Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool

Abstract

Dear Editor, Nodular fasciitis is a lesion that is well known for posing a diagnostic challenge to pathologists. The clinical presentation of sudden onset and fast growing rate of this soft tissue lesion along with histological features, comprising a poorly demarcated cellular myofibroblastic mitotically active lesion, frequently raises concern of malignancy. There are no specific immunohistochemical markers for nodular fasciitis and the diagnosis, until recently, was based on histological features alone. The age of occurrence and anatomical site are unhelpful in making the diagnosis as these lesions can occur at any age and at any anatomic soft tissue site, although the most frequent site is the forearm and the trunk and is more common in young adults [5]. These lesions have traditionally been considered reactive in nature because if unresected, they may involute and are not associated with malignant transformation. If the patient is quizzed, a history of trauma to the site of tumour may be obtained. In 2004, a USP6 gene rearrangement (chromosome 17p13) was identified in aneurysmal bone cysts [2, 3]. This rearrangement has been associated with a variety of fusion partners including CDH11, ZNF9, COL1A1, TRAP150 and OMD [3]. In 2011, it was also reported that nodular fasciitis harboured a USP6 rearrangement; however the most common fusion partner, MYH9 in chromosome 22q12.3, found in 65 % of cases of nodular fasciitis has not been reported in aneurysmal bone cysts [1]. We therefore set out to determine the incidence of USP6 gene rearrangements in a series of cases of nodular fasciitis diagnosed at our service in order to incorporate this test as an ancillary diagnostic tool for this lesion. Thirty-four cases, previously diagnosed as nodular fasciitis, were selected from our files. All cases were analysed by fluorescence in situ hybridisation (FISH) using custom-made break-apart BAC probes as previously described [1]. Material was available from 28 of these cases for analysis by RT-PCR for MYH-USP6 fusion transcript using previously published primers sets [1]. Thirty-one cases including 1 reactive tonsil, 5 B cell lymphomas, 9 PNET/Ewing sarcoma, 5 desmoidtype fibromatoses, 5 myxoid liposarcomas and 6 synovial sarcomas were selected as negative controls. All control samples were diagnosed in conjunction with their characteristic genetic alteration. In addition, 16 cases of primary aneurysmal bone cyst were tested. The presence of break-apart signals was assessed in ‘hot spots’ tumour-rich areas where 50 nonoverlapping nuclei were scored. Cases were classified as positive for USP6 gene rearrangement when 15 %, or above, of cells harboured the break-apart signal. All 34 cases of nodular fasciitis analysed by FISH, and 21 of the 28 cases tested by RT-PCR were informative. Ninety-one percent (31/34) of the cases initially diagnosed as nodular fasciitis showed a clear USP6 gene rearrangement by FISH in more than 15 % of the cells (range, 15–80 %; mean, 35.6 %) (Fig. 1). This result confirms the data of Erickson-Johnson et al. reporting USP6 gene rearrangement in 92 % of the cases [1]. M Fernanda Amary and Hongtao Ye contributed equally to this study.