TY  - JOUR
AU  - Rizwan, Raheel
AU  - Venkataramani, Vivek
AU  - Haug, Lukas
AU  - Hattery, Travis
AU  - Chen, Mark
AU  - Nakitandwe, Joy
AU  - Shurtleff, Sheila
AU  - Azzato, Elizabeth M
AU  - Teleanu, Maria-Veronica
AU  - Hüllein, Jennifer
AU  - Fröhling, Stefan
AU  - Stoehr, Robert
AU  - Billings, Steven D
AU  - Michal, Michael
AU  - Fritchie, Karen J
AU  - Agaimy, Abbas
AU  - Dermawan, Josephine K
TI  - ZFTA::NCOA1/2-rearranged Epithelioid Mesenchymal Tumor-A Phenotypically Distinct Myoepithelial-like Neoplasm Epigenetically Overlapping with Chondroid Lipoma.
JO  - Modern pathology
VL  - 39
IS  - 1
SN  - 0893-3952
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2025-02590
SP  - 100939
PY  - 2026
N1  - Volume 39, Issue 1, January 2026, 100939
AB  - ZFTA (formerly C11orf95) gene rearrangements are recurrent in rare tumors of the central nervous system, such as ependymomas (mostly ZFTA::RELA), and soft tissue tumors such as chondroid lipomas (ZFTA::MRTFB). To date, among mesenchymal tumors, the fusion ZFTA::NCOA1 has only been reported in a single case of chondroid lipoma. We describe five distinct soft tissue tumors harboring ZFTA::NCOA1/2 fusions. The tumors arose from 2 female and 3 males with a median age of 31 years (range 30-72 years). All tumors were well-circumscribed involving the deep (4 cases) or superficial (1 case) soft tissue of the proximal limbs with a median greatest dimension of 4.2 cm (range 1.7-6.0 cm). Histologically, they displayed lobulated architecture and were composed of monotonous epithelioid to plasmacytoid cells arranged in cords, chains and nests within myxohyaline or sclerosed stroma. Focal loose myxoid reticulate areas and prominent dilated and hyalinized blood vessels were present. One tumor showed focal spindle cells, while another demonstrated necrosis and atypical mitotic figures. Definitive adipocytic, lipoblastic, or clear-cell features were absent except in one case. Immunohistochemistry was nonspecific without any consistent lineage-defining marker expression. Targeted RNA sequencing confirmed ZFTA::NCOA1 fusions in 3 and ZFTA::NCOA2 fusion in 2 cases. DNA methylation profiling, available in 4 cases, demonstrated a shared epigenetic profile with chondroid lipoma but not other tumors with histologic or genetic overlap. Copy number variation analysis showed a flat copy number profile in 3 cases and chr9p arm-level copy number loss in the case with necrosis and mitotic activity. All patients underwent complete excision; no recurrences or metastases were observed over a limited follow-up period (available in 4 cases, range 8-24 months, median 10.5 months). In conclusion, ZFTA::NCOA1/2-rearranged epithelioid mesenchymal tumors represent a novel, morphologically distinct entity, genetically and epigenetically overlapping with chondroid lipoma. Expanded cohorts and long-term follow-up are necessary to clarify their precise classification and biologic behavior.
KW  - NCOA1 (Other)
KW  - NCOA2 (Other)
KW  - ZFTA (Other)
KW  - methylation profiling (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41270902
DO  - DOI:10.1016/j.modpat.2025.100939
UR  - https://inrepo02.dkfz.de/record/306525
ER  -