend that Mohs micrographic surgery as the treatment of choice, with a recurrence rate around 1%.3,9 The recurrence rate following management with wide local excision (3 cm margins) is between 10% and 20%.11
Resection of DFSP often leads to large defects that may require reconstruction.11 Negative margins should be confirmed prior to reconstruction. Flaps provide superior cosmetic results compared to skin grafts, and tissue expansion may be needed for further esthetic considerations, especially for lesions on the face, head or neck.9,11
Molecular therapy with imatinib (Gleevec, Novartis), a PDGFB tyrosine kinase inhibitor, has been shown effective in treating DFSP with the t(17;22)(q22;q13) translocation. It is FDA approved to treat unresectable, recurrent or metastatic DFSP in adults.10 Drug resistance with imatinib has been described.7 Further, sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.), a B-Raf and vascular endothelial growth factor receptor inhibitor, has been reported to be efficacious in a case of DFSP that failed conventional therapy.8
DFSP is considered a radiosensitive tumor. Adjuvant radiotherapy is not necessary with clear surgical margins, but should be considered for unresectable or recurrent disease.10
Clinical follow-up is recommended due to a high rate of recurrence. An estimated 50% of recurrences occur within the first year post-excision, and 80% within 3 years.5,9
Our Patient
Pathologic evaluation of the biopsy specimen showed proliferation of spindle cells in a storiform pattern with downward projections into the deep dermis, consistent with dermatofibrosarcoma protuberans (Figure 2). The patient was educated on available treatment options including Mohs micrographic surgery and imatinib. The patient elected to undergo tumor removal using Mohs surgery. After negative margins were obtained, the repair of the defect was performed by plastic surgery. At 6 months follow-up, the patient demonstrated a well-healed surgical scar and no recurrence of local disease.
Figure 2. Proliferation of dermal spindle cells in a storiform pattern, with projections into the deep dermis.
Conclusion
Dermatofibrosarcoma protuberans is a rare, locally aggressive soft tissue tumor that often presents as an asymptomatic slow-growing nodule or plaque. Delay in diagnosis is common due to its initial benign appearance. Etiology is unknown but may be related to prior tissue trauma.
The mainstay of treatment is with surgical excision, preferentially Mohs micrographic surgery. Clear margins should be obtained, as local recurrence is common. Adjunct therapy with imatinib and/or radiation is recommended for recurrent or unresectable tumors.
Ms. Marchionne is a fourth-year medical student at the University of Nevada School of Medicine in Las Vegas, NV.
Dr. Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at the State University of New York Downstate in Brooklyn, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56(6):968-973.
2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S.: an analysis of 12,114 cases. Cancer. 2008;113(3):616-627.
3. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012;38(4):537-551.
4. Checketts SR, Hamilton TK, Baughman RD. Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature. J Am Acad Dermatol. 2000;42(5 Pt 2):907-913.
5. Akram J, Wooler G, Lock-Andersen J. Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines. J Plast Surg Hand Surg. 2014;48(1):67-73.
6. Reddy KK, Hanke CW, Tierney EP. Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature. J Drugs Dermatol. 2011;10(8):837-842.
7. Hong JY, Liu X, Mao M, et al. Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PLoS One. 2013;8(7):e69752.
8. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3(1):5.
9. Goldberg C, Hoang D, McRae M, Chung C, Leffell DJ, Narayan D. A strategy for the successful management of dermatofibrosarcoma protuberans. Ann Plast Surg. Published online ahead of print June 19, 2013.
10. Miller SJ, Alam M, Anderson JS, et al. Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw. 2012;10(3):312-318.
11. Khachemoune A, Barkoe D, Braun M, Davison SP. Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: multistaged repair with the use of skin expanders. Dermatol Surg. 2005;31(1):115-119.
12. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28.
A 55-year-old African American male presented with a 2-year history of a slow-growing, non-tender growth on his back. The lesion was treated as a hypertrophic scar with several injections of intralesional triamcinolone without improvement. The patient reported a rapid growth of the lesion in the 6 months prior to presentation. His past medical history was unremarkable. He has no past history of cutaneous malignancies or disorders of the skin.
On physical examination there was a firm red-brown fixed lesion with an irregular surface and asymmetrical borders measuring approximately 8.5 cm x 7.5 cm on the patient’s left upper back (Figure 1). The area was non-tender and there was no exudate or ulceration outside of the suture areas from previous biopsy.
What is Your Diagnosis?
Diagnosis:
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue tumor with a tendency to recur after excision. The estimated incidence is 4.2 to 4.5 cases per million each year in the United States, representing 0.1% of all malignancies.1-3 It commonly presents between age 30 and 50, although cases have been described in all age groups as well as congenital.3,4 The tumor demonstrates a racial predilection, with a greater incidence in African Americans than Caucasians.1
The etiology of DFSP is unknown. Reports have demonstrated that there is a relation to cutaneous trauma, including prior scars, burns, irradiated areas, as well as sites of tattoos.5,6 More than 90% of cases of DFSP have been associated with a specific chromosome translocation, t(17;22)(q22;q13). This translocation causes fusion of collagen, type 1 alpha 1 and platelet-derived growth factor-B (PDGFB), leading to increased production of growth factor and thus increased cellular proliferation.3,5,7
Clinical Presentations
DFSP often begins as an asymptomatic slow-growing nodule or plaque that is skin-colored or red to blue (Figure 1).
Figures 1. 8.5 cm x 7.5 cm nodule on the patient’s left upper back.
The tumor gradually enlarges and is locally destructive, often infiltrating surrounding fascia, muscle and bone.3,8 In advanced disease, the tumor may be characterized by ulceration, pain and bleeding. DFSP has the ability to metastasize hematogenously, although this is rare (1%-4%).8,9 Large tumor size and prolonged time for adequate diagnosis is common due to the tumor’s initial indolent appearance.10 DFSP most commonly occurs on the trunk (about 50%), followed by proximal extremities (25%-30%) and head and neck (10%-15%).3,8
DFSP has several variants. Bednar tumor is an uncommon pigmented variant in which the cells contain melanin.5 Giant cell fibroblastoma is considered a juvenile form of DFSP.4 Fibrosarcomatous DFSP is the transformation of DFSP to a more aggressive form with a greater potential for metastasis.5,8
Histopathology
Diagnosis is usually made by biopsy with examination of hematoxylin and eosin stained specimens under light microscopy.10 Histologically, DFSP can be identified by uniform proliferation of dermal spindle cells in a characteristic cartwheel or storiform pattern, with fingerlike projections into the deep dermis, underlying fat and other nearby tissues.3,5,11 The cells exhibit a low mitotic index and relatively low amounts of pleomorphism.3,8
DFSP can be further identified by immunohistochemistry in the event of an uncertain diagnosis, especially when differentiating it from a dermatofibroma. DFSP is positive for CD34 and stromolysin-3, but negative for Factor XIIIa.3,5,12 In contrast, dermatofibroma is usually negative for CD34 and positive for Factor XIIIa.3 The sensitivity of CD34 for DFSP is between 84% and 100%.3
Differential Diagnosis
Misdiagnosis and delay in diagnosis of DFSP is common. Small-sized DFSP may be difficult to clinically distinguish from a dermatofibroma, especially the cellular and deep variant.5 Other fibrous tumors, such as fibrosarcoma, atypical fibroxanthoma and nodular fasciitis should be considered.3 DFSP may also resemble a hypertrophic scar or keloid, or have a vascular appearance similar to a hemangioma.4,12 Other diagnostic considerations include neurofibroma, epidermal inclusion cysts, melanoma or metastatic cutaneous malignancy.4
Management
The National Comprehensive Cancer Network recommends diagnosis with biopsy, with re-biopsy if clinical suspicion is high following an initial negative biopsy.10
Once the diagnosis is confirmed, the initial treatment of DFSP is surgical. Achievement of adequate margins is critical due to high local recurrence secondary to the tumor’s infiltrative growth. Although not uniformally accepted by all authors, many recommend that Mohs micrographic surgery as the treatment of choice, with a recurrence rate around 1%.3,9 The recurrence rate following management with wide local excision (3 cm margins) is between 10% and 20%.11
Resection of DFSP often leads to large defects that may require reconstruction.11 Negative margins should be confirmed prior to reconstruction. Flaps provide superior cosmetic results compared to skin grafts, and tissue expansion may be needed for further esthetic considerations, especially for lesions on the face, head or neck.9,11
Molecular therapy with imatinib (Gleevec, Novartis), a PDGFB tyrosine kinase inhibitor, has been shown effective in treating DFSP with the t(17;22)(q22;q13) translocation. It is FDA approved to treat unresectable, recurrent or metastatic DFSP in adults.10 Drug resistance with imatinib has been described.7 Further, sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.), a B-Raf and vascular endothelial growth factor receptor inhibitor, has been reported to be efficacious in a case of DFSP that failed conventional therapy.8
DFSP is considered a radiosensitive tumor. Adjuvant radiotherapy is not necessary with clear surgical margins, but should be considered for unresectable or recurrent disease.10
Clinical follow-up is recommended due to a high rate of recurrence. An estimated 50% of recurrences occur within the first year post-excision, and 80% within 3 years.5,9
Our Patient
Pathologic evaluation of the biopsy specimen showed proliferation of spindle cells in a storiform pattern with downward projections into the deep dermis, consistent with dermatofibrosarcoma protuberans (Figure 2). The patient was educated on available treatment options including Mohs micrographic surgery and imatinib. The patient elected to undergo tumor removal using Mohs surgery. After negative margins were obtained, the repair of the defect was performed by plastic surgery. At 6 months follow-up, the patient demonstrated a well-healed surgical scar and no recurrence of local disease.
Figure 2. Proliferation of dermal spindle cells in a storiform pattern, with projections into the deep dermis.
Conclusion
Dermatofibrosarcoma protuberans is a rare, locally aggressive soft tissue tumor that often presents as an asymptomatic slow-growing nodule or plaque. Delay in diagnosis is common due to its initial benign appearance. Etiology is unknown but may be related to prior tissue trauma.
The mainstay of treatment is with surgical excision, preferentially Mohs micrographic surgery. Clear margins should be obtained, as local recurrence is common. Adjunct therapy with imatinib and/or radiation is recommended for recurrent or unresectable tumors.
Ms. Marchionne is a fourth-year medical student at the University of Nevada School of Medicine in Las Vegas, NV.
Dr. Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at the State University of New York Downstate in Brooklyn, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56(6):968-973.
2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S.: an analysis of 12,114 cases. Cancer. 2008;113(3):616-627.
3. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012;38(4):537-551.
4. Checketts SR, Hamilton TK, Baughman RD. Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature. J Am Acad Dermatol. 2000;42(5 Pt 2):907-913.
5. Akram J, Wooler G, Lock-Andersen J. Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines. J Plast Surg Hand Surg. 2014;48(1):67-73.
6. Reddy KK, Hanke CW, Tierney EP. Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature. J Drugs Dermatol. 2011;10(8):837-842.
7. Hong JY, Liu X, Mao M, et al. Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PLoS One. 2013;8(7):e69752.
8. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3(1):5.
9. Goldberg C, Hoang D, McRae M, Chung C, Leffell DJ, Narayan D. A strategy for the successful management of dermatofibrosarcoma protuberans. Ann Plast Surg. Published online ahead of print June 19, 2013.
10. Miller SJ, Alam M, Anderson JS, et al. Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw. 2012;10(3):312-318.
11. Khachemoune A, Barkoe D, Braun M, Davison SP. Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: multistaged repair with the use of skin expanders. Dermatol Surg. 2005;31(1):115-119.
12. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28.
A 55-year-old African American male presented with a 2-year history of a slow-growing, non-tender growth on his back. The lesion was treated as a hypertrophic scar with several injections of intralesional triamcinolone without improvement. The patient reported a rapid growth of the lesion in the 6 months prior to presentation. His past medical history was unremarkable. He has no past history of cutaneous malignancies or disorders of the skin.
On physical examination there was a firm red-brown fixed lesion with an irregular surface and asymmetrical borders measuring approximately 8.5 cm x 7.5 cm on the patient’s left upper back (Figure 1). The area was non-tender and there was no exudate or ulceration outside of the suture areas from previous biopsy.
What is Your Diagnosis?
,
A 55-year-old African American male presented with a 2-year history of a slow-growing, non-tender growth on his back. The lesion was treated as a hypertrophic scar with several injections of intralesional triamcinolone without improvement. The patient reported a rapid growth of the lesion in the 6 months prior to presentation. His past medical history was unremarkable. He has no past history of cutaneous malignancies or disorders of the skin.
On physical examination there was a firm red-brown fixed lesion with an irregular surface and asymmetrical borders measuring approximately 8.5 cm x 7.5 cm on the patient’s left upper back (Figure 1). The area was non-tender and there was no exudate or ulceration outside of the suture areas from previous biopsy.
What is Your Diagnosis?
See below for an answer and for more details.
Diagnosis:
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue tumor with a tendency to recur after excision. The estimated incidence is 4.2 to 4.5 cases per million each year in the United States, representing 0.1% of all malignancies.1-3 It commonly presents between age 30 and 50, although cases have been described in all age groups as well as congenital.3,4 The tumor demonstrates a racial predilection, with a greater incidence in African Americans than Caucasians.1
The etiology of DFSP is unknown. Reports have demonstrated that there is a relation to cutaneous trauma, including prior scars, burns, irradiated areas, as well as sites of tattoos.5,6 More than 90% of cases of DFSP have been associated with a specific chromosome translocation, t(17;22)(q22;q13). This translocation causes fusion of collagen, type 1 alpha 1 and platelet-derived growth factor-B (PDGFB), leading to increased production of growth factor and thus increased cellular proliferation.3,5,7
Clinical Presentations
DFSP often begins as an asymptomatic slow-growing nodule or plaque that is skin-colored or red to blue (Figure 1).
Figures 1. 8.5 cm x 7.5 cm nodule on the patient’s left upper back.
The tumor gradually enlarges and is locally destructive, often infiltrating surrounding fascia, muscle and bone.3,8 In advanced disease, the tumor may be characterized by ulceration, pain and bleeding. DFSP has the ability to metastasize hematogenously, although this is rare (1%-4%).8,9 Large tumor size and prolonged time for adequate diagnosis is common due to the tumor’s initial indolent appearance.10 DFSP most commonly occurs on the trunk (about 50%), followed by proximal extremities (25%-30%) and head and neck (10%-15%).3,8
DFSP has several variants. Bednar tumor is an uncommon pigmented variant in which the cells contain melanin.5 Giant cell fibroblastoma is considered a juvenile form of DFSP.4 Fibrosarcomatous DFSP is the transformation of DFSP to a more aggressive form with a greater potential for metastasis.5,8
Histopathology
Diagnosis is usually made by biopsy with examination of hematoxylin and eosin stained specimens under light microscopy.10 Histologically, DFSP can be identified by uniform proliferation of dermal spindle cells in a characteristic cartwheel or storiform pattern, with fingerlike projections into the deep dermis, underlying fat and other nearby tissues.3,5,11 The cells exhibit a low mitotic index and relatively low amounts of pleomorphism.3,8
DFSP can be further identified by immunohistochemistry in the event of an uncertain diagnosis, especially when differentiating it from a dermatofibroma. DFSP is positive for CD34 and stromolysin-3, but negative for Factor XIIIa.3,5,12 In contrast, dermatofibroma is usually negative for CD34 and positive for Factor XIIIa.3 The sensitivity of CD34 for DFSP is between 84% and 100%.3
Differential Diagnosis
Misdiagnosis and delay in diagnosis of DFSP is common. Small-sized DFSP may be difficult to clinically distinguish from a dermatofibroma, especially the cellular and deep variant.5 Other fibrous tumors, such as fibrosarcoma, atypical fibroxanthoma and nodular fasciitis should be considered.3 DFSP may also resemble a hypertrophic scar or keloid, or have a vascular appearance similar to a hemangioma.4,12 Other diagnostic considerations include neurofibroma, epidermal inclusion cysts, melanoma or metastatic cutaneous malignancy.4
Management
The National Comprehensive Cancer Network recommends diagnosis with biopsy, with re-biopsy if clinical suspicion is high following an initial negative biopsy.10
Once the diagnosis is confirmed, the initial treatment of DFSP is surgical. Achievement of adequate margins is critical due to high local recurrence secondary to the tumor’s infiltrative growth. Although not uniformally accepted by all authors, many recommend that Mohs micrographic surgery as the treatment of choice, with a recurrence rate around 1%.3,9 The recurrence rate following management with wide local excision (3 cm margins) is between 10% and 20%.11
Resection of DFSP often leads to large defects that may require reconstruction.11 Negative margins should be confirmed prior to reconstruction. Flaps provide superior cosmetic results compared to skin grafts, and tissue expansion may be needed for further esthetic considerations, especially for lesions on the face, head or neck.9,11
Molecular therapy with imatinib (Gleevec, Novartis), a PDGFB tyrosine kinase inhibitor, has been shown effective in treating DFSP with the t(17;22)(q22;q13) translocation. It is FDA approved to treat unresectable, recurrent or metastatic DFSP in adults.10 Drug resistance with imatinib has been described.7 Further, sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.), a B-Raf and vascular endothelial growth factor receptor inhibitor, has been reported to be efficacious in a case of DFSP that failed conventional therapy.8
DFSP is considered a radiosensitive tumor. Adjuvant radiotherapy is not necessary with clear surgical margins, but should be considered for unresectable or recurrent disease.10
Clinical follow-up is recommended due to a high rate of recurrence. An estimated 50% of recurrences occur within the first year post-excision, and 80% within 3 years.5,9
Our Patient
Pathologic evaluation of the biopsy specimen showed proliferation of spindle cells in a storiform pattern with downward projections into the deep dermis, consistent with dermatofibrosarcoma protuberans (Figure 2). The patient was educated on available treatment options including Mohs micrographic surgery and imatinib. The patient elected to undergo tumor removal using Mohs surgery. After negative margins were obtained, the repair of the defect was performed by plastic surgery. At 6 months follow-up, the patient demonstrated a well-healed surgical scar and no recurrence of local disease.
Figure 2. Proliferation of dermal spindle cells in a storiform pattern, with projections into the deep dermis.
Conclusion
Dermatofibrosarcoma protuberans is a rare, locally aggressive soft tissue tumor that often presents as an asymptomatic slow-growing nodule or plaque. Delay in diagnosis is common due to its initial benign appearance. Etiology is unknown but may be related to prior tissue trauma.
The mainstay of treatment is with surgical excision, preferentially Mohs micrographic surgery. Clear margins should be obtained, as local recurrence is common. Adjunct therapy with imatinib and/or radiation is recommended for recurrent or unresectable tumors.
Ms. Marchionne is a fourth-year medical student at the University of Nevada School of Medicine in Las Vegas, NV.
Dr. Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at the State University of New York Downstate in Brooklyn, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56(6):968-973.
2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S.: an analysis of 12,114 cases. Cancer. 2008;113(3):616-627.
3. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012;38(4):537-551.
4. Checketts SR, Hamilton TK, Baughman RD. Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature. J Am Acad Dermatol. 2000;42(5 Pt 2):907-913.
5. Akram J, Wooler G, Lock-Andersen J. Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines. J Plast Surg Hand Surg. 2014;48(1):67-73.
6. Reddy KK, Hanke CW, Tierney EP. Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature. J Drugs Dermatol. 2011;10(8):837-842.
7. Hong JY, Liu X, Mao M, et al. Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PLoS One. 2013;8(7):e69752.
8. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3(1):5.
9. Goldberg C, Hoang D, McRae M, Chung C, Leffell DJ, Narayan D. A strategy for the successful management of dermatofibrosarcoma protuberans. Ann Plast Surg. Published online ahead of print June 19, 2013.
10. Miller SJ, Alam M, Anderson JS, et al. Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw. 2012;10(3):312-318.
11. Khachemoune A, Barkoe D, Braun M, Davison SP. Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: multistaged repair with the use of skin expanders. Dermatol Surg. 2005;31(1):115-119.
12. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28.
A 55-year-old African American male presented with a 2-year history of a slow-growing, non-tender growth on his back. The lesion was treated as a hypertrophic scar with several injections of intralesional triamcinolone without improvement. The patient reported a rapid growth of the lesion in the 6 months prior to presentation. His past medical history was unremarkable. He has no past history of cutaneous malignancies or disorders of the skin.
On physical examination there was a firm red-brown fixed lesion with an irregular surface and asymmetrical borders measuring approximately 8.5 cm x 7.5 cm on the patient’s left upper back (Figure 1). The area was non-tender and there was no exudate or ulceration outside of the suture areas from previous biopsy.
What is Your Diagnosis?
Diagnosis:
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue tumor with a tendency to recur after excision. The estimated incidence is 4.2 to 4.5 cases per million each year in the United States, representing 0.1% of all malignancies.1-3 It commonly presents between age 30 and 50, although cases have been described in all age groups as well as congenital.3,4 The tumor demonstrates a racial predilection, with a greater incidence in African Americans than Caucasians.1
The etiology of DFSP is unknown. Reports have demonstrated that there is a relation to cutaneous trauma, including prior scars, burns, irradiated areas, as well as sites of tattoos.5,6 More than 90% of cases of DFSP have been associated with a specific chromosome translocation, t(17;22)(q22;q13). This translocation causes fusion of collagen, type 1 alpha 1 and platelet-derived growth factor-B (PDGFB), leading to increased production of growth factor and thus increased cellular proliferation.3,5,7
Clinical Presentations
DFSP often begins as an asymptomatic slow-growing nodule or plaque that is skin-colored or red to blue (Figure 1).
Figures 1. 8.5 cm x 7.5 cm nodule on the patient’s left upper back.
The tumor gradually enlarges and is locally destructive, often infiltrating surrounding fascia, muscle and bone.3,8 In advanced disease, the tumor may be characterized by ulceration, pain and bleeding. DFSP has the ability to metastasize hematogenously, although this is rare (1%-4%).8,9 Large tumor size and prolonged time for adequate diagnosis is common due to the tumor’s initial indolent appearance.10 DFSP most commonly occurs on the trunk (about 50%), followed by proximal extremities (25%-30%) and head and neck (10%-15%).3,8
DFSP has several variants. Bednar tumor is an uncommon pigmented variant in which the cells contain melanin.5 Giant cell fibroblastoma is considered a juvenile form of DFSP.4 Fibrosarcomatous DFSP is the transformation of DFSP to a more aggressive form with a greater potential for metastasis.5,8
Histopathology
Diagnosis is usually made by biopsy with examination of hematoxylin and eosin stained specimens under light microscopy.10 Histologically, DFSP can be identified by uniform proliferation of dermal spindle cells in a characteristic cartwheel or storiform pattern, with fingerlike projections into the deep dermis, underlying fat and other nearby tissues.3,5,11 The cells exhibit a low mitotic index and relatively low amounts of pleomorphism.3,8
DFSP can be further identified by immunohistochemistry in the event of an uncertain diagnosis, especially when differentiating it from a dermatofibroma. DFSP is positive for CD34 and stromolysin-3, but negative for Factor XIIIa.3,5,12 In contrast, dermatofibroma is usually negative for CD34 and positive for Factor XIIIa.3 The sensitivity of CD34 for DFSP is between 84% and 100%.3
Differential Diagnosis
Misdiagnosis and delay in diagnosis of DFSP is common. Small-sized DFSP may be difficult to clinically distinguish from a dermatofibroma, especially the cellular and deep variant.5 Other fibrous tumors, such as fibrosarcoma, atypical fibroxanthoma and nodular fasciitis should be considered.3 DFSP may also resemble a hypertrophic scar or keloid, or have a vascular appearance similar to a hemangioma.4,12 Other diagnostic considerations include neurofibroma, epidermal inclusion cysts, melanoma or metastatic cutaneous malignancy.4
Management
The National Comprehensive Cancer Network recommends diagnosis with biopsy, with re-biopsy if clinical suspicion is high following an initial negative biopsy.10
Once the diagnosis is confirmed, the initial treatment of DFSP is surgical. Achievement of adequate margins is critical due to high local recurrence secondary to the tumor’s infiltrative growth. Although not uniformally accepted by all authors, many recommend that Mohs micrographic surgery as the treatment of choice, with a recurrence rate around 1%.3,9 The recurrence rate following management with wide local excision (3 cm margins) is between 10% and 20%.11
Resection of DFSP often leads to large defects that may require reconstruction.11 Negative margins should be confirmed prior to reconstruction. Flaps provide superior cosmetic results compared to skin grafts, and tissue expansion may be needed for further esthetic considerations, especially for lesions on the face, head or neck.9,11
Molecular therapy with imatinib (Gleevec, Novartis), a PDGFB tyrosine kinase inhibitor, has been shown effective in treating DFSP with the t(17;22)(q22;q13) translocation. It is FDA approved to treat unresectable, recurrent or metastatic DFSP in adults.10 Drug resistance with imatinib has been described.7 Further, sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.), a B-Raf and vascular endothelial growth factor receptor inhibitor, has been reported to be efficacious in a case of DFSP that failed conventional therapy.8
DFSP is considered a radiosensitive tumor. Adjuvant radiotherapy is not necessary with clear surgical margins, but should be considered for unresectable or recurrent disease.10
Clinical follow-up is recommended due to a high rate of recurrence. An estimated 50% of recurrences occur within the first year post-excision, and 80% within 3 years.5,9
Our Patient
Pathologic evaluation of the biopsy specimen showed proliferation of spindle cells in a storiform pattern with downward projections into the deep dermis, consistent with dermatofibrosarcoma protuberans (Figure 2). The patient was educated on available treatment options including Mohs micrographic surgery and imatinib. The patient elected to undergo tumor removal using Mohs surgery. After negative margins were obtained, the repair of the defect was performed by plastic surgery. At 6 months follow-up, the patient demonstrated a well-healed surgical scar and no recurrence of local disease.
Figure 2. Proliferation of dermal spindle cells in a storiform pattern, with projections into the deep dermis.
Conclusion
Dermatofibrosarcoma protuberans is a rare, locally aggressive soft tissue tumor that often presents as an asymptomatic slow-growing nodule or plaque. Delay in diagnosis is common due to its initial benign appearance. Etiology is unknown but may be related to prior tissue trauma.
The mainstay of treatment is with surgical excision, preferentially Mohs micrographic surgery. Clear margins should be obtained, as local recurrence is common. Adjunct therapy with imatinib and/or radiation is recommended for recurrent or unresectable tumors.
Ms. Marchionne is a fourth-year medical student at the University of Nevada School of Medicine in Las Vegas, NV.
Dr. Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at the State University of New York Downstate in Brooklyn, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56(6):968-973.
2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S.: an analysis of 12,114 cases. Cancer. 2008;113(3):616-627.
3. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012;38(4):537-551.
4. Checketts SR, Hamilton TK, Baughman RD. Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature. J Am Acad Dermatol. 2000;42(5 Pt 2):907-913.
5. Akram J, Wooler G, Lock-Andersen J. Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines. J Plast Surg Hand Surg. 2014;48(1):67-73.
6. Reddy KK, Hanke CW, Tierney EP. Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature. J Drugs Dermatol. 2011;10(8):837-842.
7. Hong JY, Liu X, Mao M, et al. Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PLoS One. 2013;8(7):e69752.
8. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3(1):5.
9. Goldberg C, Hoang D, McRae M, Chung C, Leffell DJ, Narayan D. A strategy for the successful management of dermatofibrosarcoma protuberans. Ann Plast Surg. Published online ahead of print June 19, 2013.
10. Miller SJ, Alam M, Anderson JS, et al. Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw. 2012;10(3):312-318.
11. Khachemoune A, Barkoe D, Braun M, Davison SP. Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: multistaged repair with the use of skin expanders. Dermatol Surg. 2005;31(1):115-119.
12. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28.
Diagnosis:
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue tumor with a tendency to recur after excision. The estimated incidence is 4.2 to 4.5 cases per million each year in the United States, representing 0.1% of all malignancies.1-3 It commonly presents between age 30 and 50, although cases have been described in all age groups as well as congenital.3,4 The tumor demonstrates a racial predilection, with a greater incidence in African Americans than Caucasians.1
The etiology of DFSP is unknown. Reports have demonstrated that there is a relation to cutaneous trauma, including prior scars, burns, irradiated areas, as well as sites of tattoos.5,6 More than 90% of cases of DFSP have been associated with a specific chromosome translocation, t(17;22)(q22;q13). This translocation causes fusion of collagen, type 1 alpha 1 and platelet-derived growth factor-B (PDGFB), leading to increased production of growth factor and thus increased cellular proliferation.3,5,7
Clinical Presentations
DFSP often begins as an asymptomatic slow-growing nodule or plaque that is skin-colored or red to blue (Figure 1).
Figures 1. 8.5 cm x 7.5 cm nodule on the patient’s left upper back.
The tumor gradually enlarges and is locally destructive, often infiltrating surrounding fascia, muscle and bone.3,8 In advanced disease, the tumor may be characterized by ulceration, pain and bleeding. DFSP has the ability to metastasize hematogenously, although this is rare (1%-4%).8,9 Large tumor size and prolonged time for adequate diagnosis is common due to the tumor’s initial indolent appearance.10 DFSP most commonly occurs on the trunk (about 50%), followed by proximal extremities (25%-30%) and head and neck (10%-15%).3,8
DFSP has several variants. Bednar tumor is an uncommon pigmented variant in which the cells contain melanin.5 Giant cell fibroblastoma is considered a juvenile form of DFSP.4 Fibrosarcomatous DFSP is the transformation of DFSP to a more aggressive form with a greater potential for metastasis.5,8
Histopathology
Diagnosis is usually made by biopsy with examination of hematoxylin and eosin stained specimens under light microscopy.10 Histologically, DFSP can be identified by uniform proliferation of dermal spindle cells in a characteristic cartwheel or storiform pattern, with fingerlike projections into the deep dermis, underlying fat and other nearby tissues.3,5,11 The cells exhibit a low mitotic index and relatively low amounts of pleomorphism.3,8
DFSP can be further identified by immunohistochemistry in the event of an uncertain diagnosis, especially when differentiating it from a dermatofibroma. DFSP is positive for CD34 and stromolysin-3, but negative for Factor XIIIa.3,5,12 In contrast, dermatofibroma is usually negative for CD34 and positive for Factor XIIIa.3 The sensitivity of CD34 for DFSP is between 84% and 100%.3
Differential Diagnosis
Misdiagnosis and delay in diagnosis of DFSP is common. Small-sized DFSP may be difficult to clinically distinguish from a dermatofibroma, especially the cellular and deep variant.5 Other fibrous tumors, such as fibrosarcoma, atypical fibroxanthoma and nodular fasciitis should be considered.3 DFSP may also resemble a hypertrophic scar or keloid, or have a vascular appearance similar to a hemangioma.4,12 Other diagnostic considerations include neurofibroma, epidermal inclusion cysts, melanoma or metastatic cutaneous malignancy.4
Management
The National Comprehensive Cancer Network recommends diagnosis with biopsy, with re-biopsy if clinical suspicion is high following an initial negative biopsy.10
Once the diagnosis is confirmed, the initial treatment of DFSP is surgical. Achievement of adequate margins is critical due to high local recurrence secondary to the tumor’s infiltrative growth. Although not uniformally accepted by all authors, many recommend that Mohs micrographic surgery as the treatment of choice, with a recurrence rate around 1%.3,9 The recurrence rate following management with wide local excision (3 cm margins) is between 10% and 20%.11
Resection of DFSP often leads to large defects that may require reconstruction.11 Negative margins should be confirmed prior to reconstruction. Flaps provide superior cosmetic results compared to skin grafts, and tissue expansion may be needed for further esthetic considerations, especially for lesions on the face, head or neck.9,11
Molecular therapy with imatinib (Gleevec, Novartis), a PDGFB tyrosine kinase inhibitor, has been shown effective in treating DFSP with the t(17;22)(q22;q13) translocation. It is FDA approved to treat unresectable, recurrent or metastatic DFSP in adults.10 Drug resistance with imatinib has been described.7 Further, sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.), a B-Raf and vascular endothelial growth factor receptor inhibitor, has been reported to be efficacious in a case of DFSP that failed conventional therapy.8
DFSP is considered a radiosensitive tumor. Adjuvant radiotherapy is not necessary with clear surgical margins, but should be considered for unresectable or recurrent disease.10
Clinical follow-up is recommended due to a high rate of recurrence. An estimated 50% of recurrences occur within the first year post-excision, and 80% within 3 years.5,9
Our Patient
Pathologic evaluation of the biopsy specimen showed proliferation of spindle cells in a storiform pattern with downward projections into the deep dermis, consistent with dermatofibrosarcoma protuberans (Figure 2). The patient was educated on available treatment options including Mohs micrographic surgery and imatinib. The patient elected to undergo tumor removal using Mohs surgery. After negative margins were obtained, the repair of the defect was performed by plastic surgery. At 6 months follow-up, the patient demonstrated a well-healed surgical scar and no recurrence of local disease.
Figure 2. Proliferation of dermal spindle cells in a storiform pattern, with projections into the deep dermis.
Conclusion
Dermatofibrosarcoma protuberans is a rare, locally aggressive soft tissue tumor that often presents as an asymptomatic slow-growing nodule or plaque. Delay in diagnosis is common due to its initial benign appearance. Etiology is unknown but may be related to prior tissue trauma.
The mainstay of treatment is with surgical excision, preferentially Mohs micrographic surgery. Clear margins should be obtained, as local recurrence is common. Adjunct therapy with imatinib and/or radiation is recommended for recurrent or unresectable tumors.
Ms. Marchionne is a fourth-year medical student at the University of Nevada School of Medicine in Las Vegas, NV.
Dr. Khachemoune, the Section Editor of Derm DX, is with the department of dermatology at the State University of New York Downstate in Brooklyn, NY.
Disclosure: The authors report no relevant financial relationships.
References
1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56(6):968-973.
2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S.: an analysis of 12,114 cases. Cancer. 2008;113(3):616-627.
3. Bogucki B, Neuhaus I, Hurst EA. Dermatofibrosarcoma protuberans: a review of the literature. Dermatol Surg. 2012;38(4):537-551.
4. Checketts SR, Hamilton TK, Baughman RD. Congenital and childhood dermatofibrosarcoma protuberans: a case report and review of the literature. J Am Acad Dermatol. 2000;42(5 Pt 2):907-913.
5. Akram J, Wooler G, Lock-Andersen J. Dermatofibrosarcoma protuberans: clinical series, national Danish incidence data and suggested guidelines. J Plast Surg Hand Surg. 2014;48(1):67-73.
6. Reddy KK, Hanke CW, Tierney EP. Malignancy arising within cutaneous tattoos: case of dermatofibrosarcoma protuberans and review of literature. J Drugs Dermatol. 2011;10(8):837-842.
7. Hong JY, Liu X, Mao M, et al. Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing. PLoS One. 2013;8(7):e69752.
8. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3(1):5.
9. Goldberg C, Hoang D, McRae M, Chung C, Leffell DJ, Narayan D. A strategy for the successful management of dermatofibrosarcoma protuberans. Ann Plast Surg. Published online ahead of print June 19, 2013.
10. Miller SJ, Alam M, Anderson JS, et al. Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw. 2012;10(3):312-318.
11. Khachemoune A, Barkoe D, Braun M, Davison SP. Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the outer calvarial plate: multistaged repair with the use of skin expanders. Dermatol Surg. 2005;31(1):115-119.
12. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28.
