TY - JOUR
T1 - NUTM1 -rearranged Carcinoma of the Thyroid
T2 - A Distinct Subset of NUT Carcinoma Characterized by Frequent NSD3 - NUTM1 Fusions
AU - Barletta, Justine A.
AU - Gilday, Steven D.
AU - Afkhami, Michelle
AU - Bell, Diana
AU - Bocklage, Theresa
AU - Boisselier, Pierre
AU - Chau, Nicole G.
AU - Cipriani, Nicole A.
AU - Costes-Martineau, Valerie
AU - Ghossein, Ronald A.
AU - Hertzler, Hans J.
AU - Kramer, Alan M.
AU - Limaye, Sewanti
AU - Lopez, Carlos A.
AU - Ng, Tony L.
AU - Weissferdt, Annikka
AU - Xu, Bin
AU - Zhang, Songlin
AU - French, Christopher A.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - NSD3-NUTM1
KW - NUT carcinoma
KW - NUTM1
KW - thyroid
UR - http://www.scopus.com/inward/record.url?scp=85140967035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140967035&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001967
DO - 10.1097/PAS.0000000000001967
M3 - Article
C2 - 36040068
AN - SCOPUS:85140967035
SN - 0147-5185
VL - 46
SP - 1706
EP - 1715
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 12
ER -