USP6 Fusion Partners Identified by Next Generation Sequencing in Nodular Fasciitis and Cellular Fibroma of Tendon Sheath: An Institutional Experience

Document Type

Conference Proceeding

Publication Date

3-19-2022

Publication Title

Mod Pathol

Abstract

Background: Nodular fasciitis (NF) is a self-limited proliferation of fibroblasts and myofibroblasts often arising in subcutaneous tissues in the upper extremities, head, neck, and trunk. Fibroma of tendon sheath (FTS) is a myofibroblastic proliferation usually seen in association with tenosynovial tissue in the digits or hand. Both NF and FTS exhibit rearrangements of the USP6 gene. While the majority of NF exhibit a MYH9-USP6 fusion transcript, only a minority of FTS cases have been shown to contain MYH9 as a USP6 fusion partner. We aim to assess the identity and distribution of USP6 fusion partners in NF and FTS on which NGS was performed within our institution. Design: An LIS search was performed for NF and FTS from years 2017-21 with available ancillary sequencing studies. In these cases, RNA was extracted using standard protocols for formalin fixed paraffin embedded tissues (minimum 20 ng RNA). RNA sequencing was performed using Archer Fusion Sarcoma panel using primers flanking exons 1-3 of the USP6 gene. Assay acceptability criteria included minimum depth of coverage 200X for RNA assays and percent uniformity of coverage >70%. Other RNA panel quality matrix included Reads After Trimming > 2,000,000 and average unique RNA start sites per GSP2 Control >= 10. Results: The initial language search resulted in 20 cases with a diagnosis of NF or FTS. Of these, RNA sequencing was performed on 13 cases. 7 of 13 cases were positive for a USP6 gene fusion. Basic patient demographics, diagnoses and sequencing findings are presented in Table 1. Of the USP6 fusion positive cases, 6 were NF, and 1 was FTS. 4/7 were males with a median age 20 years (range 7 to 57), and median size 2.5 cm (range 1.0 to 5.5). Fusion partners were COL1A1, MYH9, SPARC, CTNNB1, RUNX2, HDLBP, and RRBP1. Conclusions: While the MYH9 gene was the most common partner for USP6 in this study, the MYH9-USP6 transcript was present in less than half of this limited cohort. To our knowledge, the HDLBP-USP6 fusion identified represents a yet undescribed fusion in NF. Furthermore, while a SPARC-USP6 fusion transcript has been previously identified in a conventional FTS, we report a SPARCUSP6 fusion in a cellular FTS, illustrating the morphologic and molecular diversity of these lesions. Assessment for USP6 rearrangement has proven an invaluable tool for the diagnosis of both FTS and NF. While this institutional series is limited, the findings further attest to the expanding diversity of USP6 fusion partners in these entities. (Table Presented).

PubMed ID

Not assigned.

Volume

35

Issue

SUPPL 2

First Page

62-63

Last Page

63

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