Institute of Pathology, University Hospital, Erlangen, Germany.
Instituto de Anatomia Patológica, Faculdade de Medicina, Universidade de Lisboa.
Am J Surg Pathol. 2018 Jul;42(7):877-884. doi: 10.1097/PAS.0000000000001046.
NUT carcinoma (NC) represents a rare subset of highly aggressive poorly differentiated carcinomas characterized by rearrangement of the NUT (aka NUTM1, nuclear protein in testis) gene, most commonly fused to BRD4. Originally described as a mediastinal/thymic malignancy, NC has been reported at a variety of anatomic regions including the upper and lower aerodigestive tract. To date, only 7 NC cases of probable salivary gland origin have been reported. We herein describe 3 new cases (all affecting the parotid gland) in 2 women (39- and 55-y old) and 1 man (35-y old). Histologic examination showed poorly differentiated neoplasms composed of poorly cohesive small-sized to medium-sized cells with variable squamoid cell component that was focal and abrupt. Immunohistochemistry showed uniform expression of p63 and distinctive punctate expression of the NUT antigen in the tumor cell nuclei. Review of the reported salivary gland NC cases (total, 10) showed a male:female ratio of 1.5:1 and an age range of 12 to 55 years (median, 29 y). Site of the primary tumor was the parotid (7), sublingual (2), and submandibular (1) glands. All presented as rapidly growing masses treated by surgery followed by adjuvant radiotherapy/chemotherapy. Initial nodal status was positive in 8/10. At last follow-up (1 to 24 mo; median, 5 mo), 7/10 patients died of disease at a median of 5.5 months (1 to 24 mo) and only 2 were disease free at 7 and 14 months. Of 9 cases with genetic data, the fusion partner was BRD4 (n=7), non-BRD4/3 (n=1), or undetermined (n=1). None of 306 carcinomas spanning the spectrum of salivary carcinoma types screened by NUT immunohistochemistry was positive. This is the first small series on salivary NC highlighting the importance to include this rare disease in the differential diagnosis of poorly differentiated salivary gland carcinomas and in cases of presumable poorly differentiated carcinoma of unknown origin.
NUT 癌（NC）是一种罕见的高度侵袭性低分化癌，其特征是 NUT（又名 NUTM1，睾丸核蛋白）基因重排，最常见的融合伴侣是 BRD4。最初描述为纵隔/胸腺恶性肿瘤，已在多种解剖部位报道，包括上、下呼吸道。迄今为止，仅报道了 7 例可能来源于唾液腺的 NC 病例。本文描述了 3 例新病例（均累及腮腺），2 例为女性（39 岁和 55 岁），1 例为男性（35 岁）。组织学检查显示为低分化肿瘤，由大小不一、黏附性差的小至中等大小细胞组成，具有局灶性和突然出现的鳞状细胞成分。免疫组化显示 p63 均匀表达，肿瘤细胞核中 NUT 抗原呈独特的点状表达。对报道的唾液腺 NC 病例（共 10 例）进行回顾性分析显示，男女比例为 1.5:1，年龄范围为 12 至 55 岁（中位数 29 岁）。原发肿瘤部位为腮腺（7 例）、舌下腺（2 例）和下颌下腺（1 例）。所有病例均表现为生长迅速的肿块，经手术治疗后辅以辅助放疗/化疗。10 例中初始淋巴结状态阳性 8 例。末次随访（1 至 24 个月；中位数 5 个月）时，7 例患者因疾病死亡，中位时间为 5.5 个月（1 至 24 个月），仅 2 例患者无疾病生存，分别为 7 个月和 14 个月。在有基因数据的 9 例中，融合伴侣为 BRD4（n=7）、非 BRD4/3（n=1）或未确定（n=1）。在经 NUT 免疫组化筛查的涵盖各种唾液腺癌类型的 306 例癌中，均未见阳性。这是关于唾液腺 NC 的首个小系列研究，强调了在低分化唾液腺癌和可能来源不明的低分化癌的鉴别诊断中纳入这种罕见疾病的重要性。
