ArticleThe Journal of pathology2025
Soft tissue sarcoma with MN1 gene fusions: a report of three cases with aggressive clinical behavior.
Article in The Journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Molecularly Variant Synovial Sarcoma of the Lower Lip: MN1::SSX1 Fusion as a Diagnostic Pitfall in the Head and Neck.Head and neck pathology · 2026Article
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6 authors.
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Abstract
Canonical MN1 fusions with either BEND2 or CXXC5 gene partners represent the molecular hallmark of astroblastoma, a stand-alone group among central nervous system (CNS) high-grade neuroepithelial tumors based on their distinct methylation profile. Outside the CNS, MN1 fusions have been rarely reported, mostly with nonrecurrent gene partners. Herein, we present three cases of soft tissue sarcomas harboring MN1 gene rearrangements, two of which had MN1 (exon 1)::CXXC5 (exon 2) gene fusion and the last had MN1 (exon 1)::ZFP64 (exon 2) gene fusion. The tumors occurred in young to middle-aged adults (two females and one male) and involved the preauricular, abdominal, and sacral soft tissue. Patients with MN1::CXXC5 fusion had widespread metastatic disease at presentation. Histologically, tumors with the MN1::CXXC5 fusion showed nests of monomorphic round and focally spindled cells, compatible with round cell sarcoma, while MN1::ZNFP64 fused tumors exhibited monomorphic spindle cells arranged in storiform and short fascicular patterns. Mitotic activity was brisk in all cases; however, tumor necrosis was minimal to absent. MN1::CXXC5 fused tumors exhibited CD99 and S100 expression, an immunophenotype that is not specific for a particular line of differentiation and is distinct from astroblastoma. MN1::ZNFP64 were positive for p63 and androgen receptor (AR) expression. Low tumor mutation burden and low levels of genome alteration were seen in all cases. DNA methylation profiling showed that the three cases could not be classified into any of the current methylation classes using the DKFZ classifier for sarcomas (version 12.2) or CNS tumors (version 12.8). T-distributed Stochastic Neighbor Embedding analysis revealed that the three sarcomas with MN1 gene rearrangement clustered together, forming a distinct group, in close proximity to epithelioid sarcoma, separate from CNS high-grade neuroepithelial tumor with MN1 alterations. In our series, all three cases exhibited aggressive clinical behavior; notably, the two patients with MN1::CXXC5 gene fusion sarcomas succumbed to the disease within 20 to 23 months. © 2025 The Pathological Society of Great Britain and Ireland.
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