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Tumor Discovery Expert consensus of NUT carcinoma

diffuse bone infiltration and express CD34, which can lead high IHC specificity, molecular testing can identify
to misdiagnosis as acute leukemia or other hematologic various fusion partners of NUTM1, which helps predict
diseases. NUT carcinoma lacks specific diagnostic patient prognosis. BET inhibitors may have suboptimal
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morphological features; it is a poorly differentiated or efficacy for patients with gene fusions not dependent on
undifferentiated tumor, with some cases exhibiting sudden BRD4. Therefore, identifying NUTM1 fusion partners
keratinized foci, leukocyte infiltration, and extensive and available drug targets through second-generation
necrosis. At present, NUTM1 rearrangement can be sequencing can validate the pathological diagnosis,
confirmed using IHC staining for NUT positivity or predict disease prognosis, and inform treatment options,
FISH (with over 20% of tumor cells showing the t(15;19) including later-stage drug therapies and combination
(q14;p13.1) separation probe-positive), along with other treatments. 41,62
molecular techniques such as cell cytogenetics, reverse
transcription polymerase chain reaction, and second- 4.7.1. Recommendation 3
generation sequencing, all of which assist in diagnosing The clinical presentation, histopathology, and conventional
NUT carcinoma. In the 2021 edition of the WHO IHC features of NUT carcinoma lack specificity,
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classification of lung cancer, NUT carcinoma is categorized highlighting the importance of using specific NUT
under “other epithelial tumors of the lung.” antibodies for IHC staining in its diagnosis. For patients
The 2024 National Comprehensive Cancer Network with an initial diagnosis accompanied by rapid progression
clinical practice guidelines for non-small-cell lung or distant metastasis, especially those with poorly
cancer recommend testing for NUT rearrangement in differentiated carcinomas or small round cell tumors, it is
all poorly differentiated lung cancers that lack glandular strongly recommended to consider NUT IHC examination
differentiation or specific causes, especially in nonsmokers (evidence level: grade 4; recommendation level: strong
or young patients. However, this recommendation is not recommendation). In addition, FISH or high-throughput
widely followed due to the rarity of NUT carcinoma. sequencing should be considered to identify the type of
Moreover, when NUT carcinoma masses are detected NUTM1 fusion partner (such as BRD4, BRD3, and NSD3)
in non-midline anatomical structures (e.g., head/neck/ (evidence level: grade 5; recommendation level: strong
thorax) or in elderly patients with limited tumor samples recommendation).
that lack typical NUT carcinoma morphology, NUT IHC 4.8. Treatment
staining may not be performed, potentially leading to
misdiagnosis. According to the 2023 Chinese Society of Given the highly invasive nature and poor prognosis of
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Clinical Oncology guidelines for head-and-neck tumors, NUT carcinoma, it is essential to emphasize the importance
NUT IHC testing is recommended as a level II diagnostic of multidisciplinary team (MDT) consultations, including
tool. It is advised for patients with poorly differentiated the involvement of a Molecular Tumor Board (MTB). In
carcinoma, regardless of age or medical history. According the MTB, experts from various disciplines collaboratively
to the WHO recommendations, NUT antibody IHC analyzed the patients’ clinical manifestations, imaging,
staining with a cutoff value of ≥50% positivity for the pathology, and molecular biology/genetic data to
C52B1 clone has 100% specificity and 87% sensitivity for comprehensively assess the patient’s general condition,
diagnosing NUT carcinoma. Although transcriptome disease diagnosis, extent of invasion, and prognosis.
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sequencing has higher sensitivity in NGS than DNA-based Based on existing treatment standards and evidence-based
NGS, false negatives are still possible. Therefore, NGS medicine, combined with available treatment methods,
results should be validated using other molecular detection treatment plans should be adjusted in real time according
methods to ensure diagnostic accuracy. to changes in the patient’s condition to develop the most
appropriate treatment strategy.
Fluorescence in situ hybridization with a NUTM1
breakpoint 15q14 probe is considered one of the essential NUT carcinoma can occur in various organs, and
methods for diagnosing NUT carcinoma. However, FISH currently, there is no specific staging system exists for this
2
has low resolution and may miss potential breakpoints. cancer. Therefore, the staging system from the American
Therefore, when cases are IHC NUT-positive, full-length Joint Committee on Cancer for tumors in corresponding
NUTM1 probe FISH or second-generation sequencing locations may be applied to NUT carcinoma.
(preferably transcriptome sequencing) is recommended to A study of 124 patients with NUT carcinoma showed
confirm the diagnosis. 2 an objective remission rate of 49% for treatments
At present, NUT carcinoma can be diagnosed using involving surgery, radiotherapy, and chemotherapy.
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NUTM1 IHC or FISH. While NUT carcinoma shows New treatment possibilities may emerge from targeting

Volume 3 Issue 4 (2024) 16 doi: 10.36922/td.4904