Affiliation:
1. Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis Indiana USA
2. Department of Pathology The University of Texas MD Anderson Cancer Center Houston Texas USA
3. Bone Tumour Reference Center, Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
4. Department of Pathology Dartmouth‐Hitchcock Medical Center Lebanon New Hampshire USA
Abstract
AbstractExtraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain differentiation predominantly arising in deep soft tissue. Its conventional morphologic appearance manifests as a relatively well‐circumscribed, multilobular tumor composed of uniform short spindle‐to‐ovoid primitive mesenchymal cells with deeply eosinophilic cytoplasm arranged in anastomosing cords within abundant myxoid matrix. The genetic hallmark of EMC has long been considered to be pathognomonic gene rearrangements involving NR4A3, which when fused to TAF15, often have high‐grade morphology with increased cellularity, moderate to severe cytologic atypia, and rhabdoid cytomorphology. Herein, we describe two cases of EMC with TAF15::NR4A3 fusion that appear morphologically distinct from both conventional and high‐grade EMC. Both cases had an unusual biphasic appearance and showed diffuse positivity for p63, mimicking myoepithelial tumors. DNA methylation profiling demonstrated that both cases clearly cluster with EMC, indicating that they most likely represent morphologically distinct variants of EMC. The clinical significance and prognostic impact of this morphologic variance remains to be determined. Molecular testing, including DNA methylation profiling, can help to confirm the diagnosis and avoid confusion with mimics; it adds another layer of data to support expanding the morphologic spectrum of EMC.