USP6 Gene Rearrangement in Spindle Cell Neoplasms: A Diagnostic Tool for Nodular Fasciitis

2013-09-16 22:08:11

Society for Pediatric Pathology; 2013; DOI:

MR Conces, SL Cook, EB Stelow, RD LeGallo



Nodular fasciitis (NF), once thought to be a reactive proliferation, has recently been characterized by a recurrent translocation involving USP6, which is seen in approximately 90% of cases. NF is a benign lesion but may be misdiagnosed as a more locally aggressive or even a malignant neoplasm. We sought to assess the utility of the USP6 gene rearrangement to differentiate nodular fasciitis from other spindle cell lesions within the differential diagnosis, focusing on those that occur in childhood.


Tissue microarrays using duplicate cores were constructed from 73 archival formalin-fixed, paraffin-embedded cases that included diagnoses of NF (10), myofibroma (8), ischemic fasciitis (1), cranial fasciitis (1), inflammatory myofibroblastic tumor (4), desmoid tumor (8), fibroma of tendon sheath (8), benign fibrous histiocytoma (8), infantile fibrosarcoma (1), fibrous hamartoma of infancy (8), neurofibroma (8), lipofibromatosis (4), low-grade myofibroblastic sarcoma (1), low-grade fibromyxoid sarcoma (1) and spindle cell rhabdomyosarcoma (2). Fluorescent in situ hybridization (FISH) was performed using the USP6 dual color break apart probe at 17p13.2 (Empire Genomics, New York) according to an established protocol. A total of 100 tumor cells from each case were scored. Rearrangement was defined by the orange and green signal being at least one signal width apart. A tumor was considered rearranged if >10% of tumor cells
showed disrupted USP6.


There were 32 males and 41 females with an age range from 3 days to 81 years (71% δ 18 yrs, mean age= 17 yrs, median age= 14 yrs). All cases aside from one case each of fibrous hamartoma of infancy, fibroma of tendon sheath and neurofibroma were informative by FISH. The USP6 gene was disrupted in 7 cases and intact in 3 cases that were originally diagnosed as NF. The USP6 gene was intact in all other diagnoses. On review of all the cases of NF, the three cases that were intact did not show all of the classic diagnostic features and all had included a note stating such.


This study showed that the USP6 gene rearrangement is present in 70% of our cases diagnosed as NF. The USP6 gene rearrangement was not seen in the histologic
mimics, which supports it’s usefulness as a diagnostic marker. The study also supports that the histologic spectrum of NF may be quite limited and in cases with atypical features, the diagnosis should be molecularly confirmed.

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