Suzuki Shioto, Kurabe Nobuya, Minato Hiroshi, Ohkubo Aki, Ohnishi Ippei, Tanioka Fumihiko, Sugimura Haruhiko
Division of Pathology, Iwata City Hospital, Japan.
Department of Tumor Pathology, Hamamatsu University School of Medicine, Japan.
Pathol Res Pract. 2014 Jun;210(6):383-8. doi: 10.1016/j.prp.2014.01.013. Epub 2014 Feb 22.
NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases.
An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy.
We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity.
睾丸核蛋白（NUT）中线癌（NMC）是一种最近被描述的侵袭性恶性肿瘤，其遗传学特征为15q14处NUT基因座重排。在大约三分之二的病例中，特征性的t(15;19)导致融合癌基因BRD4-NUT。仅有10例鼻窦NMC的病例报道，其中无日本患者。
一名18岁女性因鼻腔肿瘤迅速进展入院。活检显示为未分化肿瘤，无鳞状分化。肿瘤细胞具有圆形至椭圆形核，核染色质呈泡状，核仁明显，细胞质稀少。免疫组化染色显示波形蛋白和NUT呈强阳性，局灶性CD138阳性，仅EMA和细胞角蛋白AE1/AE3呈散在斑点状染色。细胞遗传学和荧光原位杂交分析显示t(15;19)和BRD4-NUT基因重排。直接测序鉴定出BRD4第11外显子与NUT第2外显子的读码框内融合。患者转至另一家医院接受放化疗。
我们在此描述了首例日本鼻窦NMC病例，提供了关于BRD4-NUT重排详细且明确的细胞及分子遗传学信息。积累有充分记录的遗传数据的病例应能为该肿瘤实体的治疗提供线索。
