Dermatofibrosarcoma Protuberans With Unusual Sarcomatous Transformation: A Series of 4 Cases With Molecular Confirmation

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a superficial sarcoma of intermediate malignancy usually composed of monotonous short spindle cells with storiform architecture. The tumor cells are diffusely reactive for CD34 and characterized by a translocation involving chromosomes 17 and 22 or a supernumerary ring chromosome that results in the fusion of exon 2 of platelet-derived growth factor beta (PDGFβ; 22q13) to various exons of collagen type 1 alpha 1 (COL1A1; 17q22). In some tumors, fibrosarcomatous transformation can occur and is characterized by a monotonous spindle cell proliferation arranged in fascicles or a herringbone-type pattern. We report 4 DFSPs with unusual and pleomorphic sarcomatous transformation. They occurred on the back, scalp, shoulder, and forehead of women (ages 31,48, 48, and 27 year). In addition to areas of conventional DFSP that strongly expressed CD34, 2 cases showed pleomorphic areas mimicking undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma: 1 case had a patternless area and 1 case had combined round/spindled cells with myxoid areas. Reverse transcription--polymerase chain reaction was performed in 1 case, confirming the presence of a COL1A1-PDGFβ fusion transcript. The remaining three cases were found to be positive for a PDGFβ gene rearrangement by fluorescence in situ hybridization. This series illustrates that sarcomatous transformation in DFSP may occasionally display areas, which can mimic undifferentiated pleomorphic or unclassified sarcoma. Ancillary diagnostic testing may be helpful to confirm the diagnosis, especially in small biopsies.

Dermatofibrosarcoma protuberans with a novel COL6A3‐PDGFD fusion gene and apparent predilection for breast

“…A subset of cases may undergo fibrosarcomatous transformation (fibrosarcoma ex‐dermatofibrosarcoma protuberans) which is associated with frequent local recurrence (58%), as well as metastasis (15%); in addition to areas of conventional dermatofibrosarcoma protuberans, these tumors tend to have a fascicular‐herringbone architecture, and increased cellularity and mitotic activity . Additionally, a pleomorphic variant of dermatofibrosarcoma protuberans has recently been reported . Most tumors exhibit diffuse immunoreactivity for CD34, but this may be diminished‐to‐absent in a proportion of cases with fibrosarcomatous transformation; myoid differentiation is highlighted by smooth muscle actin .…”

“…9 Additionally, a pleomorphic variant of dermatofibrosarcoma protuberans has recently been reported. 10 Most tumors exhibit diffuse immunoreactivity for CD34, 11 but this may be diminished-to-absent in a proportion of cases with fibrosarcomatous transformation 12 ; myoid differentiation is highlighted by smooth muscle actin. 8 Virtually all molecularly characterized cases to date have been reported to have a COL1A1-PDGFB fusion gene.…”

Fibroblastic Connective Tissue Nevus

“…3,26,27 Because FCTN often presents clinically as a plaque-like lesion on the trunk of young patients, involves mainly the skin and the superficial subcutis, and shows positivity for CD34, differentiation between FCTN and plaque-stage DFSP could be problematic, especially when interpreting superficial biopsies. Histologically, DFSP is classically composed of a uniform proliferation of mildly atypical fibroblasts arranged in a storiform pattern, 26,27 which readily distinguishes it from the more disorderly fascicular growth pattern of FCTN. However, in some cases of DFSP, the whorled pattern is very inconspicuous, and the cells can be more randomly or longitudinally oriented, making the distinction from FCTN potentially more challenging.…”

“…In such rare instances, absence of epidermal papillomatous hyperplasia, presence of a hypocellular zone just beneath the epidermis, careful assessment of the uniform but atypical nuclei, and strong diffuse CD34 positivity in lesional cells would favor DFSP. 27 The distinction between DFSP and FCTN is clinically relevant: DFSP is locally aggressive and has a marked tendency to recur locally unless Fibroblastic Connective Tissue Nevus completely excised, whereas FCTN does not seem to recur, even if incompletely excised. Furthermore, DFSP can undergo higher-grade fibrosarcomatous transformation, which has metastatic potential.…”

Current approaches to cutaneous sarcomas: Dermatofibrosarcoma protuberans and cutaneous leiomyosarcoma

“…This is the mechanism being targeted with small molecule tyrosine kinase inhibitor therapy such as imatinib. 25,34,37 Furthermore, detection of this chromosomal aberration by FISH (Fluorescence In Situ Hybridization) represents an invaluable diagnostic tool, particularly in cases of DFSP-FS and other unusual variants, since all of which will exhibit the cytogenetic signature 18,19,21,25,38,39 . Interestingly, this same signature cytogenetic aberration is present in the childhood tumor Giant Cell Fibroblastoma (GCF), with known reported cases showing hybrid DFSP/GCF features.…”