Dermatofibrosarcoma_0913 Derm Look 1
Keloid_0913 Derm Look 2
A man, aged 41 years, presented with a painful growing “lump” on his right upper back that he first noted 10 months earlier. At first, the lump was skin-colored and firm, but it had recently become darker in color and had developed surface irregularities. Review of symptoms was otherwise negative. Medical and surgical history was unremarkable. On physical examination, a firm erythematous plaque with irregular nodules was appreciated on the right upper back. Several indurated erythematous papules were also noted in the surrounding the area.
A 42-year-old woman presented with a slowly enlarging pruritic lesion on her chest. She stated that the lesion started two years ago as a firm scar that developed after an elective excision of an epidermal inclusion cyst. However, the lesion had continued to enlarge and was growing outside the confines of the original wound. Physical examination revealed a large and slightly erythematous firm plaque on the mid-chest. Claw-like extensions were noted on the peripheral borders of the plaque, while centrally, the plaque was skin-colored and softer.
TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Erythema and scaling of the finger and nail bed and Yellow plaques in bilateral inguinal creases.
Submit your diagnosis to see full explanation.
Case #1: Dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans (DFSP) is an uncommon and locally aggressive intermediate malignancy with a high recurrence rate. In the United States, DFSP accounts for approximately 1% of all soft tissue sarcomas.
Although DFSP may be seen in all ages, those most affected are young to middle-aged adults; males may have a slight predominance over females. DFSP is seen equally in all races, but an uncommon pigmented variant of DFSP (Bednar tumor) has been reported to occur much more frequently in blacks.
The exact pathogenesis and cellular origin of DFSP remains unknown. Some have suggested that pluripotent progenitor cells may be the origin of DFSP. These pluripotent cells have the capacity of differentiating into fibroblastic, histiocytic, and neuroectodermal cells, and all three of these cell lines are thought be a component of DFSP.1
Recent studies have also found such cytogenetic abnormalities as reciprocal translocations (t17;22) and supernumerary ring chromosomes containing sequences from chromosomes 17 and 22.1,2 These rearrangements fuse together the collagen type I alpha 1 (COL1A1) and the platelet-derived growth factor beta-chain (PDGFB) gene.
This puts the PDGFB gene under control of the COL1A1 promoter, which drives fusion protein production. The fusion protein is later processed into functional PDGFB, which subsequently interacts with the PDGF receptor on the surface of DFSP tumor cells and triggers tumor-cell proliferation.
It is estimated that approximately 90% of DFSP tumors harbor this translocation. Initially, DFSP presents as a slow-growing, asymptomatic, firm, skin-colored plaque. As the lesion enlarges, it may become painful and develop violaceous to red-brown nodules that measure one to several centimeters in diameter. The lesions are indurated and firm due to their attachment to the subcutaneous tissues.
DFSP favors the trunk in 50% to 60% of patients, with a predilection for the shoulder and pelvic areas. The tumors may also be seen on the proximal extremities in 20% to 30% of patients; head and neck lesions account for 10% to 15% of cases. Depending on the clinical subtype, DFSP may be clinically confused with a large dermatofibroma, dermatomyofibroma, morphea, keloid, leiomyoma, metastatic tumors, and malignant melanoma.
Early lesions of plaque DFSP are poorly circumscribed with a diffuse infiltration of slender, spindle-shaped cells arranged in fascicles that run parallel to the skin surface. Often, the adnexal structures are obliterated and the spindle cells infiltrate into the subcutaneous tissue, forming a multilayered pattern.
Nodular-stage tumors become more cellular, and the spindle cells form short fascicles, which are arranged into what is known as a cartwheel or storiform pattern. A cartwheel pattern is one in which the spindle cells have elongated nuclei that radiate from a center point. A storiform pattern describes spindle cells that are arranged in a matted, irregularly whorled pattern that resembles a straw mat. At the base of the lesion, neoplastic cells infiltrate the subcutaneous tissue in a honeycomb pattern.
Cytologically, the cells may have a deceptively bland appearance, with rare mitotic activity and minimal cellular atypia. Bednar tumors are an uncommon variant of DFSP that contains melanin-producing cells with schwannian differentiation. Other histologic variants include atrophic, myxoid, and fibrosarcomatous.
The histologic differential diagnosis for DFSP is broad and includes dermatofibroma, dermatomyofibroma, fibrosarcoma, neurofibroma, malignant peripheral nerve sheath tumor, leiomyoma, leiomyosarcoma, spindle-cell squamous cell carcinoma, desmoplastic melanoma, and atypical fibroxanthoma.
Immunostaining of DFSP demonstrates that the spindle cells are strongly positive for the anti-CD-34 antibody and are negative for factor XIIIa. This feature distinguishes DFSP from large dermatofibromas, which are CD34-negative and factor XIIIa-positive.
Presence of the S100 protein may help to differentiate neural tumors and desmoplastic melanoma from DFSP. Spindle-cell squamous cell carcinomas are pankeratin-positive, and smooth-muscle tumors are smooth-muscle actin- and desmin-positive.
Atypical fibroxanthomas are usually seen on sun-exposed skin in older patients, have a high degree of cellular atypia, and may show positivity with multiple stains including CD68, CD10, smooth-muscle actin, and pro-collagen I. DFSP and keloids are histologically distinct.
The treatment of choice for DFSP is complete surgical excision. Because of the tendency for DFSP to invade locally and recur frequently, Mohs micrographic surgery is often advocated because of its tissue-sparing advantage and lower recurrence rates.3
In general, DFSP carries a low risk of metastasis; however, the fibrosarcomatous variant of DFSP tends to have a higher rate of local recurrence and risk for distant metastasis. When distant metastases are present, the lung is the most commonly involved site. In locally advanced or metastatic disease, imatinib mesylate (Gleevec), which targets the PDGF receptor, may serve as a beneficial adjuvant treatment. A recent study showed a complete response to this medication in 50% of patients with locally advanced disease.4
In this case, a biopsy of the man’s lesion revealed the diagnosis of DFSP. Treatment with Mohs micrographic surgery resulted in histologic clearance of the tumor. The patient continues to be followed in the dermatology clinic with no evidence of recurrent disease to date.
Case #2: Keloid
Beyond the second trimester of fetal development, only the epidermis has the potential to fully regenerate. Therefore, wounds that extend into the dermis will always heal with a scar.
Hypertrophic scarring occurs when the wound heals with far more than what is considered to be normal scar tissue. When the exuberant scar tissue extends beyond the boundaries of the original wound, it is referred to as a keloid. Keloid comes for the Greek word chele, or crab claw.
The incidence of keloids is highly variable and ranges from 0.09% in predominantly white populations to as high as 16% in darkly pigmented populations.5 Keloids can occur at any age but are rarely seen in children and the elderly.
Slight gender differences have been reported, with women outnumbering men; however, these differences are likely skewed by the fact that ear-piercing is more commonly seen in females, and women may more readily seek medical consultation for cosmetic improvement.
Despite the fact that keloids have been described for centuries, little is known about the exact pathogenesis. Familial tendency and prior skin trauma are the most consistently seen risk factors, but keloid formation without prior trauma can occur. Infection, acne, excessive wound tension, and the presence of foreign material can lead to increased inflammation, which is also thought to be associated with keloid formation.
It has been hypothesized that melanin-producing melanocytes may play a role in the pathogenesis since keloids are seen more frequently in darkly pigmented individuals and have never been reported to occur in those with oculocutaneous albinism.
Others have proposed that mast-cell mediators, which are known to upregulate collagen synthesis, may be the culprit because increased numbers of mast cells are often observed in keloids. Transforming growth factor-β (TGF-β) is another likely instigator as this protein is expressed at higher concentrations in keloidal fibroblasts than in normal control fibroblasts. In addition, a recent study revealed that athymic mice formed keloid-like nodules after injection of genetically modified human fibroblasts that overexpressed TGF-β.6
Keloids are pink, erythematous, or hyperpigmented fibrous plaques that occur most frequently in the sternal region. Other commonly affected areas include the neck, ears, extremities, and/or trunk. The face, genitals, palms, and soles are rarely affected. The overlying epidermis is often smooth and shiny, while the dermis is firm to palpation.
Keloids are often multiple and may occur as pinpoint papules or large plaques. Hypertrophic scars remain in the area of original injury and tend to resolve with time. Keloids extend beyond the area of original injury and may have claw-like projections at the borders, with regression in the central portion of the lesion. Patients may complain of pain, pruritus, or both.
Histologically, hypertrophic scars contain nodular and whorled masses of excess collagen admixed with fibroblastic cells. Keloids are less cellular and contain a dense nodular growth of myofibroblasts and thickened eosinophilic collagen bundles. The dermal nodule may cause thinning of the papillary dermis and atrophy of adjacent appendages. Elastic tissue is decreased, just as in a normal scar. Mucopolysaccharides are often increased, and mast cells may be present. Hypertrophic scars have vertically oriented vessels, whereas keloids have reduced vascularity.
Differentiating keloids from hypertrophic scars can be difficult. As mentioned earlier, keloids extend beyond the original injury, while hypertrophic scars are limited to the area of injury. Dermatofibromas are small, firm papules that are most commonly observed on the extremities and often have a characteristic tethering of the overlying epidermis to the underlying lesion with lateral compression (i.e., the dimple sign).
DFSP also commonly presents as a firm plaque on the trunk. However, there is usually no history of trauma, and irregular nodules may be present within the firm plaque. With time, DFSP may also become attached to deeper structures and ulcerate.
Other entities in the differential diagnosis include sarcoidosis, the sclerotic form of xanthoma disseminatum, lobomycosis, and the keloidal forms of scleroderma and morphea.
Keloids are frequently recalcitrant to therapy, so treatment can be challenging. Because of this, many treatment modalities have been employed, most of which feature off-label uses of prescription medication. The best treatment is prevention. Elective procedures should be avoided in people who are prone to developing keloids. Wound closure should be performed with minimal tension, and adjunctive therapies should be considered before abnormal wound healing has occurred.
Intralesional corticosteroids are the most commonly used therapy; repeated injections are typically performed every four to eight weeks with most doses ranging from 10 mg/mL to 40 mg/mL. Ideally, such treatment will lead to flattening of the lesion and improvement of any associated pain and/or pruritus.
Risk factors associated with intralesional corticosteroids include surrounding hypopigmentation and atrophy caused by lymphatic spread of the corticosteroid. Topical corticosteroids have been used as well, but the results are less reliable. Surgical excision alone leads to recurrence of keloids in approximately 80% of cases.
However, many clinicians combine surgery (to debulk the lesion) with such other treatment modalities as postoperative intralesional triamcinolone acetonide (Kenalog), intralesional interferon-α-2b (Intron A), x-ray irradiation, pressure, topical mitomycin C (Mitosol, Mutamycin), and topical imiquimod (Aldara, Zyclara).7
Other treatment options include silicone gel sheets, laser (flashlamp-pumped pulsed dye), 5-fluorouracil, intralesional bleomycin, cryotherapy, topical tacrolimus (Protopic), topical retinoids, and intralesional verapamil (Cala, Covera, Isoptin, Verelan).7
The patient in this case was treated with monthly intralesional acetonide 20 mg/mL until the lesion flattened and the pruritus subsided.
Kerri Robbins, MD, is an instructor in the Department of Dermatology at Baylor College of Medicine in Houston.
- Dimitropoulos VA. Dermatofibrosarcoma protuberans. Dermatol Ther. 2008;21:428-432.
- Pedeutour F, Simon MP, Minoletti F, et al. Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement. Cytogenet Cell Genet. 1996;72:171-174.
- Hollmig ST, Sachdev R, Cockerell CJ, et al. Spindle cell neoplasms encountered in dermatologic surgery: a review. Dermatol Surg. 2012;38:825-850.
- McArthur GA, Demetri GD, van Oosterom A, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol. 2005;23:866-873. Available at jco.ascopubs.org/content/23/4/866.long.
- Bloom D. Heredity of keloids; review of the literature and report of a family with multiple keloids in five generations. N Y State J Med. 1956;56:511-519.
- Campaner AB, Ferreira LM, Gragnani A, et al. Upregulation of TGF-b1 expression may be necessary but is not sufficient for excessive scarring. J Invest Dermatol. 2006;126:1168-76. Available at www.nature.com/jid/journal/v126/n5/full/5700200a.html.
- Love PB, Kundu RV. Keloids: an update on medical and surgical treatments. J Drugs Dermatol. 2013;12:403-409. Available at jddonline.com/articles/dermatology/S1545961613P0403X.