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Skin - Nonmelanocytic tumors

Other tumors of skin

Dermatofibrosarcoma protuberans (DFSP)

Reviewer: Christopher Hale, M.D. (see Reviewers page)
Revised: 14 September 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Part of WHO classification for skin tumors, not soft tissue tumors
● Low to intermediate grade malignancy, usually of dermis, with prominent storiform pattern of monomorphic fibroblast-like cells that invade into subcutis (Dermatofibrosarcoma Protuberans, eMedicine)
● Also called intermediate (borderline) fibrous histiocytoma
● Slow growing, low-grade malignant neoplasm of trunk and various sites but not hands and feet
● Rare, usually adults 20-40 years, more common in blacks in US (J Am Acad Dermatol 2007;56:968)
● Can occur in infants (Arch Dermatol 2007;143:203) and children (J Plast Reconstr Aesthet Surg 2009;62:819)
● May be a peculiar type of nerve sheath tumor since CD34 positive, or may derive from a subset of CD34 positive dermal dendritic cells
● Locally aggressive, low rate of metastasis (only after repeated failures at local control)
● May progress to fibrosarcoma or MFH
● Giant cell fibroblastoma is considered the juvenile variant of DFSP as it has the same translocation (Am J Surg Pathol 2003;27:27)

Bednar’s tumor:
● 5-10% of cases
● Pigmented variant due to dendritic cells with melanin, S100+ only in pigmented cells, HMB45 negative
● Associated with black patients

Case reports
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● Atrophic variant (J Dermatol 2006;33:486)
● Granular cell variant (Am J Surg Pathol 2002;26:932)
● Myoid differentiation in fibrosarcomatous DFSP (Acta Dermatovenerol Alp Panonica Adriat 2006;15:39)
● Sclerosing variant (Int J Dermatol 2006;45:59)

Treatment
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● Imatinib therapy (tyrosine kinase inhibitor) is gold standard for treatment of inoperable or recurrent DFSP (Sarcoma 2011;2011:959132)
● Must excise subcutaneous fat (wide local excision with 2-3 cm margins) to prevent recurrence (Plast Reconstr Surg 2007;119:1779)
● Three dimensional histologic evaluation of margins recommended (Ann Surg Oncol 2004;11:438)
● Imatinib may be effective in CD117 negative tumors (J Clin Oncol 2005;23:866)

Clinical images
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Papulonodular thigh lesions


Before and after Imatinib treatment

Gross description
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● Nodular, polypoid or plaque-like, centered in dermis, can occur in deep soft tissue
● Mean 5 cm, gray-white (brown/black if melanocytes present), may appear circumscribed
● Hemorrhage and necrosis are rare

Micro description
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● Non circumscribed, highly cellular, “tight” storiform pattern (cells radiating in spokes at right angles around a central point that often contains a vessel) that infiltrates deeply into subcutaneous tissue and entraps fat cells to form characteristic honeycomb pattern
● Some tumors show areas of fascicular growth
● Storiform pattern may be absent in early plaque stage
● Cells are monomorphic, thin and spindly with scant eosinophilic cytoplasm and hyperchromatic nuclei resembling neurofibroma
● May have numerous mitotic figures, but not atypical ones
● Collagen usually non-polarizable and thin
● Only mild pleomorphism and focal atypia
● May coexist with giant cell fibroblastoma
● Usually no significant pleomorphism, no/rare histiocytes, no histiocyte-like cells, no foam cells, no giant cells or other inflammatory cells

Variants:
● Atrophic (depressed lesion), collagenous (with central thick collagen bundles), granular cell (S100 negative), myxoid (see below), palisading, pigmented, sclerosing

Micro images
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Small uniform cells radiating like pinwheels from central area that often has a blood vessel is characteristic


Uniform cells with no significant pleomorphism, minimal intercellular collagen,
no/rare foam cells or giant cells, which are characteristic of benign fibrous histiocytoma


Fine strands of collagen are present

       
Infiltration of fat causes tumor cells to surround fat cells


Residual fat cells are in linear arrangement resembling a string of pearls,
which is characteristic of DFSP but not benign fibrous histiocytoma


DFSP with diminished storiform pattern but CD34+ (not shown)


Pigmented cells are not common


Variants: with fibrosarcomatous component, myxoid, pigmented

Cytology
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● Homogeneous with isolated spindle cells, often tissue fragments with storiform pattern, fibrillary stromal fragments, naked nuclei
● Occasional slight to moderate atypia (Diagn Cytopathol 2004;30:261)

Positive stains
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● CD34 (strong in 95%), vimentin
● Also actin (focal), ApoD (Am J Surg Pathol 2004;28:1063)
● bcl2, NKI-C3 (Am J Clin Pathol 1992;97:478)
● CD99 (J Cutan Pathol 2008;35:647)

Negative stains
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● Factor XIIIa (usually), keratin, EMA, S100, HMB45, desmin, CD117 (J Cutan Pathol 2007;34:857)

Electron microscopy description
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● Stellate or spindle cells with long, slender, ramified cell processes joined by primitive junctions, often with subplasmalemmal densities
● Commonly multivesicular buds (Ultrastruct Pathol 2006;30:283)

Molecular/cytogenetics
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● t(17,22)(q21;q13) [collagen type 1 alpha 1 gene and platelet derived growth factor beta chain gene, OMIM #607907] found in almost all cases using multiplex RT-PCR (Hum Path 2008;39:184)
● Also supernumerary ring chromosomes derived from t(17;22) (Oncogene 2001;20:2965)
● Rarely other translocations (Virchows Arch 2008;452:689)

Differential diagnosis
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● Dermatofibroma: also storiform but non-infiltrative, less cellular than DFSP, Factor XIIIa positive, CD34 negative
● Thymoma: storiform but different location, CD34 negative
● MFH-pleomorphic or atypical fibroxanthoma: storiform pattern but also moderate/marked pleomorphism and nuclear atypia

Indeterminate lesions between DFSP and dermatofibroma

General
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● Report of 10 tumors with features of both tumors, all Factor XIIIa+, CD34+, although in different cells (Am J Surg Pathol 2000;24:996)
● Clinically, one recurrence at mean 22 months follow-up
● Recommend complete excision
● Cytogenetics may help distinguish

Myxoid variant of DFSP

General
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● DFSP with 50%+ myxoid stroma
● Uncommon
● Median age 40 years, male and female
● Extremities, head and neck, trunk, anogenital region
● Associated with recurrent tumor
● Similar prognosis as classic DFSP (Am J Surg Pathol 2007;31:1371)
● Should distinguish from post-traumatic CD34+ myxoid dermatofibrohistiocytoma (J Cutan Pathol 2009;36:84)

Case reports
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● 54 year old woman with supraclavicular mass (Case of the Week #132)

Treatment
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● Complete excision
● Occasional recurrences (Am J Dermatopathol 2007;29:443)

Gross description
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● Median 3 cm, white-tan-gray-yellow, firm to gelatinous

Micro description
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● Infiltrative, often hypocellular, sheet-like, bland spindle cells with pale eosinophilic cytoplasm, spindled nuclei, no pleomorphism
● Stroma is myxoid with prominent thin walled vessels
● Diffuse infiltration of fat
● Also cellular areas typical of DFSP

Micro images
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Case of the week

Virtual slides
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Myxoid DFSP

Positive stains
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● CD34

Negative stains
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● S100, muscle markers, CD99

Differential diagnosis
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● Myxoid neurofibroma: wavy nuclei, often intratumoral axons, strong S100+
● Superficial angiomyxoma: myxoid stroma with numerous small vessels, may be CD34+, but does not infiltrate fat, tends to be less cellular
● Myxoid liposarcoma: vessels are more abundant, delicate and branching, lipoblasts are prominent

Sarcomas arising in DFSP

General
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● Usually resembles fibrosarcoma, rarely MFH-pleomorphic
● Good prognosis (Clin Sarcoma Res 2012;2:4); in cases with wide local excision and negative margins, 20% recur, metastatic rate varies from 0% (Am J Surg Pathol 2000;24:1125), to 10% (Am J Surg Pathol 2006;30:436)
● Report as “DFSP with areas of fibrosarcoma”, indicate extent of fibrosarcomatous change, nuclear grade, level of mitotic activity

Case reports
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● 28 year old woman with rapidly growing facial lesion (Head Neck Oncol 2011 Feb 4;3:5)
● 42 year old woman with abdominal mass (Arch Pathol Lab Med 2006;130:882)

Treatment
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● Wide local excision

Micro description
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● In fibrosarcomatous areas, spindle cells intersect at acute angles, chromatin is coarser than usual, increased mitotic activity

Micro images
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Fibrosarcoma arising in DFSP:
       
DFSP cells trap fat cells, fibrosarcoma cells are more uniform

   
Fibrosarcoma cells are spindled, uniform and hyperchromatic and arranged in herringbone pattern


Uncommon finding is myoid nodules containing cells with eosinophilic cytoplasm, present in DFSP
or fibrosarcomatous areas, cells are actin+, CD34-, desmin-


H&E and FISH


Mitotic activity

Pleomorphic sarcoma arising in DFSP:

Tumor cells are pleomorphic and have granular chromatin

End of Skin - Nonmelanocytic tumors > Other tumors of skin > Dermatofibrosarcoma protuberans (DFSP)

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