Dermatofibrosarcoma protuberans: from translocation to targeted therapy

Abstract

Dermatofibrosarcoma protuberans (DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery (MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13) (COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management.

Keywords: Dermatofibrosarcoma protuberans (DFSP); Mohs micrographic surgery (MMS); imatinib; targeted therapy; translocation.

Figure 1

A large polypoid nodule is presented with a homogeneous firm yellowish white cut surface. The tumor can be seen to expand the entire dermis, and extends into the more superficial subcutis.

Figure 2

(A) Dermatofibrosarcoma protuberans (DFSP). Ill-defined cellular tumor is present within the superficial dermis, close to the squamous epithelium (top left of field) (H&E staining, 20×). (B) Most DFSP infiltrates the dermis and subcutis, but some are deeply infiltrating. This example shows prominent infiltration of skeletal muscle bundles (lower half of field) (H&E staining, 20×). (C) DFSP typically comprises cellular distributions of bland spindle cells with elongated vesicular nuclei and small amounts of fibrillary cytoplasm, in a prominent storiform or ¸cartwheel̓ pattern (H&E staining, 200×). (D) Immunohistochemically, DFSP characteristically shows diffuse and strong expression of CD34. This example also illustrates the linearly oriented tumor strands that infiltrate the subcutaneous fat in a ¸honeycomb̓ pattern (IHC staining, 100×). (E) Tumors may show focal or sometimes prominent myxoid change. As the characteristic storiform architecture is lost, there may be difficulty in establishing a diagnosis of DFSP (H&E staining, 100×). (F) Bednar tumor is characterized by spindle cells in a storiform pattern in which there are scattered pigmented, dendritic melanocytic cells (H&E staining, 400×). (G) In children, giant cell fibroblastoma (GCF) is considered a variant of DFSP, but GCF are typically hypocellular, with bland spindle cells and interspersed tumor giant cells in patternless distributions within myxoid or collagenous stroma (H&E staining, 400×). (H) In fibrosarcomatous transformation, the cells are present in more loosely fascicular distributions or ¸herringbone̓ patterns, and often show more prominent mitotic activity (H&E staining, 100×).