USP6-rearranged soft tissue neoplasms

Clinicopathologic and molecular characterization of USP6-rearranged soft tissue neoplasms: The evidence of genetic relatedness indicates an expanding family with variable bone-forming capacity.:

Clinicopathologic and molecular characterization of USP6-rearranged soft tissue neoplasms: The evidence of genetic relatedness indicates an expanding family with variable bone-forming capacity.

Histopathology. 2020 Sep 30;:

Authors: Wang JC, Li WS, Kao YC, Lee JC, Lee PH, Huang SC, Tsai JW, Chen CC, Chang CD, Yu SC, Huang HY

Abstract

AIMS: USP6 rearrangement underpins self-limiting fibroblastic/myofibroblastic neoplasms, including nodular fasciitis (NF), myositis ossificans (MO), aneurysmal bone cyst (ABC) and related variants. We characterized UPS6 and fusion partners to delineate the clinicopathologic, genetic, and bone-forming features in such lesions of soft tissue (ST).

METHODS AND RESULTS: Break-apart FISH validated USP6 rearrangement in 31/35 NFs (containing 3/3 fasciitis ossificans [FO]), 7/8 cellular variants of fibroma of tendon sheath (C-FTSs), 4/6 MOs, 3/3 ST-ABCs, and 2/2 fibro-osseous pseudotumor of digits (FOPD). By FISH and RT-PCR, MYH9-USP6 was the commonest fusion in 4 C-FTSs and 20 NFs, including 1 intravascular and 2 infantile (1 retroperitoneal) cases. MYH9-USP6 fusion confirmed the diagnosis of 2 NFs >5 cm with prominent ischemic necrosis. COL1A1-USP6 fusion was predominant in ossifying lesions, including all FOs, MOs, ST-ABCs, and FOPDs with identified partner genes, and also present in non-ossifying head and neck NFs (HN-NFs) and C-FTSs in 2 cases each. A cervical NF of a 14-month-old girl harbored the novel COL1A2-USP6 fusion. Ossifying lesions exhibited considerable genetic and morphologic overlaps. Sharing COL1A1-USP6 fusion, FO and FOPD exhibited similar central or haphazard bone matrix deposition. Besides zonation of outward bone maturation, 4 COL1A1-USP6-positive MOs had incipient to sieve-like pseudocysts reminiscent of ST-ABC.

CONCLUSION: MYH9-USP6 fusion is present in some C-FTSs and most NFs, including rare variants, but unrelated to bone formation. All bone-forming USP6-rearranged lesions adopt COL1A1 as the 5' partner, indicating close genetic kinships. However, COL1A1/COL1A2 also contributes to the pathogenesis of minor subsets of non-ossifying USP6-rearranged HN-NFs and C-FTSs.



PMID: 33000481 [PubMed - as supplied by publisher]