Department of Pathology of West China Hospital, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Histopathology. 2024 Dec;85(6):868-878. doi: 10.1111/his.15245. Epub 2024 Jun 20.
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.
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.
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.
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.
核蛋白睾丸（NUT）癌（NC）是一种罕见且高度侵袭性的肿瘤，其特征在于核蛋白睾丸家族成员 1（NUTM1）基因的染色体重排，也称为 NUT 基因。NC 主要发生在头颈部、纵隔和肺部。一般来说，口腔原发 NC 极为罕见，且报道较少。
收集了来自 10 家医院的 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 蛋白免疫组化染色，并对 NUT IHC 阳性病例进一步进行荧光原位杂交（FISH）和 RNA 测序检测。
在五例（111 例中的 5 例，4.5%）肿瘤细胞中检测到 NUT 蛋白的表达。这些病例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 例患者存在 BRD4::NUT 重排，2 例患者存在非 BRD4::NUT 重排模式。RNA 测序结果证实了两例 BRD4::NUT 重排。
据我们所知，这是口腔 NC 的第一项也是最大规模的回顾性研究，我们发现 NC 容易被误诊为低分化口腔鳞状细胞癌（SCC）或低分化癌。4 例 NC 病例的形态和免疫表型与 SCC 相似，其中 3 例可见突然角化。因此，在这些形态的口腔恶性肿瘤中，有必要检测 NUT 蛋白以筛查 NC，尤其是对于更有可能被误诊为其他类型癌症的年轻患者。
