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Tumor Discovery Expert consensus of NUT carcinoma

and hemorrhage (13.25%, 11/83), resulting from local patterns accompanied by extensive necrosis. Regarding
tumor compression and invasion of surrounding tissues. specific differentiation, 25% of cases demonstrated
neuroendocrine differentiation, 15% exhibited
3.2. Tumor characteristics myoepithelial features, and 60% showed no specific

Tumor diameter: The average tumor diameter of NUT differentiation. Many cases presented with numerous
carcinoma patients was 6.04 cm. The average diameter in mitotic figures and were often associated with geographic
thoracic NUT carcinoma (6.86 cm) was larger than that of necrosis. The stromal component varies from minimal to
head-and-neck NUT carcinoma (4.08 cm). fibrotic, with occasional infiltration of inflammatory cells.
The most prevalent IHC findings for NUT carcinoma
3.2.1. NUT carcinoma fusion partners included tumor protein p63 (43.84%, 153/349),
Among patients with known specific NUTM1 cytokeratin AE1/AE3 (26.65%, 93/349), ribonucleic acid-
fusion partners, bromodomain-containing protein 4 binding protein p40 (24.36%, 85/349), and cytokeratin
(BRD4)::NUTM1 was the most common (56.4%, 167/296), 5/6 (CK5/6; 22.92%, 80/349). The average Ki-67 index
followed by nuclear receptor binding SET domain protein expression was approximately 55.16% (15 – 95%).
3 (NSD3)::NUTM1 (9.80%, 29/296), and bromodomain-
containing protein 3 (BRD3)::NUTM1 (6.76%, 20/296). 3.3. Treatment strategy
We identified 17 primary treatment modalities for current
3.2.2. NUT carcinoma metastasis NUT carcinoma patients based on the patient’s previous
A total of 29 metastatic sites were identified. About 52.28% treatment histories. NUT carcinoma is generally insensitive
(275/526) of all patients had distant metastasis. Among to chemotherapy and radiotherapy. 1,18,28 Evidence suggests
thoracic NUT carcinoma patients, 60.25% (144/239) had that surgery, BET inhibitors, HDAC inhibitors, and
distant metastasis, while 40.85% (67/164) of head-and- immunotherapy may be potentially effective against
neck NUT carcinoma patients had distant metastasis. NUT carcinoma. 1,18,28 However, the sample sizes for BET
These findings suggest that thoracic NUT carcinoma may inhibitors, HDAC inhibitors, and immunotherapy are
be more prone to distant metastasis than head-and-neck generally limited. When combined with chemotherapy
NUT carcinoma. Based on the available data, the bones and radiotherapy, the sample size for each group was
were the most common site of distant metastasis (37.09%, insufficient (<10 patients). Therefore, we grouped
102/275). The likelihood of bone metastasis in thoracic patients who received surgery, BET inhibitors, HDAC
NUT carcinoma patients (48.61%, 70/144) was higher inhibitors, and immunotherapy into a category labeled
than in head-and-neck NUT carcinoma patients (35.82%, “include surgery/BET/immunotherapy.” For example,
24/67). In addition, NUT carcinoma, found in both patients treated with BET inhibitors in combination with
thoracic and head/neck regions, was prone to metastasize chemotherapy or radiotherapy were collectively assigned
to the liver (13.45%, 37/275). to the “include BET” group.

3.2.3. NUT carcinoma histopathology and 3.3.1. Current treatment modalities
immunohistochemistry Approximately 59.32% (312/526) of patients have relatively
Based on our comprehensive analysis of the available comprehensive treatment data. Among the various
literature, the histopathology of NUT carcinoma therapeutic approaches, patients received chemotherapy
predominantly demonstrates poor differentiation (18.59%, 58/312), chemotherapy combined with
(81.90%) and undifferentiation (3.02%). Notably, 72 radiotherapy (11.54%, 36/312), chemotherapy combined
studies reported partial or focal squamous differentiation, with surgery and radiotherapy (9.94%, 31/312), and
while 32 studies indicated the absence of squamous surgery combined with immunotherapy (9.62%, 30/312).
differentiation. The remaining studies did not specifically In thoracic NUT carcinoma patients, chemotherapy
address this aspect. Among the literature reporting (28.28%, 41/145) and chemotherapy combined with
tumor cell morphology of NUT carcinoma, tumor cells radiotherapy (14.48%, 21/145) were the most common
primarily present with three morphological patterns: approaches, with 10.34% (30/312) of patients receiving
round cell morphology (approximately 40%), spindle chemotherapy combined with surgery. Conversely, head-
cell features (30%), and epithelioid characteristics and-neck NUT carcinoma patients more commonly
(30%). The cells typically exhibit monomorphic growth received treatment plans based on surgery, including
patterns characterized by vesicular nuclei, prominent chemotherapy/radiotherapy/surgery (20.34%, 24/118),
nucleoli, and varying amounts of cytoplasm. Microscopic radiotherapy/surgery (19.49%, 23/118), and surgery
examination frequently reveals sheet-like growth combined with immunotherapy (16.95%, 20/118).

Volume 3 Issue 4 (2024) 8 doi: 10.36922/td.4904