TY - JOUR
T1 - Characterization of novel USP6 gene rearrangements in a subset of so-called cellular fibroma of tendon sheath
AU - Mantilla, Jose G.
AU - Gross, John M.
AU - Liu, Yajuan J.
AU - Hoch, Benjamin L.
AU - Ricciotti, Robert W.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2021/1
Y1 - 2021/1
N2 - Fibroma of tendon sheath (FTS) is an uncommon benign fibroblastic/myofibroblastic neoplasm that typically arises in the tenosynovial tissue of the distal extremities. Histologically, it is a well-circumscribed proliferation of spindle cells within collagenous stroma with peripheral slit-like vessels. Most examples are relatively hypocellular and more densely collagenous than nodular fasciitis; however, a cellular variant has been described, which has considerable morphologic overlap with nodular fasciitis and has been shown to harbor USP6 translocations in a subset of cases. The incidence of these rearrangements and the identity of the USP6 fusion partners have not been described in detail. In this study we evaluate 13 cases of cellular fibroma of tendon sheath by anchored multiplex PCR/next generation sequencing in order to detect potential gene fusions. Nucleic acids of adequate quality were obtained in 11 cases, demonstrating gene fusions in 7/11 (64%), all of which involve USP6 with a variety of partners, including PKM, RCC1, ASPN, COL1A1, COL3A1, and MYH9. Some unusual histomorphologic findings were present in a subset of cases including palisading growth pattern, epithelioid cells, and osteoclast-like multinucleated giant cells, particularly in the tumors with PKM and ASPN gene partners. Overall, the findings support a biologic relationship between cellular fibroma of tendon sheath and other lesions within the spectrum of USP6-rearranged neoplasms, particularly nodular fasciitis.
AB - Fibroma of tendon sheath (FTS) is an uncommon benign fibroblastic/myofibroblastic neoplasm that typically arises in the tenosynovial tissue of the distal extremities. Histologically, it is a well-circumscribed proliferation of spindle cells within collagenous stroma with peripheral slit-like vessels. Most examples are relatively hypocellular and more densely collagenous than nodular fasciitis; however, a cellular variant has been described, which has considerable morphologic overlap with nodular fasciitis and has been shown to harbor USP6 translocations in a subset of cases. The incidence of these rearrangements and the identity of the USP6 fusion partners have not been described in detail. In this study we evaluate 13 cases of cellular fibroma of tendon sheath by anchored multiplex PCR/next generation sequencing in order to detect potential gene fusions. Nucleic acids of adequate quality were obtained in 11 cases, demonstrating gene fusions in 7/11 (64%), all of which involve USP6 with a variety of partners, including PKM, RCC1, ASPN, COL1A1, COL3A1, and MYH9. Some unusual histomorphologic findings were present in a subset of cases including palisading growth pattern, epithelioid cells, and osteoclast-like multinucleated giant cells, particularly in the tumors with PKM and ASPN gene partners. Overall, the findings support a biologic relationship between cellular fibroma of tendon sheath and other lesions within the spectrum of USP6-rearranged neoplasms, particularly nodular fasciitis.
UR - http://www.scopus.com/inward/record.url?scp=85087794206&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087794206&partnerID=8YFLogxK
U2 - 10.1038/s41379-020-0621-1
DO - 10.1038/s41379-020-0621-1
M3 - Article
C2 - 32661296
AN - SCOPUS:85087794206
SN - 0893-3952
VL - 34
SP - 13
EP - 19
JO - Modern Pathology
JF - Modern Pathology
IS - 1
ER -