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@ARTICLE{Rizwan:306525,
author = {R. Rizwan and V. Venkataramani and L. Haug and T. Hattery
and M. Chen and J. Nakitandwe and S. Shurtleff and E. M.
Azzato and M.-V. Teleanu$^*$ and J. Hüllein$^*$ and S.
Fröhling$^*$ and R. Stoehr and S. D. Billings and M. Michal
and K. J. Fritchie and A. Agaimy and J. K. Dermawan},
title = {{ZFTA}::{NCOA}1/2-rearranged {E}pithelioid {M}esenchymal
{T}umor-{A} {P}henotypically {D}istinct {M}yoepithelial-like
{N}eoplasm {E}pigenetically {O}verlapping with {C}hondroid
{L}ipoma.},
journal = {Modern pathology},
volume = {39},
number = {1},
issn = {0893-3952},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2025-02590},
pages = {100939},
year = {2026},
note = {Volume 39, Issue 1, January 2026, 100939},
abstract = {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.},
keywords = {NCOA1 (Other) / NCOA2 (Other) / ZFTA (Other) / methylation
profiling (Other)},
cin = {B340},
ddc = {610},
cid = {I:(DE-He78)B340-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41270902},
doi = {10.1016/j.modpat.2025.100939},
url = {https://inrepo02.dkfz.de/record/306525},
}