Abstract and Introduction

Abstract
A female patient with progressive systemic sclerosis and pulmonary fibrosis had a dermatofibrosarcoma protuberans on the right thigh. After resection of the tumor, new lesions occurred in the scar, and wide excision was repeated. Two years later, a lung metastasis was discovered, and segmental resection was done. After 1 year of follow-up, no local recurrences or metastases were found.

Introduction
Dermatofibrosarcoma protuberans (DFSP) is a tumor of intermediate malignancy that rarely metastasizes but has a high incidence of local recurrence.[1] Although the lung is the most frequent site of metastasis, there are only a few reports of surgical excision of pulmonary metastases, and cure has rarely been achieved despite resection.[2] We report the case of a female patient with a lung metastasis of DFSP, who was well 1 year after segmental lung resection.

Case Report
A 63-year-old woman had had progressive systemic sclerosis with pulmonary fibrosis since 1986 and had been treated over the years with cyclosporine and prednisolone. In 1992, she noticed a 2 cm red-brown macule on the right thigh. A dermatologist believed it to be a histiocytoma. Three years later (1995), the lesion measured 4 cm and had a nodular surface with ulcerations. A biopsy specimen revealed DFSP, and a wide excision with resection of the subcutaneous tissue and the underlying fascia was done. The histologic examination showed spindle cells in a storiform pattern, as well as multinucleated tumor giant cells and few mitotic figures. The margins were free of tumor, and no metastases were found. In 1997, new lesions occurred in the scar of the former operation. Wide excision and reconstructive procedures with a myocutaneous rotational flap were repeated. Histologic examination showed the same proliferation of spindle cells as in 1995. The margins were tumor-free, and again no metastases were found. Immunosuppressive treatment with cyclosporine was stopped, but prednisolone therapy was continued at 5 mg/day. Two years later, a chest radiograph showed a 3 cm tumor in the right upper lobe (Fig 1), and segmental resection was done. Pathologic examination revealed metastasis of the DFSP. The cells showed a typical storiform pattern (Fig 2) but with a higher mitotic activity and more atypia than in the previous lesions. All margins were adequate. After 1 year of follow-up, the patient was well, and no local recurrences or metastases had been found.

Figure 1. (click image to zoom) Metastasis of dermatofibrosarcoma protuberans in right upper lobe.

Figure 2. (click image to zoom) Lung metastasis of dermatofibrosarcoma protuberans with typical storiform pattern of spindle cells. (Hematoxylin-eosin, original magnification x 100)

Discussion
Dermatofibrosarcoma protuberans was first described by Darier and Ferrand in 1924 and named by Hoffmann in 1925.[3] The tumor usually occurs in adults from 20 to 50 years old and begins as nonprotuberant plaque that is indolent and violaceous or red-brown. The lesion can develop protuberant nodules and even ulcerate, as in our patient.[1] The most common location is the trunk (62%), followed by the extremities (25%) and the head and neck regions (13%). Most local recurrences, which can occur in 20% to 49% of cases are noted within the first 3 years after excision, but late recurrence has been reported as well.[2] The recurrence rate is highest in DFSP of the head and neck because of cosmetic and functional restrictions of resecting large areas.[2] The greater the number of recurrences the more likely the tumor is to disseminate.[2] Metastases are rare. A review of 913 cases of DFSP described regional lymph node metastases in about 1% and distant metastases in approximately 4%.[2] The lungs are the most frequent site of metastases, but metastases to brain, bone, and heart have also been reported.[4] Metastases usually in cases occur within 6 years.[3] The prognosis in cases of metastasis is poor because death often ensues within 1 year after detection of metastatic disease.[3] Apart from this report, there is only one other report on a patient being well after resection of a lung metastasis. Gloster et al[5] reported two separate episodes of pulmonary metastasis 9 and 10 years, respectively, after initial DFSP. The first lung metastasis was treated by wedge resection. After the second relapse, pneumonectomy was done, followed by postoperative radiation, and the patient remained free of disease for 5 years. Gloster[2] described three other cases of surgical excision of lung metastases, but cure was not achieved in any patient. Lai et al[6] described a renal transplant recipient with DFSP similar to other sarcomas that have been reported as complications of organ transplantation and immunosuppression. Thus, the immunosuppressive treatment may have facilitated the development, relapse, and dissemination of DFSP in our patient.

Histologically, DFSP is characterized by a proliferation of spindle cells embedded in collagen[2] and arranged in a storiform or cartwheel pattern.[4] Dermatofibrosarcoma protuberans grows in fingerlike projections away from the primary tumor.[1] There are several variants of DFSP. The so-called Bednar tumor (5% of all cases) is a pigmented variant.[4] The presence of fibrosarcomatous change characterized by a replacement of the storiform morphology by a dense herringbone pattern of the spindle cells[7] with a high rate of mitoses indicates a heightened rate of local recurrences.[2,4] Cytogenetic studies of DFSP cells recently revealed specific chromosomal abnormalities as supernumerary ring chromosomes containing chromosome 17 and 22 sequences, abnormal clones, and translocations.[2,8] The gene rearrangements fuse the collagen type I A1 (COL1A1) protein gene on chromosome 17 with the platelet-derived growth factor ß chain (PDGFB) on chromosome 22; PDGFB is a potent mitogen and has been implicated in transforming processes via autocrine and paracrine pathways. These gene fusions delete exon 1 of PDGFB and release this growth factor from its normal regulation.[9]

The rate of recurrence of DFSP after traditional surgery is high (49% to 53%) because of the microscopic extension of the tumor and inadequate removal.[4] When wide excision is used, with margins of 3 cm, the recurrence rate drops to 10% to 20%.[4] Mohs micrographic surgery offers the advantage of tissue sparing with microscopic control of the surgical margins to minimize the destruction of healthy tissue.[7] Because of a low recurrence rate (0% to 6.6%), Mohs micrographic surgery is the treatment of choice.[2,4] The adequacy of the initial resection is reported to be the most important prognostic factor.[2] Inadequate excision is thought to open vascular channels and permit metastatic spread. Since lymph node metastasis is rare, prophylactic dissection of regional lymph nodes is not required.[3] Radiation can be an effective primary treatment when the lesions are not resectable[3] or a postoperative therapeutic option when complete excision has not been possible.[2] Other reports about radiotherapy have shown no response.[7] Radiation may induce malignant behavior of DFSP and can be a risk of promoting aggressive sarcomatous transformation.[2,5] Because of the tumor-free margins of the lung metastasis and because of the pulmonary fibrosis, we did not use postoperative radiation in our patient.

During the first 3 years after excision of DFSP, examinations are recommended every 3 to 6 months and annually thereafter for life.[2] Chest films are indicated yearly during a follow-up period up to 10 years.[3] We believe this is first reported case of progressive systemic sclerosis, pulmonary fibrosis, and dermatofibrosarcoma protuberans metastatic to the lung.

The variability of human beings in their illnesses and their reactions to them is a fundamental reason for the planned clinical trial and not against it. -- Austin Bradford Hill, Principles of Medical Statistics, 1971

Reprint Address
Reprint requests to Gerald W. Westermann, MD, Medizinische Poliklinik D, Albert-Schweitzer-Str 33, 48149 Münster, Germany.

Gerald W. Westermann, MD, Horst Buerger, MD, Ulrike Kappes, MD, Fritz Matzkies, MD, Klaus Kisters, MD, Departments of Internal Medicine D and Pathology, Westfälische Wilhelms-University, Münster, and St. Anna-Hospital, Herne, Germany