Abstract：
OBJECTIVE: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically.
METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases.
RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases.
CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.
METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases.
RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases.
CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.
摘要：
目的：核蛋白睾丸（NUT）癌（NC）是一种罕见且高度侵袭性的肿瘤，其特征是核蛋白睾丸家族成员1（NUTM1）基因的染色体重排，也被称为NUT基因。NC主要发生在头颈部,纵隔和肺。总的来说,口腔中的原发性NC极为罕见，偶尔有报道。
方法：从10家医院收集了111例福尔马林固定和石蜡包埋的低分化口腔和口咽肿瘤标本。对这些样本进行NUT蛋白IHC染色，并对NUTIHC阳性病例进一步进行荧光原位杂交(FISH)和RNA测序检测。
结果：5例（111例中5例，4.5％）肿瘤细胞中NUT蛋白的表达。这些病例中的肿瘤位于口腔底部，唇,舌根,牙龈和硬腭。FISH检测结果显示3例患者为BRD4::NUT重排，2例患者为非BRD4::NUT重排模式。RNA测序成果证实BRD4：：NUT重排两例。
结论：据我们所知，这是第一个也是最大的口腔NC回顾性研究，我们发现NC容易误诊为低分化口腔鳞状细胞癌（SCC）或低分化癌。4例NC与SCC形态及免疫表型相似,在3例中观察到突然的角质化。因此,在具有这些形态的口腔恶性肿瘤中，有必要检测NUT蛋白用于NC筛查，特别是对于更容易被误诊为其他类型癌症的年轻患者。
方法：从10家医院收集了111例福尔马林固定和石蜡包埋的低分化口腔和口咽肿瘤标本。对这些样本进行NUT蛋白IHC染色，并对NUTIHC阳性病例进一步进行荧光原位杂交(FISH)和RNA测序检测。
结果：5例（111例中5例，4.5％）肿瘤细胞中NUT蛋白的表达。这些病例中的肿瘤位于口腔底部，唇,舌根,牙龈和硬腭。FISH检测结果显示3例患者为BRD4::NUT重排，2例患者为非BRD4::NUT重排模式。RNA测序成果证实BRD4：：NUT重排两例。
结论：据我们所知，这是第一个也是最大的口腔NC回顾性研究，我们发现NC容易误诊为低分化口腔鳞状细胞癌（SCC）或低分化癌。4例NC与SCC形态及免疫表型相似,在3例中观察到突然的角质化。因此,在具有这些形态的口腔恶性肿瘤中，有必要检测NUT蛋白用于NC筛查，特别是对于更容易被误诊为其他类型癌症的年轻患者。
