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California Tumor Tissue Registry’s
Case of the Month
CTTR COTM www.cttr.org Vol 9:8
May, 2007
A 24 year old woman presented with recurrent masses involving right ankle. Previous
tumors had been excised five times with the last excision being two years previously.
Multiple masses in the right ankle were up to 3.0 cm in greatest diameter and were
located distal and inferior to the right lateral malleolus (Fig. 1). Sections revealed a
highly cellular spindle cell lesion that was superficial, immediately underlying the skin
(Fig. 2). Some areas showed incorporation of benign adipocytes (Fig. 3, left) but most of
the tumor lacked fat (Fig. 3, right). The tumor displayed a profound storiform growth
pattern (Fig. 4). Neither bizarre nuclear pleomorphism nor lengthy fascicles suggestive
of fibrosarcomatous change were encountered. Despite the hypercellularity, mitotic
figures were only rarely found. Immunostains were positive for CD34 and negative for
S100. EMA showed non-specific staining (Fig. 5). CD99 was negative.
Diagnosis: “Dermatofibrosarcoma Protuberans (DFSP)”
Michelle A. Fajardo, DO, MT(ASCP), and Donald R. Chase, MD
Department of Pathology, Loma Linda University and Medical Center
California Tumor Tissue Registry
Dermatofibrosarcoma protuberans (DFSP) is a low grade mesenchymal tumor first
described in 1924 by Darier and Ferrand. It is locally aggressive and usually involves the
superficial tissues of the trunk or extremities. Rarely it occurs in the head and neck
region. It initially presents as a plaque-like lesion which slowly evolves into multiple
nodules which push up the skin giving it a “protuberant” appearance (Fig. 1). The
nodules tend to merge forming yet larger nodules.
DFSP has several variants. The plaque form shows slender, large spindle cells growing
parallel to the skin surface. Mitotic figures are rare. The nodular form demonstrates
uniform, slender, spindle cells with the characteristic storiform or cartwheel pattern. A
fibrosarcomatous form tends to lack the storiform pattern and evolves into a
characteristic herringbone pattern and shows increased cellular atypia and mitotic figures.
Other variants include the pigmented Bednar tumor which incorporates melanin. Rarely,
DFSP is diffusely myxoid and consists of a uniform population of spindled cells without
CTTR’s Case of the Month
May, 2007
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the usual storiform growth pattern. Irrespective of the variant, however, DFSP stains
positively for CD34.
The differential diagnosis of DFSP includes fibrohistiocytic lesions such as:




Benign fibrous histiocytoma
Malignant fibrous histiocytoma
Neurofibroma
Myxoid liposarcoma
Benign fibrous histiocytoma is a solitary, small symmetrical lesion with stellate
fibroblasts which abut subcutaneous fat but fail to infiltrate it. It fails to stain for
CD34, and in contrast to DSFP demonstrates significant staining with Factor XIII.
Malignant fibrous histiocytoma (MFH) is characterized by marked bizarre
pleomorphism that is lacking in a DFSP. It is also distinguished by its numerous
atypical mitoses, hemorrhage, and necrosis. MFH usually occurs in deep soft tissue
and rarely involves the subcutis.
Neurofibromas are characterized by irregular spindle-shaped cells associated with
thin strands of wavy collagen sometimes separated by a mucinous matrix. Unlike
DFSP, the tumor is positive for S100 protein.
Myxoid forms of DFSP may resemble myxoid liposarcoma but are much more
cellular and lack the presence of a delicate plexiform vascular pattern and microcysts.
DFSP is always superficial and liposarcoma usually involves deeper tissue.
DFSP is a locally aggressive tumor with a high rate of local recurrence (~50%). It has
only limited potential for metastasis. After multiple resections, however, the metastatic
possibility increases mandating that this low grade sarcoma be adequately excised at the
time of the initial diagnosis. Its high rate of local recurrence reflects its subtle infiltrative
border beyond the margins that can be physically palpated. Wide local excision is the
traditional initial treatment of choice with radiation later given as adjunctive therapy for
incompletely excised tumors or patients with unresectable disease. Mohs micrographic
surgery is also a possible first-line treatment.
Metastases are rare and are usually preceded by recurrent disease. DFSP may distantly
spread via either lymphatic or hematogenous routes and usually migrates to regional
lymph nodes or lung(s). There is controversy as to whether fibrosarcomatous
transformation of the tumor is directly related to increased metastatic potential. Some
studies have described no difference in the behavior of the transformed and conventional
forms while others have suggested an increased risk of metastasis when the tumor has
dedifferentiated into fibrosarcoma.
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May, 2007
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The development of molecular targeted therapy shows promise as a treatment option for
patients with unresectable or metastatic disease. Molecular studies have shown DFSP to
have a chromosomal translocation involving the COL1A1 gene on chromosome 17 and
the platelet-derived growth factor B-chain gene (PDGF-B) on chromosome 22. These
findings have led to recent studies which have demonstrated successful treatment with
imantinib mesylate (Gleevec), a tyrosine kinase inhibitor, which blocks the activity of the
PDGF receptor.
Suggested Reading:
Abbott JJ, Oliviera Am, Nascimento AG. The prognostic significance of
fibrosarcomatous transformation in dermatofibrosarcoma protuberans. Am J Surg Pathol
30(4):436-443, 2006.
Dagan R, Zlotecki RA, Scarborough MT, Mendenhall WM. Radiotherapy in the
treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 28(6); 537-539, 2005.
Kondapalli L, Soltani K, Lacouture ME. The promise of molecular targeted therapies:
protein kinase inhibitors in the treatment of cutaneous malignancies. J Am Acad
Dermatol 53(2):291-302, 2005.
Labropoulos SV, Fletcher JA, Oliviera AM, Papadopoulos S, Razis ED. Sustained
complete remission of metastatic dermatofibroma protuberans with imatinib mesylate.
Anticancer Drugs 16(4):461-466, 2005.
McArthur GA. Dermatofibrosarcoma protuberans: A surgical disease with a molecular
savior. Current Opin Onco 18 (4): 341-346, 2006.
Pennington BE, Leffell DJ. Mohs micrographic surgery: Established uses and emerging
trends. Oncol 19(9):1165-1175, 2005.
Ruiz-Tovar J, Fernandez Guarino M, Reguero Callejas ME, Aguilera Velardo A, Arano
Bermejo J, Cabanas Navarro L. Dermatofibrosarcoma protuberans: Review of 20 years
experience. Clin Translat Oncol 8:606-610, 2006.
Saiki H, Tmada Y, Watanabe D, Akita Y, Matsumoto Y, Imai C, Kadono T, Maekawa T,
Hattori N, Watanabe A, Torii H, Tamaki K. Analysis of gene mutations in four cases of
dermatofibrosarcoma protuberans. Clin Exper Dermatol 31(3):441-444, 2006.
Szollosi Z, Nemes Z. Transformed dermatofibrosarcoma protuberans: A
clinicopathological study of eight cases. J Clin Pathol 58(7):751-756, 2005.
Weiss SW, Enzinger FM. Soft Tissue Tumors, 4th Ed. Mosby Inc.: St. Louis, MO,
2001.
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