USP6‐associated neoplasm as a tentative subset of postoperative spindle cell nodule.

Aim: Postoperative spindle cell nodule (PSCN) is a pseudosarcomatous proliferative lesion of unclear molecular genetic origins. Methods and results: We examined seven patients with PSCN, using routine haematoxylin–eosin (H&E) slide preparations and a series of immunostains. The latter targeted keratin, vimentin, α‐smooth muscle actin (SMA), anaplastic lymphoma kinase (ALK [D5F3]), and other proteins. Ubiquitin‐specific peptidase 6 (USP6) and anaplastic lymphoma kinase (ALK) gene rearrangements were also analysed by fluorescence in situ hybridization (FISH). There were histories of prior surgical intervention (n = 6) or trauma (n = 1) in all seven patients. All lesions were highly cellular and mitotically active spindle cell proliferations, with no cytologic atypia, nuclear pleomorphism, or aberrant mitoses. Immunohistochemical (IHC) staining disclosed focal, weak keratin positivity in two lesions, whereas vimentin (diffuse, strongly positive) and SMA (tram‐track pattern) were present in each instance, and ALK (D5F3) was entirely negative. FISH analysis confirmed USP6 gene rearrangements in all seven cases, showing no ALK gene rearrangements. RNA sequencing results showed an MYH9::USP6 gene fusion in only one lesion (No. 6). Conclusion: A subset of PSCN is marked by USP6 gene rearrangements, a genetic feature of nodular fasciitis (NF). Given its similarity to NF, a designation as USP6‐associated neoplasm (UAN) seems reasonable, signifying a transient clonal neoplastic lesion. [ABSTRACT FROM AUTHOR]