53. USP6 gene rearrangement in nodular fasciitis

Shin, Christina; Low, Irene; Ng, Daniel; Oei, Paul; Miles, Carina; Symmans, Pennie

doi:10.1097/01.pat.0000461662.31964.93

Cited by 8 publications

(10 citation statements)

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“…However, break-apart fluorescence in situ hybridization (FISH) for MYH9 showed balanced rearrangement in only 31/48 cases. Additional studies using FISH for USP6 rearrangement have shown a sensitivity of 83-93% [17][18][19][20] and a specificity of 100%. 18,20 In contrast, RT-PCR yielded only 53-74% sensitivity.…”

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confidence: 99%

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

et al. 2017

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Nodular fasciitis is a self-limited myofibroblastic lesion that can be misdiagnosed as a sarcoma as a result of its rapid growth, cellularity, and sometimes prominent mitotic activity. A recurrent translocation t(17;22) has been identified in nodular fasciitis, fusing the coding region of USP6 to the promoter region of MYH9, and resulting in increased USP6 expression. A subset of cases show USP6 rearrangement without the typical fusion variants by RT-PCR, or any MYH9 rearrangement by FISH. We sought to further characterize such tumors using molecular diagnostic assays. A novel RT-PCR assay was designed to detect the two known MYH9-USP6 fusion types in formalin-fixed paraffin-embedded and frozen tissue, and a break-apart FISH assay was designed to detect USP6 rearrangement. Twenty-six cases of nodular fasciitis diagnosed between 2002 and 2013 were retrieved from the pathology files of our institutions and were confirmed to be positive by FISH and/or RT-PCR. Seven samples showed USP6 rearrangement by FISH but were negative for MYH9-USP6 fusion by RT-PCR; these cases were subjected to a next-generation sequencing assay utilizing anchored multiplex PCR technology. This assay targets a single partner gene associated with fusions in bone and soft tissue tumors for agnostic detection of gene fusion partners. Novel fusion partners were identified in all seven cases and confirmed by RT-PCR. Structurally, all fusions consisted of the juxtaposition of the entire coding region of USP6 with the promoter of the partner gene, driving increased USP6 expression. This study confirms the neoplastic nature of nodular fasciitis, defines additional pathogenic fusion partners, and adds to the growing body of literature on USP6-associated neoplasia. Given the diagnostic challenges of these tumors, molecular assays can be useful ancillary tools; however, the prevalence of promoter swapping must be recognized when interpreting results.

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confidence: 99%

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

et al. 2017

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“…It is of note that nodular fasciitis also shares with pseudosarcomatous myofibroblastic proliferation of the urinary tract an incomplete association with preceding trauma. Therefore, in soft tissue tumour pathology, evaluation for USP6 rearrangement may be a potentially helpful technique to resolve challenging diagnostic cases . Interestingly, rearrangement of the USP6 locus is also shared by aneurysmal bone cyst, which is histologically quite different, although perhaps less so if one considers the bland spindle‐shaped cell component of aneurysmal bone cyst to be the true neoplastic cell population.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in soft tissue tumour pathology, evaluation for USP6 rearrangement may be a potentially helpful technique to resolve challenging diagnostic cases. 19 Interestingly, rearrangement of the USP6 locus is also shared by aneurysmal bone cyst, 20 which is histologically quite different, although perhaps less so if one considers the bland spindle-shaped cell component of aneurysmal bone cyst to be the true neoplastic cell population. Despite the histological, immunophenotypic, and ultrastructural 16,21,22 similarities between pseudosarcomatous myofibroblastic proliferation of the genitourinary tract and nodular fasciitis, we found that these lesions lacked USP6 rearrangement ( Figure 1D), which refutes our hypothesis that this may be its visceral equivalent.…”

Section: Discussionmentioning

confidence: 99%

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

et al. 2018

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Despite overlap in histological and immunohistochemical features between pseudosarcomatous myofibroblastic proliferation and nodular fasciitis, these tumours lack the recently recognised USP6 rearrangements that occur in nodular fasciitis, as well as alternative fusions found in ALK-negative inflammatory myofibroblastic tumours. At present, this diagnosis remains based primarily on clinical, histological and immunohistochemical features.

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“…USP6 FISH testing was negative in our patient which raises the possibility of nodular fasciitis-like granulation tissue as an alternative diagnosis. USP6 testing is negative in 10 to 14% of nodular fasciitis cases, so FISH testing is not a sensitive enough test to exclude the diagnosis of nodular fasciitis [13,14]. Pseudoepitheliomatous hyperplasia that develops in skin cancer excision sites is an analogous problem, because it is a reactive process that can be mistaken for squamous cell carcinoma at the time of reconstruction [15].…”

Section: Discussionmentioning

confidence: 99%

Nodular fasciitis complicating a staged surgical excision of dermatofibrosarcoma protuberans

2016

Journal of the American Academy of Dermatology

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Dermatofibrosarcoma protuberans (DFSP) is an unusual spindle cell tumor with a high rate of local recurrence with traditional excision. Fortunately, Mohs micrographic surgery yields excellent cure rates for this neoplasm due to contiguous tumor spread and meticulous tumor mapping and margin analysis. We present the unique case of a patient treated with a modified Mohs technique with an analysis of the final margin with permanent sections, who developed a spindle cell neoplasm in the margins of her second stage excision consistent with nodular fasciitis. Distinguishing residual DFSP from a benign reactive process was an essential and challenging component of this patient's management.

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53. USP6 gene rearrangement in nodular fasciitis

Cited by 8 publications

References 0 publications

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

USP6 activation in nodular fasciitis by promoter-swapping gene fusions

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Nodular fasciitis complicating a staged surgical excision of dermatofibrosarcoma protuberans

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