DOI: 10.1177/17588359261490610 ISSN: 1758-8359
Clinicopathologic and molecular features of head and neck NUT carcinoma: Analysis of 25 cases, including 5 with adenoid differentiation
Yunyun Yang, Yue Hao, Chunwei Xu, Yahui Li, Xiaochen Li, Honggang Liu, Yingshi Piao
Background
Nuclear protein in testis (NUT) carcinoma is a highly aggressive malignancy driven by
NUTM1
gene fusions, with a median overall survival of 6.5–10.6 months. A comprehensive summary of the morphological and molecular features of head and neck NUT carcinoma is lacking, resulting in inconsistencies in diagnosis and treatment.
Objective
To characterize the pathological and molecular features of primary head and neck NUT carcinoma and explore optimal management strategies.
Design
This study was a single-center retrospective analysis.
Methods
Fluorescence in situ hybridization was used to detect
NUTM1
gene rearrangements. RNA sequencing was performed to analyze the genomic and immune landscapes. Overall survival (OS) was evaluated in relation to patient characteristics and treatment modalities.
Results
This study included 25 patients with NUT carcinoma. Adenoid differentiation was observed in 5 cases (2
NSD3
fusions, 1
BRD3
fusion, and 2
BRD4
fusions). Neuroendocrine differentiation was identified in 9 cases (36%). The most common
NUT
fusion partner was
BRD4
(86%), followed by
NSD3
(9%) and
BRD3
(5%). Tumors with adenoid differentiation showed significant upregulation of
COL4A5
,
H2AFY2
, and
FLJ00104
and significantly reduced M2 macrophage infiltration (P < 0.05). Compared with the
BRD3/BRD4
fusion group, the
NSD3
fusion group exhibited 407 downregulated and 14 upregulated genes (FDR < 0.05). Tumors with
BRD3/BRD4
fusions had a significantly lower proportion of resting CD4
+
memory T cells than those with
NSD3
fusions (P < 0.05). The neuroendocrine-positive subgroup showed significant overexpression of
PHF21B
(P = 0.025). Follow-up data indicated that early radiotherapy significantly reduced mortality (P = 0.017). Patients with neuroendocrine differentiation had significantly higher mortality than those without (P = 0.019).
Conclusion
Patients with NUT with adenoid differentiation or different gene fusions exhibit distinct gene expression profiles and immune landscapes. Neuroendocrine differentiation is associated with poor prognosis. Radiotherapy may be associated with favourable outcomes and warrants further investigation.