Kantonsspital St.Gallen

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

abstract 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.
citation 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;.
type journal paper/review (English)
date of publishing 13-03-2021
journal title Mod Pathol
ISSN electronic 1530-0285
PubMed 33714983
DOI 10.1038/s41379-021-00792-z