Soft-tissue aneurysmal bone cyst with translocation t(17;17)(p13;q21) corresponding to COL1A1 and USP6 loci

Abstract

We present the case of a 46-year-old woman with no significant past medical history who developed left mid-thigh pain and fullness. Imaging demonstrated a mineralized soft-tissue mass, which increased in size during a year of monitoring, but retained a circumscribed appearance. The mass was located in the medial soft tissues of the thigh, separate from the bone on imaging studies, and this finding was confirmed during excision. The mass showed gross and microscopic features of an aneurysmal bone cyst. This diagnosis was supported by cytogenetic analysis revealing a t(17;17)(p13;q21) translocation corresponding to the USP6 and COL1A1 loci. Soft-tissue aneurysmal bone cyst is a rare entity, with fewer than 25 reports in the literature. Limited cytogenetic information about these tumors is available. To our knowledge, the USP6 and COL1A1 rearrangement has only previously been described in a pediatric soft-tissue aneurysmal bone cyst. We also discuss the differential diagnosis of ossifying soft-tissue lesions.

Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst

“…NGS‐based analyses have not only shown the universal presence of USP6 gene rearrangement in primary ABCs, but also revealed several novel fusion partners. Hitherto, 14 different USP6 fusion partners have been identified: CDH11 , CNBP , COL1A1 , CTNNB1 , EIF1 , FOSL2 , OMD , PAFAH1B1 , RUNX2 , SEC31A , SPARC , STAT3 , THRAP3 and USP9X , with the CDH11‐USP6 fusion being the most common (reported in 19% and 38% of cases in two series) . In this study, we describe four novel fusion partners of the USP6 gene: FAT1 , TNC , ASAP1 , and SAR1A .…”

“…A specific fusion partner does not seem to influence the structure of the USP6 gene product, but rather the level of its overexpression. From our and other recent small series of ABCs, it is not possible to draw conclusions about the clinical or pathologic significance of different fusion partners . Large studies with longer follow‐up are needed to determine whether specific fusion partners lead to specific morphologic features of ABCs, are associated with particular locations in the skeleton or determine biologic behavior …”

“…USP6 gene rearrangements have been identified in tumors other than bone ABCs, including nodular fasciitis, soft tissue ABCs, fibro‐osseous pseudotumor of digits and myositis ossificans . In nodular fasciitis, MYH9‐USP6 fusion is present in the majority of cases and other fusions reported include COL6A2‐USP6 , CALU‐USP6 , CTNNB1‐USP6 , MIR22HG‐USP6 , RRBP1‐USP6 , SPARC‐USP6 , and THBS2‐USP6 .…”

“…In nodular fasciitis, MYH9‐USP6 fusion is present in the majority of cases and other fusions reported include COL6A2‐USP6 , CALU‐USP6 , CTNNB1‐USP6 , MIR22HG‐USP6 , RRBP1‐USP6 , SPARC‐USP6 , and THBS2‐USP6 . In soft tissue ABC, fibro‐osseous pseudotumor of digits and myositis ossificans, only COL1A1‐USP6 fusion has been identified so far . Nevertheless, all these lesions probably represent a spectrum of tumors, driven by USP6 gene rearrangements, with the diversity of fusion partners seemingly being the biggest in bone ABCs.…”

“…There is a growing list of known fusion partners, of which CDH11 seems to be the most frequent; it was detected in 19% and 38% of ABCs in two series . Other fusion partners identified so far include CNBP , COL1A1 , OMD and THRAP3 , CTNNB1 , E1F1 , FOSL2 , PAFAH1B1 , RUNX2 , SEC31A , STAT3 , SPARC and, most recently, USP9X . Despite different fusion partners, all USP6 rearrangements seem to function by a promoter swap mechanism, resulting in oncogenic activation of USP6 and subsequent ABC formation .…”