Dermatofibrosarcoma Protuberans: Retrospective Single Center Analysis Over 16 Years.

Dermatofibrosarcoma protuberans (DFSP) is rare mesenchymal neoplasia with a high risk of local recurrence but a low risk of metastatic spread. Tumor cells express CD34 and show a characteristic translocation t(17;22)(q22;q13). We analysed the documented cases at the Department of Dermatology and Allergology between 08/2001 and 08/2017. The diagnosis had been confirmed by histology and immunohistology in all cases. We identified four adults and a pediatric patient with DFSP. All patients were treated by wide surgical excision and controlled by three-dimensional histologic margin control. We observed no recurrence and no metastatic spread. We discuss prognostic factors and emerging treatments.

Introduction

Dermatofibrosarcoma protuberans (DFSP) is rare mesenchymal neoplasia of skin and soft tissue. Most cases develop on trunk and extremities as nodules or plaques, sometimes hyperpigmented. The hyperpigmented type is also known as Bednar a tumour. There is a wide age range, although incidence shows a peak between the second and fifth decade of life.

Diagnosis is made by histology, immunohistology and cytogenetic analysis [1].

DFSP is characterised by a relatively high risk of local recurrence but low risk of metastatic spread. In most cases, a chromosomal translocation can be found: t(17;22)(q22;q13). Thereby, the genes COL1A1 and platelet-derived growth factor (PDGF)-beta fuse. This leads to an autocrine stimulation loop involving PDGF-beta and PDGF-beta receptor [2].

We analysed our files for DFSP-patients, treatment, and outcome and discussed emerging treatments.

Material and Methods

We analysed the files of the Department of Dermatology and Allergology, Academic Teaching Hospital Dresden during a 16-year period, i.e. 08/2001 to 08/2017. Demographics, tumour characteristics, treatment and outcome, were investigated.

Results

We were able to identify five patients with a histologically confirmed diagnosis of DFSP. Maximal tumour diameter was between 2 and 4 cm. All tumours were staged T1(≤ 5 cm of tumour diameter on trunk and extremities), N0, M0, G1 (low grade). All tumours were ordinary DFSP without fibrosarcomatous transformation. One tumour was hyperpigmented (Bednar type).

The youngest patient was a 10-year-old girl with a rapidly growing, painless nodule of the chest (Fig. 1). A diagnostic skin biopsy was taken, that revealed large uniform spindle cells reactive with CD34 but negative for S100. Several mitoses were noted. The proliferative fraction as measured by Ki67-reactivity was 1%. A tumour was removed by wide surgical excision with 2 cm safety margin and complete removal of soft tissue down to the muscle fascia by slow Mohs technique. 3-dimensional histologic margin control was performed. The resulting defect was closed by tissue advancement flap after wide subcutaneous mobilisation of wound margins. Healing was uneventful. The 5-year follow-up was relapse-free.

Figure 1

Juvenile dermatofibrosarcoma protuberans on the chest of a 10-year-old girl. (a) Clinical presentation of a well-circumscribed plaque; (b) Defect after wide excision

The remaining patients were adults aged 24, 27, 43, and 61 years of age. The sex ratio for the adult patients was 1:1. One female patient was referred with a recurrence after first surgery elsewhere. The localisation was a shoulder, hip, epigastrium and under belly (Fig. 2).

Figure 2

Nodular dermatofibrosarcoma protuberans on the underbelly of a 61-year-old male patient. (a) Clinical presentation; (b) Safety margins; (c) Defect after wide excision; (d) Defect closure by tissue advancement

The safety margins were 1 – 4 cm according to German guidelines [3][4]. In all patients, tumour-free margins were documented. In 4 of five tumours, only one surgical session was necessary, in a single tumour two sessions were needed to obtain tumour-free margins.

Tumor cells were positive for CD34 but negative for S100, desmin, pan-cytokeratin, epithelial membrane antigen, and actin. The proliferative index was 1% to 10% measured by Ki67 reactivity. Tumor staging excluded metastatic spread.

Defect closure could be realised by tissue advancement flaps; no grafts were needed. During follow up of up to 7 years neither recurrence nor metastasis was noted.

Discussion

DFSP is rare mesenchymal neoplasia composed of CD34-positive spindle cells. The incidence of this tumour has been estimated between 0.4 and 4.1 patients per million person-years [5][6][7]. The 10-year survival is 99.1%. Negative factors for the unfortunate outcome are higher age, male sex, black race, and anatomic location of the limbs and head [7][8].

Recently, fibrosarcomatous differentiation has been identified as a risk factor for local recurrence [9]. The transformation also increases the rate of metastasis (risk ratio 5.5) and death from disease (risk ratio 6.2) [10]. The fibrosarcomatous transformation is accompanied by an activation of the Akt-mTOR signalling pathway [11]. Treatment of choice is wide tumour excision. Safety margins of 2 cm had a recurrence rate of 1% [12][13][14]. Patients treated with classic or slow Mohs technique have significantly lower recurrence rates [15][16].

DFSP is unresponsive to classical chemotherapy. PDGF-beta, KIT and Abelson murine leukaemia viral oncogene homolog 1 (ABL) inhibitor imatinib mesylate achieved an objective response rate of about 50% in DFSP [17]. In metastatic disease, imatinib mesylate resulted in median survival progression of ≥ 19 months. The fibrosarcomatous transformation had a less favourable outcome [18][20]. Emerging new drug therapies for advanced or metastatic DFSP are multikinase inhibitors pazopanib [21] and regorafenib [22].