NUTM1-rearranged colorectal sarcoma: a clinicopathologically and genetically distinctive malignant neoplasm with a poor prognosis
Benjamin J Van Treeck, Judith Jebastin Thangaiah, Jorge Torres-Mora, Todd M Stevens, Christian Rothermundt, Matteo Fassan, Fotios Loupakis, Joachim Diebold, Jason L Hornick, Kevin C Halling & Andrew L Folpe
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abstract
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NUTM1 gene rearrangements were originally identified in NUT
carcinoma. Recently, NUTM1 has been discovered to rearrange with a
variety of gene partners in malignancies of diverse location and
type. Only one NUTM1-rearranged tumor occurring in the colon has
been reported. Herein we report five such tumors. The five tumors
occurred in four females and one male, ranging from 38 to 67 years
of age (median 51 years). The masses occurred in the colon (cecum,
descending, sigmoid) and ileocecal valve region, measuring
2.5-20 cm in size (median 7 cm). Four patients had
metastases at presentation (liver, n = 4; lymph nodes,
n = 3). Histologically, the lesions arose in the
submucosa, infiltrating into the mucosa and muscularis propria, and
grew in fibrosarcoma-like fascicles and sheets of epithelioid or
rhabdoid cells, with foci of hyalinized to vaguely osteoid-like
matrix. The tumors were composed of relatively monomorphic, spindled
to epithelioid cells with focal rhabdoid morphology, hyperchromatic
nuclei, and small nucleoli. Mitotic activity was usually low (range
1-14/10 HPF; median 5/10 HPF); necrosis was present in two cases.
Variable keratin expression and uniform nuclear NUT expression was
present; KIT/DOG1 were negative and SMARCB1/SMARCA4 were retained.
Next-generation sequencing identified MXD4-NUTM1 rearrangement in
all cases (breakpoints: MXD4 exon 5, NUTM1 exons 2 or 3). Follow-up
showed one of the four patients who presented with metastases to be
dead of disease at 30 months; the other three patients were alive
with metastatic disease. The final patient is disease-free, 5 months
after diagnosis. NUTM1-rearranged colorectal sarcomas have
characteristic morphologic, immunohistochemical, and molecular
genetic features, suggesting that they represent a distinct entity
within the family of NUTM1-rearranged neoplasia. A NUTM1-rearranged
tumor should be considered for any difficult-to-classify submucosal
spindle cell neoplasm of the gastrointestinal tract, in particular
keratin-positive tumors showing an unusual combination of
fibrosarcomatous, epithelioid to rhabdoid and hyalinized
morphologies. Recognition of MXD4-NUTM1 rearranged sarcomas may be
therapeutically important, even though best treatment is currently
elusive/unknown.
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citation
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Van Treeck B J, Thangaiah J J, Torres-Mora J, Stevens T M,
Rothermundt C, Fassan M, Loupakis F, Diebold J, Hornick J L, Halling
K C, Folpe A L. NUTM1-rearranged colorectal sarcoma: a
clinicopathologically and genetically distinctive malignant neoplasm
with a poor prognosis. Mod Pathol 2021;.
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type
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journal paper/review (English)
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date of publishing
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13-03-2021
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journal title
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Mod Pathol
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ISSN electronic
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1530-0285
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PubMed
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33714983
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DOI
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10.1038/s41379-021-00792-z
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