Novel CRTC1::MRTFB(MKL2) Gene Fusion detected in Myxoid Mesenchymal Neoplasms with Myogenic Differentiation involving Bone and Soft Tissue

Laura M Warmke; Christopher D Collier; Paul J Niziolek; Jessica L Davis; Ying S Zou; Michael Michal; Robert C Bell; Maria Luisa C Policarpio-Nicolas; Yu-Wei Cheng; Lauren Duckworth; Josephine K Dermawan; Karen J Fritchie; Carina A Dehner

doi:10.1016/j.modpat.2024.100518

Novel CRTC1::MRTFB(MKL2) Gene Fusion detected in Myxoid Mesenchymal Neoplasms with Myogenic Differentiation involving Bone and Soft Tissue

Mod Pathol. 2024 May 17:100518. doi: 10.1016/j.modpat.2024.100518. Online ahead of print.

Affiliations

¹ Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
² Department of Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Radiology and Imaging Sciences, Musculoskeletal Imaging, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
⁵ Biopticka Laboratory, Ltd, Plzen, Czech Republic.
⁶ Department of Pathology, Michigan University, Ann Arbor, MI, USA.
⁷ Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
⁸ Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: cadehner@iu.edu.

PMID: 38763420
DOI: 10.1016/j.modpat.2024.100518

Abstract

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present three cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 2 female and 1 male patient with a median age of 72 (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). While one tumor presented as an incidental finding, the other two tumors were noted given their persistent growth. At the time of last follow-up, one patient was alive with unresected disease at 6 months, one patient was alive without evidence of disease at 12 months after surgery and one patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

Keywords: CRTC1; MRTFB(MKL2); bone; mesenchymal tumor; myogenic; myxoid; soft tissue.