NUTM1 -rearranged carcinoma of the thyroid: A distinct subset of NUT carcinoma characterized by frequent NSD3 - NUTM1 fusions Journal Article
| Authors: | Barletta, J. A.; Gilday, S. D.; Afkhami, M.; Bell, D.; Bocklage, T.; Boisselier, P.; Chau, N. G.; Cipriani, N. A.; Costes-Martineau, V.; Ghossein, R. A.; Hertzler, H. J.; Kramer, A. M.; Limaye, S.; Lopez, C. A.; Ng, T. L.; Weissferdt, A.; Xu, B.; Zhang, S.; French, C. A. |
| Article Title: | NUTM1 -rearranged carcinoma of the thyroid: A distinct subset of NUT carcinoma characterized by frequent NSD3 - NUTM1 fusions |
| Abstract: | NUT carcinoma (NC) is a rare subtype of squamous cell carcinoma defined by NUTM1 rearrangements encoding NUT fusion oncoproteins (the most frequent fusion partner being BRD4 ) that carries a very poor prognosis, with most patients dying in under 1 year. Only rare primary thyroid NCs have been reported. Here, we evaluated a series of 14 cases. The median patient age at diagnosis was 38 years (range: 17 to 72 y). Eight of 13 cases with slides available for review (62%) showed a morphology typical of NC, whereas 5 (38%) had a non-NC-like morphology, some of which had areas of cribriform or fused follicular architecture resembling a follicular cell-derived thyroid carcinoma. For cases with immunohistochemistry results, 85% (11/13) were positive for NUT on biopsy or resection, though staining was significantly decreased on resection specimens due to fixation; 55% (6/11) were positive for PAX8, and 54% (7/13) for TTF-1. Tumors with a non-NC-like morphology were all positive for PAX8 and TTF-1. The fusion partner was known in 12 cases: 9 (75%) cases had a NSD3-NUTM1 fusion, and 3 (25%) had a BRD4-NUTM1 fusion. For our cohort, the 2-year overall survival (OS) was 69%, and the 5-year OS was 58%. Patients with NC-like tumors had a significantly worse OS compared with that of patients with tumors with a non-NC-like morphology ( P =0.0462). Our study shows that NC of the thyroid can mimic other thyroid primaries, has a high rate of NSD3 - NUTM1 fusions, and an overall more protracted clinical course compared with nonthyroid primary NC. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | adolescent; adult; aged; middle aged; young adult; oncoprotein; genetics; squamous cell carcinoma; carcinoma, squamous cell; cell cycle protein; cell cycle proteins; nuclear protein; transcription factor; transcription factors; nuclear proteins; oncogene proteins, fusion; thyroid gland; humans; human; brd4 protein, human |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 46 |
| Issue: | 12 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2022-12-01 |
| Start Page: | 1706 |
| End Page: | 1715 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000001967 |
| PUBMED: | 36040068 |
| PROVIDER: | scopus |
| PMCID: | PMC9669222 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work