Dermatofibrosarcoma Protuberans

The American Joint Committee on Cancer (AJCC) or Union for International Cancer Control (UICC) TNM system can be applied for fibrosarcomatous DFSP.

DFSP is characterized by the presence of supernumerary ring chromosomes that contain the centromere of chromosome 22 and comprise interspersed sequences from chromosomes 17 and 22. Additional aberrations, such as trisomy 5 and trisomy 8, are also observed. Unbalanced t(17;22)(q21.3;q13.1) translocations are present in most children and rarely in adults. Most DFSP cells harbor not only a structural rearrangement but also a gain of 17q21.3-17qter and 22q10-q31 sequences. Both ring and der(22)t(17;22) chromosomes contain a chimeric gene fusing COL1A1 at 17q21.33 with PDGFB at 22q13.1. The breakpoint in COL1A1 is variable: the chimeric gene is composed of at least the first 6 exons up to exon 49 of COL1A1 and a consistent fragment retaining all but exon 1 of the PDGFB gene. Fewer than 5% of typical DFSP cases are negative for the COL1A1-PDGFB fusion gene by routine molecular testing; alternative COL6A3-PDGFD and EMILIN2-PDGFD fusion genes have been identified, and in some cases, COL1A1-PDGFB rearrangement is cryptic. The COL1A1-PDGFB fusion gene encodes a fusion protein that is proteolytically processed to normal PDGFB ligand. Because tumor cells express the PDGFRB receptor on their cell surfaces, autocrine stimulation of neoplastic cells drives tumorigenesis. This molecular pathway provides a rationale for targeted therapy with tyrosine kinase inhibitors for unresectable DFSP or metastatic fibrosarcomatous DFSP. Alteration of the PDGFRB/AKT/mTOR pathway is seen in fibrosarcomatous DFSP.

DFSP lesions are indurated plaques with one or multiple nodules. Multiple protuberant tumors are often seen in recurrent lesions. These ill-defined and infiltrative neoplasms have firm, greyish-white cut surfaces with occasional gelatinous areas, whereas areas of tumor necrosis are only rarely observed.

Classic DFSP is characterized by a diffuse infiltration of dermis and subcutis. The neoplastic cells infiltrate the subcutaneous fat, resulting in a typical honeycomb appearance. The epidermis is usually uninvolved, and tumor cells encase skin appendages without destroying them. DFSP is composed of cytologically uniform spindled tumor cells containing plump or elongated wavy nuclei arranged in storiform, whorled, or cartwheel growth patterns. Cytological atypia is minimal, and mitotic activity is low. The collagenous stroma contains small blood vessels. The superficial portion of the neoplasm may be less cellular, causing considerable challenges in the differential diagnosis on small biopsies. Rarely, cases of DFSP present as a subcutaneous mass with infiltration of deep soft tissues. Rare cases may show prominent vessels, granular cell change, prominent nuclear palisading, and Verocay body formation.

Pigmented DFSP (also known as Bednar tumor) contains a variable number of pigmented, dendritic melanocytic cells.

Myxoid DFSP may show prominent myxoid stroma with a more nodular growth and numerous vessels with slightly fibrotic vessel walls, often producing a more variable architecture, which may mimic other myxoid mesenchymal neoplasms.

DFSP with myoid differentiation shows bundles and nests of spindled myofibroblastic tumor cells, more often in the fibrosarcomatous subtype.
Plaque-like DFSP may show a flat, plaque-like growth resembling benign plaque-like CD34-positive dermal fibroma.

Fibrosarcomatous DFSP represents morphological progression to a usually fascicular pattern, with acquisition of metastatic potential. The fibrosarcomatous component often shows a nodular, rather well-circumscribed growth and is composed of cellular spindle cell fascicles with a herringbone appearance. The neoplastic cells in fibrosarcomatous areas are characterized by increased atypia and proliferative activity.

By immunohistochemistry, tumor cells stain positively for CD34 and may show expression of EMA. Importantly, fibrosarcomatous DFSP can show loss of CD34 expression in about half of the cases. Tumor cells in myoid nodules and bundles stain strongly for SMA.

Not clinically relevant

DFSP is characterized by locally aggressive growth and frequent, often repeated local recurrences unless widely excised. The rate of local recurrences varies from 20% to 50% in the setting of inadequate margins. In contrast, ordinary DFSP almost never metastasizes. Higher-grade fibrosarcomatous progression is seen in 5% of cases. Fibrosarcomatous DFSP exhibits more aggressive behavior than ordinary DFSP, and 10–15% of patients develop distant metastases, most often to the lungs. Histological grading has not been shown to be prognostic in fibrosarcomatous DFSP.

For histologically challenging cases and for tumors composed entirely of fibrosarcomatous DFSP without a conventional component, detection of COL1A1-PDGFB can be used to confirm the diagnosis. However, the COL1A1-PDGFB fusion may be cryptic in about 2% of cases, and another 2% of cases harbor alternative fusions involving PDGFD.

Essential: a storiform architecture and uniform spindle cell morphology; diffusely infiltrative growth with a honeycomb pattern in the subcutis; expression of CD34; fibrosarcomatous DFSP: fascicular architecture with increased mitotic activity.

Desirable: COL1A1-PDGFB gene fusion or rarely alternative PDGFD rearrangements (in selected cases).