Dermatofibroma 

Updated: Jun 04, 2018
Author: Joseph C Pierson, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Dermatofibroma (superficial benign fibrous histiocytoma) is a common cutaneous nodule of unknown etiology that occurs more often in women. Dermatofibroma frequently develops on the extremities (mostly the lower legs) and is usually asymptomatic, although pruritus and tenderness can be present. It is actually the most common painful skin tumor.[1] A number of well-described, histologic subtypes of dermatofibroma have been reported. Removal of the tumor is usually not typically required unless diagnostic uncertainty exists or particularly troubling symptoms are present.

This article discusses primarily cutaneous (superficial) dermatofibroma. Subcutaneous (deep) benign fibrous histiocytomas are also well documented and may have a more aggressive clinical course, as can tumors displaying cellular, aneurysmal (hemosiderotic), and atypical histologic variants of dermatofibroma.

In addition, benign fibrous histiocytomas are reported in bone, orbital, airway, gastrointestinal, splenic, genitourinary, and intracranial locations.

Pathophysiology

The precise mechanism for the development of dermatofibroma is unknown. Rather than a reactive tissue change, evidence that dermatofibroma may be a neoplastic process is demonstrated by its clonal proliferative growth.[2] Clonality, by itself, is not necessarily synonymous with a neoplastic process; it has been demonstrated in inflammatory conditions, including atopic dermatitis, lichen sclerosis, and psoriasis. Dermatofibroma tumorigenesis may be due to distorted protein kinase C activity.[3]

Results from immunohistochemical testing with antibodies to factor XIIIa, which label dermal dendritic cells, are frequently positive in dermatofibroma, while antibodies to MAC 387, which label monocyte-derived macrophages (histiocytes), show less consistent results. One study evaluated the expression in dermatofibroma of HSP47, a recently used marker for skin fibroblasts; CD68, a marker for histiocytes; and factor XIIIa. Most of the spindle-shaped cells in all 28 cases of dermatofibroma, irrespective of histologic variant, stained positively with HSP47, indicating that skin fibroblasts are a major constituent of dermatofibroma. Factor XIIIa–positive dendritic cells also are present, but the presence of CD68-positive histiocytes was inconsistent, especially between histologic variants.[4] CD14+ monocytes have been proposed as the cell of origin of dermatofibromas.[5]

The cell surface proteoglycan, syndecan-1,[6] and fibroblast growth factor receptor 2, involved in epithelial-mesenchymal cross-talk,[7] may play a role in the growth of dermatofibromas. Transforming growth factor-beta (TGF-beta) signaling might be a trigger of the fibrosis seen in dermatofibromas.[8] TGF-beta, along with other fibrinogenic factors, may be produced by mast cells, which have been reported to occur in abnormally high numbers in dermatofibromas.[9]

Gene fusions have been described in dermatofibroma tumorigenesis.[10, 11] ALK gene rearrangement and overexpression has been demonstrated in the epithelioid and atypical dermatofibroma variants.[12, 13]

Etiology

Historically attributed to be a reactive process to some traumatic insult to the skin (eg, arthropod bite, skin tattooing, tuberculin skin testing, prior folliculitis),[14, 15, 16, 17] the cause of dermatofibroma is unknown. Clonal analysis suggest it may represent a true neoplasm.[2]

Altered immunity likely plays a role in many cases of multiple eruptive dermatofibromas associated with various underlying conditions and medications (see History).

A study of eruptive dermatofibromas in a kindred suggests that a genetic component may exist.[18]

Epidemiology

Frequency

Dermatofibromas are relatively common.

Race

Frequency of dermatofibroma appears to be similar in all races.

Sex

Females are affected by dermatofibroma more commonly than males, with a male-to-female ratio of 1:2, or higher.[19, 20]

Age

Dermatofibroma can occur in patients of any age. In one series, 80% of biopsy specimens were from patients aged 20-49 years,[19] and in another the mean age of the patients was 42.18±13.72 years.[20]

Prognosis

Typical superficial dermatofibromas are considered benign lesions, and the prognosis for patients with this condition is excellent. However, discomfort from pain or itching may be significant.

Deep, cellular, aneurysmal (hemosiderotic), and atypical variants, which are notoriously more locally recurrent (≤20% of cases), can rarely metastasize.[21, 22, 23] (The deep subset of dermatofibroma that arises in the subcutaneous or deep soft tissue may undergo further classification.[22] ) Such variants, or any indeterminant dermatofibroma, might be regarded as potentially malignant lesions.[24] In these exceptional cases, pulmonary and nodal metastases were most commonly seen, some patients developed multiple satellite nodules, and deaths have occurred.[25] The primary tumors tended to be large and cellular, but aggressive behavior is not entirely predictable, although early or frequent recurrences of the tumor should raise concern.[25] Array-based comparative genomic hybridization (CGH) may prove useful in identifying these higher-risk variants.[26, 27, 22]

The epithelioid variant has also been reported to metastasize, although demonstration of ALK gene rearrangement may indicate it is a biologically distinct tumor.[12]

In a study of common dermatofibromas with an increased mitotic rate but no other worrisome features, none recurred or metastasized.[28]

Spontaneous regression has been reported,[29] and this may yield postinflammatory hypopigmentation, although this appears to be quite rare.

Patient Education

For patient education resources, see the Procedures Center, as well as Mole Removal.

 

Presentation

History

Dermatofibromas typically arise slowly and most often occur as a solitary nodule on an extremity, particularly the lower leg, but any cutaneous site is possible. Dermatofibromas are usually asymptomatic, but itching and pain often are noted. They are the most common of all painful skin tumors.[1] Women who shave their legs may be bothered by the razor traumatizing the lesion in that region, causing pain, bleeding, erosive changes, and ulceration. Although cases of unusually rapid growth exist, most dermatofibromas remain static for decades or persist indefinitely. Patients may describe a hard mole or unusual scar and are often concerned about the possibility of skin cancer.

Several lesions may be present, but rarely are numerous (ie, ≥15) tumors found. This multiple eruptive variant occurs in less than 1% of patients, approximately 60% of whom have an underlying systemic condition, such as HIV infection or systemic lupus erythematosus.[30, 31, 32] However, dermatomyositis,[33] Graves disease,[34] Hashimoto thyroiditis,[35] myasthenia gravis,[35] Down syndrome,[36] leukemia,[37] myelodysplastic syndrome,[38] cutaneous T-cell lymphoma,[39] multiple myeloma,[39] atopic dermatitis,[40] Crohn disease,[41] and ulcerative colitis[42] have all been reported in association with the phenomenon. In addition, antiretroviral agents,[43] the biologic agent efalizumab,[44] antitumor necrosis factor-alpha agents,[45] and the tyrosine kinase inhibitor imatinib[46] have been linked to their appearance.

Both congenital[47] and acquired[48] cases of multiple clustered dermatofibromas have been reported.

Physical Examination

Typically, the clinical appearance of dermatofibroma is a solitary, 0.5- to 1-cm nodule. A sizable minority of patients may have several lesions, but rarely (< 1% of cases) are more than 15 lesions present. (See History) The overlying skin can range from flesh to gray, yellow, orange, pink, red, purple, blue, brown, or black, or a combination of hues (see the image below). On palpation, the hard nodule may feel like a small pebble fixed to the skin surface and is freely movable over the subcutis. Tenderness may be elicited with manipulation of the lesion.

Erythematous, slightly hyperpigmented nodule on th Erythematous, slightly hyperpigmented nodule on the leg. Courtesy of David Barnette, MD.

The characteristic tethering of the overlying epidermis to the underlying lesion with lateral compression (pinching), called the dimple sign, may be a useful clinical sign for diagnosis.[49] However, presence of the dimple sign does not always assure the lesion is dermatofibroma,[50] and dermatoscopy may be useful in supporting the clinical impression.[51]

The extremities are the most common sites of involvement, particularly the legs.[19, 20] Although any cutaneous site can be seen, palm, sole, digital, oral, and genital involvement is relatively rare. Giant (>5 cm in diameter),[52] atrophic,[53] polypoid,[54] and dermatofibroma with spreading satellitosis[55] variants have been reported. The largest reported tumor was 17 x 9 x 4 cm.[56]

Multiple clustered dermatofibromas[48] are rare and can mimic dermatofibrosarcoma protuberans. This phenomenon has been reported in a segmental distribution.[57]

A halo of dermatitis (Meyerson phenomenon) surrounding a dermatofibroma occurred in one patient.[58]

 

DDx

 

Workup

Imaging Studies

A study of localized lesions of the skin imaged via variable-frequency ultrasound included the image of a hypoechoic solid nodule created by a dermatofibroma.[59] Dermatofibromas have been analyzed by high-definition optical coherent tomography.[60]

Dermatofibroma can mimic a malignant lesion on fluorodeoxyglucose positron-emission tomography (FDG-PET) scans.[61]

Procedures

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.[62] Dermoscopy of a xanthomatous dermatofibroma shows a homogeneous pattern with shades of yellow and a peripheral pigment network.[63] A green color may indicate the hemosiderotic variant.[64] If a suggestive melanocytic or atypical pattern is noted with dermoscopy, a diagnostic biopsy is warranted.[65]

Confocal laser scanning microscopy findings have been described.[66]

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.[67] 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.[68]

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).[69]  

Antibodies toward factor XIIIa and CD34 are useful in distinguishing the two tumors, with the former suggesting dermatofibroma and the latter suggesting DFSP.[70] However, occasional CD34 positivity occurs in the cellular variant of dermatofibroma.[71, 72] 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.[73]

Stromelysin-3 (ST-3) expression of dermatofibroma by immunohistochemical staining may also be useful in differentiation from DFSP.[74]

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.[75]

Immunostaining with insulinlike growth factor–binding protein 7 (IGFBP7) is positive more frequently in dermatofibroma and aids in the differentiation from DFSP.[76]

Nestin, expressed in only 13% of dermatofibroma, but 94% of DFSP, could be a useful marker to distinguish between these two tumors.[77]

Collagen triple helix repeat containing-1 (Cthrc1) staining is positive much more frequently in DFSP and is another potential discriminating test.[78]

D2-40 immunostain appears to be a sensitive marker for dermatofibromas, including the cellular variant, can aid in differentiation from DFSP.[79]

Cathepsin K expression[80] and immunohistochemical analysis of chemokine receptor CXCR4[81] are other possible tools in delineating the two tumors.

Indeterminate tumors that share histologic and immunohistochemical features of dermatofibroma and DFSP have been described[82] ; however, those studied do not harbor the COL1A1-PDGFB chimeric transcripts of DFSP.[83]

Expression of FGFR3/FOXN1 and FGF2/FGFR4 in dermatofibroma pathogenesis may also help differentiate from DFSP.[84]

CD99 has been used alone or in combination with factor XIIIa and CD34 to differentiate dermatofibroma from DFSP.[85, 86, 87]

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.[88]

Fluorescence in situ hybridization (FISH) analysis may be helpful in differentiating dermatofibroma from DFSP.[89]

B-cell lymphoma 2 (Bcl-2) expression may help distinguish subcutaneous dermatofibroma from DFSP.[90]

One clinicopathologic classification scheme[91] describes the following four categories of dermatofibroma:

  • Those with architectural peculiarities, such as deep penetrating, atrophic, giant, aneurysmal (angiomatoid), 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,[92] 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, 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[93] 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[94] 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.

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.[95]

Immunoperoxidase staining is consistently positive for both CD10 and actin in dermatofibromas.[96] 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.[97]

Lichenoid dermatofibroma,[98] ulcerated dermatofibroma,[98] erosive dermatofibroma,[98] dermatofibroma with diffuse eosinophilic infiltrate,[99] dermatofibroma accompanied by perforating dermatosis,[100] and one showing perforating dermatosis with floret-type multinucleated giant cells have been described.[101] Dermatofibromas with overlying sebaceous hyperplasia,[102] with intracytoplasmic eosinophilic globules,[103] signet-ring cells,[104] amyloid light chain deposition,[105] and incidental acantholysis[106] have also been reported. A case of an apocrine gland cyst with a hemosiderotic dermatofibroma was termed an apocrine hemosiderotic dermatofibroma.[107] Cutaneous adenodermatofibroma (entrapped apocrine structures without hemosiderotic changes), keloidal, collapsing angiokeloidal, and dermatofibromas with dystrophic calcification variants have been reported.[108, 109, 110, 111] Blue nevus associated with dermatofibroma has been reported, as has coexisting leukemia cutis.[112, 113]

One case of mycosis fungoides showed histologic features of dermatofibroma.[114]

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.[96] Dermatofibromas of the shoulder have a high incidence of sebaceous induction with seborrheic keratosis‒like hyperplasia.[115]

A case series[116] 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.[117] A case report[118] documenting an invasive melanoma occurring in association with a dermatofibroma underscores the role of these immunohistochemical stains.

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 2 lesions.[119]

 

Treatment

Approach Considerations

No treatment is usually necessary for dermatofibromas. Simple reassurance that the lesion is benign may be indicated, unless one of the aggressive subtypes is suspected or diagnosed.

Intralesional steroid injections have been attempted with variable results.

Surgical Care

For cosmetically unacceptable lesions, those that are particularly symptomatic, if there is any diagnostic uncertainty, or when one of the aggressive subtypes is suspected, complete excision, including the subcutaneous fat, is the ideal procedure. Obtaining a 3-mm margin has been shown to completely remove typical dermatofibromas.[120] One of the aggressive histologic subtypes, aneurysmal dermatofibroma, has been successfully treated via Mohs micrographic surgery.[121]

An inverted pyramidal biopsy technique may allow for an aesthetically pleasing result, while still providing adequate tissue for histologic findings.[122]

Superficially shaving the lesion or cryosurgery can be attempted for cosmesis or to decrease the symptoms; however, recurrences are more likely.

Carbon dioxide and pulsed-dye laser treatments have been used in the treatment of dermatofibromas.[123, 124]

Long-Term Monitoring

If the dermatofibroma is not removed and significant change occurs in the color, size, border, or symptoms, the patient should seek follow-up evaluation.

If complete removal has been previously attempted, patients with lesions that recur should seek follow-up evaluation. An aggressive subtype or another diagnosis should be ruled out.

If multiple eruptive lesions develop, screening for a family history of such and for underlying associated diseases and medications is warranted (See History).

 

Questions & Answers