PDGFB RNA in situ hybridization for the diagnosis of dermatofibrosarcoma protuberans

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a spindle cell neoplasm of the skin and superficial soft tissue with a tendency for locally aggressive behavior; metastatic potential coincides with fibrosarcomatous transformation. The vast majority of DFSPs harbor the t(17;22) translocation resulting in a COL1A1-PDGFB fusion that drives autocrine growth stimulation via PDGFB overexpression. Here, we examined the utility of PDGFB RNA chromogenic in situ hybridization (CISH) for the diagnosis of DFSP. A total of 337 tumors represented in whole tissue sections and tissue microarrays, including 37 cases of DFSP and 300 histologically similar spindle cell tumors, were subjected to PDGFB RNA CISH using commercially available probes. PDGFB overexpression was observed by light microscopy in 24 of 26 conventional DFSPs (92%) and 11 of 11 fibrosarcomatous DFSPs (100%). One of two DFSPs negative for PDGFB by RNA CISH was found to harbor an uncommon alternative rearrangement involving PDGFD. All examined cases of histologic mimics were negative for PDGFB overexpression; limited PDGFB expression, not reaching an empirical threshold of greater than 5 puncta or one aggregate of chromogen in more than 25% of cells, was observed in 7 of 300 mimics (2.3%), including desmoplastic melanoma, malignant peripheral nerve sheath tumor, angiosarcoma, and pleomorphic dermal sarcoma. Vascular PDGFB expression was seen in several tumor types. We conclude that PDGFB RNA CISH, with careful interpretation and the use of appropriate thresholds, may serve as a surrogate marker of PDGFB rearrangement and a useful ancillary tool for the diagnosis of DFSP.

Figure 1.

Representative photomicrographs of hematoxylin and eosin stain and PDGFB RNA chromogenic in situ hybridization (PDGFB-1 probe set) demonstrating diffuse and strong PDGFB expression in a conventional DFSP with characteristic storiform architecture (A, B). PDGFB expression in DFSP can manifest by RNA chromogenic in situ hybridization as numerous small puncta (C, D) or as larger subcellular aggregates (E, F). Insets represent PDGFB RNA chromogenic in situ hybridization at high magnification.

Figure 2.

Representative photomicrographs of hematoxylin and eosin stain (A), CD34 immunohistochemistry (B), and PDGFB RNA chromogenic in situ hybridization (C, PDGFB-1 probe set) in a fibrosarcomatous DFSP with diffuse and strong PDGFB expression. The COL1A1-PDGFB translocation was identified in this case by targeted next generation sequencing. Inset represents PDGFB RNA chromogenic in situ hybridization at high magnification.

Figure 3.

Representative photomicrographs of hematoxylin and eosin stain (A) and PDGFB RNA chromogenic in situ hybridization in a fibrosarcomatous DFSP comparing the PDGFB-1 (B) and PDGFB-2 (C) probe sets.

Figure 4.

Representative photomicrographs of hematoxylin and eosin stain (A) and PDGFB RNA chromogenic in situ hybridization (B; PDGFB-1 probe set) in a case of PDGFD-rearranged DFSP. Inset represents PDGFB RNA chromogenic in situ hybridization at high magnification.

Figure 5.

Representative photomicrographs of hematoxylin and eosin stain and PDGFB RNA chromogenic in situ hybridization demonstrating a lack of PDGFB expression in cellular dermatofibroma (A, B), solitary fibrous tumor (C, D), and angiomatoid fibrous histiocytoma (E, F). The pictured cases exhibit vascular PDGFB expression in the background. Insets represent PDGFB RNA chromogenic in situ hybridization at high magnification.

Figure 6.

Representative photomicrographs of hematoxylin and eosin stain (A) and PDGFB RNA chromogenic in situ hybridization (B) demonstrating limited PDGFB expression in a case of pleomorphic dermal sarcoma. Inset represents PDGFB RNA chromogenic in situ hybridization at high magnification.