Introduction
Background
Dermatofibroma (DF) is a common cutaneous nodule of unknown etiology that occurs more often in women. The lesion frequently develops on the extremities (mostly the lower legs) and is usually asymptomatic, although pruritus and tenderness are not uncommon. The latter feature is seen in a sufficient number of patients to make dermatofibroma the most prevalent of all painful skin tumors. A number of well-described, histologic subtypes have been reported. Removal of the tumor is not necessary unless diagnostic uncertainty exists or particularly troubling symptoms are present.
Pathophysiology
The precise mechanism for the development of dermatofibroma is unknown. Rather than a reactive tissue change, dermatofibroma seems more likely to be a neoplastic process because of the persistent nature of the lesion and the demonstration that it is a clonal proliferative growth.1 Clonality, of course, by itself, is not necessarily synonymous with a neoplastic process; it has been demonstrated in inflammatory conditions, including atopic dermatitis, lichen sclerosis, and psoriasis.
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.2
The cell surface proteoglycan, syndecan-1,3 and fibroblast growth factor receptor 2, involved in epithelial-mesenchymal cross-talk,4 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.5 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.6
Frequency
United States
Dermatofibromas are relatively common.
International
Incidence of dermatofibroma is probably similar to that in the United States.
Mortality/Morbidity
Dermatofibroma is regarded as a benign lesion; however, discomfort from pain or itching may be significant. The few case reports of metastatic dermatofibroma are disputable from the standpoint of histologic diagnosis. Such reported lesions were highly cellular, of large size, and locally recurrent.7 Some do regard the cellular dermatofibroma subtype as a malignant lesion.8 Indolent pulmonary metastases also were observed.
One report describes a patient with a 9-cm subcutaneous deep fibrous histiocytoma who developed metastases and died. Deep fibrous histiocytoma has been regarded as a subset of dermatofibroma that arises in the subcutaneous or deep soft tissue, but the classification of the deep variant may evolve.9
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 1:4.
Age
Dermatofibroma can occur in patients of any age, but it usually develops in young adulthood. Approximately 20% of the lesions occur before age 17 years.
Clinical
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. Several lesions may be present, but only rarely are multiple (ie, 15 or more) tumors found. This multiple variant is seen most frequently in the setting of autoimmune disease or altered immunity, such as systemic lupus erythematosus, Graves disease,10 HIV infection, or leukemia and may be indicative of worsening immunoreactivity. Mild regression has been reported with clinical improvement of the underlying disorder. Conversely, drugs used to treat the underlying disorders have also been implicated in causation. Multiple eruptive dermatofibromas developed in a patient with psoriasis who was receiving efalizumab.11 Multiple clustered dermatofibromas have also been reported.12 Patients may describe a hard mole or unusual scar and may be concerned about the possibility of skin cancer.
Dermatofibromas are characteristically asymptomatic, but itching and pain often are noted. They are the most common of all painful skin tumors.13 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. Uncommon reports describe spontaneous regression,14 and this may yield postinflammatory hypopigmentation. A case of asteatotic eczema developing around a dermatofibroma on an edematous lower extremity has been described.15
Physical
Typically, the clinical appearance is a solitary, 0.5- to 1-cm nodule. A sizable minority of patients may have several lesions, but rarely are more than 15 lesions present. The overlying skin can range from flesh to gray, yellow, orange, pink, red, purple, blue, brown, or black, or a combination of hues (see Media File 1). On palpation, the hard nodule may feel like a frozen pea or 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 the leg. Courtesy of David Barnette, MD.
The characteristic tethering of the overlying epidermis to the underlying lesion with lateral compression, called the dimple sign, may be a useful clinical sign for diagnosis.16 The dimple sign is not unique to dermatofibroma, and dermatoscopy may be useful in supporting the clinical impression.17
The extremities are the most common sites of involvement, particularly the lower legs. Although any cutaneous site can be seen, palm and sole involvement is rare. Giant (>5 cm in diameter), atrophic, atypical polypoid and dermatofibroma with satellitosis variants have been reported.
Causes
Historically attributed to some traumatic insult to the skin (eg, arthropod bite), the cause of dermatofibroma is unknown. Because of its persistent nature, dermatofibroma is probably better categorized as a neoplastic process rather than a reactive tissue change. A study of eruptive dermatofibromas in a kindred suggests that a genetic component may exist.18
More on Dermatofibroma |
 Overview: Dermatofibroma |
| Differential Diagnoses & Workup: Dermatofibroma |
| Treatment & Medication: Dermatofibroma |
| Follow-up: Dermatofibroma |
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| References |
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References
Chen TC, Kuo T, Chan HL. Dermatofibroma is a clonal proliferative disease. J Cutan Pathol. Jan 2000;27(1):36-9. [Medline].
Kuroda K, Tajima S. Proliferation of HSP47-positive skin fibroblasts in dermatofibroma. J Cutan Pathol. Jan 2008;35(1):21-6. [Medline].
Sellheyer K, Smoller BR. Dermatofibroma: upregulation of syndecan-1 expression in mesenchymal tissue. Am J Dermatopathol. Oct 2003;25(5):392-8. [Medline].
Skroza N, Rotolo S, Ceccarelli S, et al. Modulation of the expression of the FGFR2-IIIb and FGFR2-IIIc molecules in dermatofibroma. J Dermatol Sci. Jul 2008;51(1):53-7. [Medline].
Kubo M, Ihn H, Yamane K, Tamaki K. The expression levels and the differential expression of transforming growth factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans. Br J Dermatol. May 2006;154(5):919-25. [Medline].
Yamamoto T. Dermatofibroma: a possible model of local fibrosis with epithelial/mesenchymal cell interaction. J Eur Acad Dermatol Venereol. Apr 2009;23(4):371-5. [Medline].
Colome-Grimmer MI, Evans HL. Metastasizing cellular dermatofibroma. A report of two cases. Am J Surg Pathol. Nov 1996;20(11):1361-7. [Medline].
Kimyai-Asadi A, Goldberg LH, Greenberg C, et al. Cellular, atypical, and indeterminate dermatofibromas: benign or malignant?. Dermatol Surg. Sep 2008;34(9):1264-71; discussion 1271-2. [Medline].
Gleason BC, Fletcher CD. Deep "benign" fibrous histiocytoma: clinicopathologic analysis of 69 cases of a rare tumor indicating occasional metastatic potential. Am J Surg Pathol. Mar 2008;32(3):354-62. [Medline].
Lopez N, Fernandez A, Bosch RJ, Herrera E. Multiple eruptive dermatofibromas in a patient with Graves-Basedow disease. J Eur Acad Dermatol Venereol. Mar 2008;22(3):402-3. [Medline].
Santos-Juanes J, Coto-Segura P, Mallo S, Galache C, Soto J. Multiple eruptive dermatofibromas in a patient receiving efalizumab. Dermatology. 2008;216(4):363. [Medline].
De Unamuno P, Carames Y, Fernandez-Lopez E, Hernandez-Martin A, Pena C. Congenital multiple clustered dermatofibroma. Br J Dermatol. May 2000;142(5):1040-3. [Medline].
Naversen DN, Trask DM, Watson FH, Burket JM. Painful tumors of the skin: "LEND AN EGG". J Am Acad Dermatol. Feb 1993;28(2 Pt 2):298-300. [Medline].
Niemi KM. The benign fibrohistiocytic tumours of the skin. Acta Derm Venereol Suppl (Stockh). 1970;50(63):Suppl 63:1-66. [Medline].
Cox NH. Halo asteatotic eczema localized around a dermatofibroma in acute-onset leg oedema. Br J Dermatol. Aug 2008;159(2):496. [Medline].
Fitzpatrick TB, Gilchrest BA. Dimple sign to differentiate benign from malignant pigmented cutaneous lesions. N Engl J Med. Jun 30 1977;296(26):1518. [Medline].
Meffert JJ, Peake MF, Wilde JL. 'Dimpling' is not unique to dermatofibromas. Dermatology. 1997;195(4):384-6. [Medline].
Samlaska C, Bennion S. Eruptive dermatofibromas in a kindred. Cutis. Mar 2002;69(3):187-8, 190. [Medline].
Zaballos P, Puig S, Llambrich A, Malvehy J. Dermoscopy of dermatofibromas: a prospective morphological study of 412 cases. Arch Dermatol. Jan 2008;144(1):75-83. [Medline].
Cavicchini S, Tourlaki A, Tanzi C, Alessi E. Dermoscopy of solitary yellow lesions in adults. Arch Dermatol. Oct 2008;144(10):1412. [Medline].
Demir MK, Ozdemir H, Gençhallaç H, Altaner S, Kartal O. Dermatofibroma mimicking malignancy on integrated F-18 fluorodeoxyglucose PET-CT. Diagn Interv Radiol. Mar 2009;15(1):61-3. [Medline].
Kideryova L, Lacina L, Dvorankova B, et al. Phenotypic characterization of human keratinocytes in coculture reveals differential effects of fibroblasts from benign fibrous histiocytoma (dermatofibroma) as compared to cells from its malignant form and to normal fibroblasts. J Dermatol Sci. Jul 2009;55(1):18-26. [Medline].
Nair V, Weinreb I, MacNeil N, Szollosi Z, Chetty R, Ghazarian D. A unique biphasic variant of cutaneous fibrous histiocytoma with a storiform pattern and intralesional pigmented melanocytes: "storiform melano-fibrous histiocytoma". Eur J Dermatol. May-Jun 2008;18(3):332-6. [Medline].
Goldblum JR, Tuthill RJ. CD34 and factor-XIIIa immunoreactivity in dermatofibrosarcoma protuberans and dermatofibroma. Am J Dermatopathol. Apr 1997;19(2):147-53. [Medline].
Kim HJ, Lee JY, Kim SH, et al. Stromelysin-3 expression in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans: comparison with factor XIIIa and CD34. Br J Dermatol. Aug 2007;157(2):319-24. [Medline].
Horenstein MG, Prieto VG, Nuckols JD, Burchette JL, Shea CR. Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans?. Am J Surg Pathol. Jul 2000;24(7):996-1003. [Medline].
Mori T, Misago N, Yamamoto O, Toda S, Narisawa Y. Expression of nestin in dermatofibrosarcoma protuberans in comparison to dermatofibroma. J Dermatol. Jul 2008;35(7):419-25. [Medline].
Zelger BG, Zelger B. [Dermatofibroma. A clinico-pathologic classification scheme]. Pathologe. Nov 1998;19(6):412-9. [Medline].
Gonzalez-Vela MC, Val-Bernal JF, Martino M, Gonzalez-Lopez MA, Garcia-Alberdi E, Hermana S. Sclerotic fibroma-like dermatofibroma: an uncommon distinctive variant of dermatofibroma. Histol Histopathol. Jul 2005;20(3):801-6. [Medline].
de Feraudy S, Mar N, McCalmont TH. Evaluation of CD10 and procollagen 1 expression in atypical fibroxanthoma and dermatofibroma. Am J Surg Pathol. Aug 2008;32(8):1111-22. [Medline].
Spaun E, Zelger B. Dermatofibroma with intracytoplasmic eosinophilic globules: an unusual phenomenon. J Cutan Pathol. Jul 2009;36(7):796-8. [Medline].
Garrido-Ruiz MC, Carrillo R, Enguita AB, Peralto JL. Signet-ring cell dermatofibroma. Am J Dermatopathol. Feb 2009;31(1):84-7. [Medline].
Gonzalez S. Regarding the case report of Dr Phillip W. Allen on apocrine gland cyst with hemosiderotic dermatofibroma. Adv Anat Pathol. Nov 2008;15(6):376; author reply 376. [Medline].
King R, Googe PB, Page RN, Mihm MC Jr. Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ. Mod Pathol. Aug 2005;18(8):1043-7. [Medline].
Kovach BT, Boyd AS. Melanoma associated with a dermatofibroma. J Cutan Pathol. May 2007;34(5):420-2. [Medline].
Orrock JM, Abbott JJ, Gibson LE, Folpe AL. INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneoplastic mimics. Am J Dermatopathol. Apr 2009;31(2):152-6. [Medline].
Weber PJ, Moody BR, Foster JA. Inverted pyramidal biopsy. Dermatol Surg. Jul 2001;27(7):681-4. [Medline].
Krupa Shankar DS, Kushalappa AA, Suma KS, Pai SA. Multiple dermatofibromas on face treated with carbon dioxide laser. Indian J Dermatol Venereol Leprol. May-Jun 2007;73(3):194-5. [Medline].
Fernandez-Flores A, Manjon JA. Mitosis in dermatofibroma: a worrisome histopathologic sign that does not necessarily equal recurrence. J Cutan Pathol. Sep 2008;35(9):839-42. [Medline].
Aiba S, Terui T, Tagami H. Dermatofibroma with diffuse eosinophilic infiltrate. Am J Dermatopathol. Jun 2000;22(3):281-4. [Medline].
Alexandrescu DT, Wiernik PH. Multiple eruptive dermatofibromas occurring in a patient with chronic myelogenous leukemia. Arch Dermatol. Mar 2005;141(3):397-8. [Medline].
Aydin E, Vardareli OS, Bilezikci B, Ozgirgin ON. [Dermatofibroma accompanied by perforating dermatosis in the auricle: a case report]. Kulak Burun Bogaz Ihtis Derg. 2005;15(3-4):83-6. [Medline].
Curcó N, Jucgla A, Bordas X, Moreno A. Dermatofibroma with spreading satellitosis. J Am Acad Dermatol. Dec 1992;27(6 Pt 1):1017-9. [Medline].
Evans J, Clarke T, Mattacks CA, Pond CM. Dermatofibromas and arthropod bites: is there any evidence to link the two?. Lancet. Jul 1 1989;2(8653):36-7. [Medline].
Fuciarelli K, Cohen PR. Sebaceous hyperplasia: a clue to the diagnosis of dermatofibroma. J Am Acad Dermatol. Jan 2001;44(1):94-5. [Medline].
Heenan PJ. Tumors of the fibrous tissue involving the skin. In: Elder D, ed. Lever's Histopathology of the Skin. 8th ed. Philadelphia, Pa: Lippincott-Raven; 1997:847-53.
Hong SB, Yang MH, Lee MH, Haw CR. Dermatofibroma-like atypical granular cell tumour. Acta Derm Venereol. 2005;85(2):179-80. [Medline].
Lookingbill DP. A malignant dimple. N Engl J Med. Oct 13 1977;297(15):841-2. [Medline].
Requena L, Farina MC, Fuente C, et al. Giant dermatofibroma. A little-known clinical variant of dermatofibroma. J Am Acad Dermatol. May 1994;30(5 Pt 1):714-8. [Medline].
Sanchez RL. The elusive dermatofibromas. Arch Dermatol. Apr 1990;126(4):522-3. [Medline].
Shinojima Y, Hara H, Shimojima H, Terui T. Cutaneous chondroma with overlying pigmentation clinically mimicking dermatofibroma. Br J Dermatol. Jan 2006;154(1):178-81. [Medline].
Sánchez Yus E, Soria L, de Eusebio E, Requena L. Lichenoid, erosive and ulcerated dermatofibromas. Three additional clinico-pathologic variants. J Cutan Pathol. Mar 2000;27(3):112-7. [Medline].
Troxel DB. An insurer's perspective on error and loss in pathology. Arch Pathol Lab Med. Oct 2005;129(10):1234-6. [Medline].
Wick MR, Ritter JH, Lind AC, Swanson PE. The pathological distinction between "deep penetrating" dermatofibroma and dermatofibrosarcoma protuberans. Semin Cutan Med Surg. Mar 1999;18(1):91-8. [Medline].
Zelger B, Zelger BG, Burgdorf WH. Dermatofibroma-a critical evaluation. Int J Surg Pathol. Oct 2004;12(4):333-44. [Medline].
Zelger BG, Sidoroff A, Zelger B. Combined dermatofibroma: co-existence of two or more variant patterns in a single lesion. Histopathology. Jun 2000;36(6):529-39. [Medline].
Further Reading
Keywords
dermatofibroma, benign fibrous histiocytoma, dermal dendrocytoma, dermatofibroma lenticulare, fibroma durum, fibroma simplex, histiocytoma, histiocytoma cutis, nodular subepidermal fibrosis, sclerosing angioma, sclerosing hemangioma
