Dermatofibroma Workup

Updated: Aug 07, 2020
  • Author: Joseph C Pierson, MD; Chief Editor: Dirk M Elston, MD  more...
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Imaging Studies

A study of localized lesions of the skin imaged via variable-frequency ultrasonography included the image of a hypoechoic solid nodule created by a dermatofibroma. [65] Dermatofibromas have been analyzed by high-definition optical coherent tomography. [66]

Dermatofibroma can mimic a malignant lesion on fluorodeoxyglucose positron-emission tomography (FDG-PET) scans. [67]



For those trained in dermoscopy, this may be a useful adjunctive diagnostic technique for dermatofibromas. The most common pattern seen is a peripheral pigment network with a central white area. [68] Dermoscopy of a xanthomatous dermatofibroma shows a homogeneous pattern with shades of yellow and a peripheral pigment network. [69] A green color may indicate the hemosiderotic variant. [70] If a suggestive melanocytic or atypical pattern is noted with dermoscopy, a diagnostic biopsy is warranted. [71]

Confocal laser scanning microscopy findings have been described. [72]

If any diagnostic uncertainty exists, excisional biopsy into the subcutaneous fat is advised.


Histologic Findings

The overlying epidermis is usually acanthotic. Pseudoepitheliomatous hyperplasia and a basaloid proliferation may be noted. The hyperplasia may be caused by the action of fibroblasts on epidermal keratinocytes. [73] Increased pigment may be seen, which may be iron or melanin. Most lesions display a grenz zone of normal papillary dermis overlying the tumor.

The bulk of the tumor is within the mid dermis where no capsule is present and the periphery of the lesion blends with the surrounding tissue. Whorling fascicles of a spindle cell proliferation with excessive collagen deposition are characteristic. At the periphery, the spindle cells characteristically wrap around normal collagen bundles (see the images below). Occasionally, melanocytes have been reported to be interspersed amongst the spindle cells. [74]

Acanthotic epithelium with basilar hyperpigmentati Acanthotic epithelium with basilar hyperpigmentation (dirty feet) over a dermal spindle cell proliferation (X10). Courtesy of David Barnette, MD.
Collagen trapping by the dermal fibrohistiocytic i Collagen trapping by the dermal fibrohistiocytic infiltrate (X40). Courtesy of David Barnette, MD.

The subcutis typically is preserved, but if involved (especially when a storiform [cartwheel] pattern is observed), be alert to the possibility of the lesion being a dermatofibrosarcoma protuberans (DFSP), [75] which can be a challenge and merits further discussion.

Antibodies toward factor XIIIa and CD34 are useful in distinguishing the two tumors, with the former suggesting dermatofibroma and the latter suggesting DFSP. [76] However, occasional CD34 positivity occurs in the cellular variant of dermatofibroma. [77, 78] Dermatofibromas retain elastic fibers, while these are fragmented or displaced in DFSP. This can be assessed with fluorescence microscopy of hematoxylin and eosin (H&E) sections or with an elastic stain. [79]

Stromelysin-3 (ST-3) expression of dermatofibroma by immunohistochemical staining may also be useful in differentiation from DFSP. [80]

Transforming growth factor-beta type I and type II receptor expression patterns may also help distinguish between dermatofibroma and DFSP. [8] Thrombospondin-1 (TSP-1) mediates TGF-beta I activation, and its elevated expression in DFSP may aid in the differential diagnosis. [81]

Immunostaining with insulinlike growth factor–binding protein 7 (IGFBP7) is positive more frequently in dermatofibroma and aids in the differentiation from DFSP. [82]

Nestin, expressed in only 13% of dermatofibroma, but 94% of DFSP, could be a useful marker to distinguish between these two tumors. [83]

Collagen triple helix repeat containing-1 (Cthrc1) staining is positive much more frequently in DFSP and is another potential discriminating test. [84]

D2-40 immunostain appears to be a sensitive marker for dermatofibromas, including the cellular variant, can aid in differentiation from DFSP. [85]

Cathepsin K expression [86] and immunohistochemical analysis of chemokine receptor CXCR4 [87] are other possible tools in delineating the two tumors.

Indeterminate tumors that share histologic and immunohistochemical features of dermatofibroma and DFSP have been described [88] ; however, those studied do not harbor the COL1A1-PDGFB chimeric transcripts of DFSP. [89]

Expression of FGFR3/FOXN1 and FGF2/FGFR4 in dermatofibroma pathogenesis may also help differentiate from DFSP. [90]

CD99 has been used alone or in combination with factor XIIIa and CD34 to differentiate dermatofibroma from DFSP. [91, 92, 93]

Leukocyte-specific protein 1 (LSP1) may aid in differentiation of dermatofibroma from DFSP. [5]

5-Hydroxymethylcytosine (5-hmC) may be a useful marker to distinguish dermatofibroma from DFSP. [94]

Fluorescence in situ hybridization (FISH) analysis may be helpful in differentiating dermatofibroma from DFSP. [95]

B-cell lymphoma 2 (Bcl-2) expression may help distinguish subcutaneous dermatofibroma from DFSP. [96]

Autophagy marker Atg5 could be a differential marker to differentiate dermatofibroma from DFSP. [97]

Phosphohistone-H3 and Ki67 are useful markers for differentiating dermatofibroma from DFSP. [98]

A histologic review of 192 dermatofibromas found 80% common type, 5.7% aneurysmal, 5.7% hemosiderotic, 2.6% epithelioid, 2.1% cellular, 2.1% lipidized, 1% atrophic, and 0.5% clear cell. [99]

One clinicopathologic classification scheme [100] describes the following four categories of dermatofibroma:

  • Those with architectural peculiarities, such as deep penetrating, atrophic, giant, aneurysmal, hemangiopericytomalike, palisading, or ossifying variants

  • Cellular/stromal dermatofibromas, such as clear cell, granular cell, myofibroblastic, sclerotic, monster cell, atypical (pseudosarcomatous), hemosiderotic, cholesterotic (lipidized), and myxoid variants: While the cholesterotic variant has been described in association with metabolic syndrome, [101] it is more likely that cholesterol results from breakdown of cell membranes within the lesion rather than as a result of circulating lipids.

  • Dermatofibromas with architectural and cellular/stromal changes in homogeneous arrangement, including epithelioid cell (epithelioid fibrous histiocytoma may be a biologically distinct tumor [12, 29] ), cellular benign, smooth-muscle proliferative, basal cell carcinoma–like, pseudolymphomatous, multinucleate cell angiohistiocytoma (perhaps not a subtype of dermatofibroma), cellular neurothekeoma, plexiform fibrohistiocytic tumor, plexiform xanthoma, and plexiform xanthomatous tumor subtypes

  • A complex, composite, or combined dermatofibroma [102] category with 2 or more architectural and cellular/stromal patterns in a single lesion

Of the variants listed above, keep in mind that the uncommon sclerotic fibromalike dermatofibroma should be differentiated from sclerotic fibroma. One study [103] showed 7 of 7 of the former lesions to be negative for CD34 and CD99, while 3 of 3 solitary fibromas were positive for CD34 and CD99. For comparison, 14 of 14 "common-type" dermatofibromas in this study were negative for CD34, while 4 demonstrated positivity with CD99.

Immunoperoxidase staining is consistently positive for both CD10 and actin in dermatofibromas. [104] CD10 was positive in 11 of 11 dermatofibromas and only positive in 1 of 7 epithelioid dermatofibromas, so it was postulated that epithelioid dermatofibroma may be a distinct entity. [105]

INI-1, present in 100% of dermatofibromas, but decreased or absent in the vast majority of epithelioid sarcomas in one study, can help distinguish between the two lesions. [106]

Lichenoid dermatofibroma, [107] ulcerated dermatofibroma, [107] erosive dermatofibroma, [107] dermatofibroma with diffuse eosinophilic infiltrate, [108] dermatofibroma accompanied by perforating dermatosis, [109] and one showing perforating dermatosis with floret-type multinucleated giant cells have been described. [110] Dermatofibromas with overlying sebaceous hyperplasia, [111] with intracytoplasmic eosinophilic globules, [112] signet-ring cells, [113] amyloid light chain deposition, [114] and incidental acantholysis [115] have also been reported. A case of an apocrine gland cyst with a hemosiderotic dermatofibroma was termed an apocrine hemosiderotic dermatofibroma. [116] Cutaneous adenodermatofibroma (entrapped apocrine structures without hemosiderotic changes), keloidal, collapsing angiokeloidal, and dermatofibromas with dystrophic calcification variants have been reported. [117, 118, 119, 120]  Blue nevus associated with dermatofibroma has been reported, as has coexisting leukemia cutis and Langerhans cell histiocytosis. [121, 122, 123]

One case of mycosis fungoides showed histologic features of dermatofibroma. [124]

Induction of hyperplasia in nearby structures by dermatofibroma is frequently described. In a study of over 10,000 dermatofibromas, associated induction (where follicular germinative and sebaceous glandular induction were seen in 6% of cases), cellular alterations, and stromal alterations are outlined with their attributes. [104] Dermatofibromas of the shoulder have a high incidence of sebaceous induction with seborrheic keratosis‒like hyperplasia. [125]

A case series [126] reported the uncommon occurrence of dermatofibroma and melanocytic lesions in the same biopsy specimen. Four of 14 specimens showed the 2 processes to seemingly merge imperceptibly. The lesions included junctional, dermal, and compound nevi, as well as a single case of melanoma in situ. Knowledge of this relationship can help prevent rendering the wrong diagnosis and is facilitated by the use of immunohistochemistry, with the melanocytic lesions showing S-100 and Mart-1 positivity with FXIIIa negativity and the dermatofibroma showing S-100 and Mart-1 negativity and FXIIIa positivity. Another tool is Sox10 immunoreactivity, which is positive in melanocytic lesions, but not fibrohistiocytic proliferations. [127] A case report [128] documenting an invasive melanoma occurring in association with a dermatofibroma underscores the role of these immunohistochemical stains.

The presence of perineural invasion may suggest malignant behavior in a dermatofibroma. [129]

Scanning electron microscopy findings of histologically confirmed dermatofibroma lesions have been described. [130]