Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, 9200293, Japan; Department of Diagnostic Pathology, Ishikawa Prefectural Central Hospital, Ishikawa, 9208201, Japan.
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, 9200293, Japan; Division of Tumor Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui, 9101104, Japan.
Hum Pathol. 2018 Jan;71:157-165. doi: 10.1016/j.humpath.2017.10.011. Epub 2017 Oct 24.
Nuclear protein in testis (NUT) carcinoma is a rare malignant neoplasm with an undifferentiated morphology. Its diagnosis is often difficult, especially as the sinonasal tract gives rise to many tumors with undifferentiated morphologies. Not many cases of sinonasal NUT carcinomas have been reported, and its clinicopathological features have not been sufficiently clarified. In this study, we performed a clinicopathological study of 4 patients with sinonasal NUT carcinoma, including wide-ranging immunohistochemical tests and cytogenetic analyses using fluorescence in situ hybridization and DNA sequencing. Autopsy findings were obtained from 2 patients. Patients' ages ranged from 9 months to 66 years (median, 37 years). Three cases involved the nasal cavity; of these, 2 also involved the ethmoid sinus. One case only involved the frontal sinus. Histologically, all cases revealed undifferentiated small round cell morphology and necrosis with indistinct cell borders, vesicular chromatin, and distinct nucleoli. All patients received chemoradiotherapy; 3 died of disease 10 to 15 months after their diagnoses, while one was lost to follow-up. The 2 autopsied patients showed multiorgan metastases; interestingly, one showed cartilaginous differentiation in a metastatic lesion. Immunohistochemically, all cases were diffusely positive for NUT, p63, and Myc, and were focal for p40. The cells variably expressed epithelial markers, and CD34 was positive in one patient. Cytogenetically, all showed BRD4-NUT fusion genes, but one had a different breakpoint in each exon. Finally, a literature review indicated that sinonasal NUT carcinoma tends to involve frontal and ethmoidal sinuses more frequently than other sinonasal cancers.
睾丸核蛋白（NUT）癌是一种罕见的未分化形态恶性肿瘤。其诊断通常较为困难，尤其是在发生于鼻腔鼻窦的肿瘤中，许多肿瘤也具有未分化的形态。目前报道的鼻腔鼻窦 NUT 癌病例较少，其临床病理特征尚未得到充分阐明。本研究对 4 例鼻腔鼻窦 NUT 癌患者进行了临床病理研究，包括广泛的免疫组织化学检测和应用荧光原位杂交及 DNA 测序的细胞遗传学分析。2 例患者有尸检结果。患者年龄 9 个月至 66 岁（中位数，37 岁）。3 例累及鼻腔，其中 2 例也累及筛窦。1 例仅累及额窦。组织学上，所有病例均显示未分化的小圆细胞形态和坏死，细胞边界不清，核染色质呈泡状，核仁明显。所有患者均接受了放化疗；3 例患者在诊断后 10 至 15 个月因疾病死亡，1 例失访。2 例尸检患者均有多个器官转移；有趣的是，1 例转移灶中出现软骨分化。免疫组织化学染色均弥漫性表达 NUT、p63 和 Myc，p40 灶性表达。细胞不同程度表达上皮标志物，1 例 CD34 阳性。细胞遗传学显示所有患者均存在 BRD4-NUT 融合基因，但 1 例每个外显子的断裂点均不同。最后，文献复习表明鼻腔鼻窦 NUT 癌较其他鼻腔鼻窦癌更常累及额窦和筛窦。
