[Nasopharyngeal carcinoma with non-squamous immunophenotype: a clinicopathological analysis of 23 cases].

Objective: To investigate the pathological subtypes and clinicopathological characteristics of the non-squamous immunophenotype nasopharyngeal carcinoma (NSNPC). Methods: The clinicopathological features of the non-squamous immunophenotype nasopharyngeal carcinoma diagnosed between 2011 and 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, transmission electron microscopy and PCR gene rearrangement. Follow-up data were also collected. Results: There were 14 males and 9 females with a median age of 46 years (ranging from 16 to 76 years) with an average age of 45 years. Microscopically, patterns were similar to the classic nasopharyngeal carcinoma. Immunohistochemistry showed that most NSNPC cases expressed low molecular weight keratin (CK8/18, CK8 and CKL) and expressed pathway proteins in a low level (EGFR, PI3K, p-AKT and p-mTOR), which had significant difference from classic nasopharyngeal carcinoma group (P<0.05). Other proteins including CK5/6, CKpan, CK7, Syn, CD56, CgA, SOX-10, AKT, mTOR, Notch, STAT3 and p-STAT3 showed no statistical difference between the two groups. Pathogen detection showed that EBER was positive (18/23, 78.3%) and HPV positive(2/23, 8.7%)which were HPV35 and HPV38. The cancer suppressor gene BLU was highly expressed in NSNPC; RASSF1 and Rbms3 were less expressed in NSNPC, in line with classic NPC. As a whole, NSNPC was characterized by ultrastructures of low-differentiated squamous cell carcinoma. Compared with classic nasopharyngeal carcinoma, NSNPC had a lower recurrence rate and earlier clinical stage(P<0.05),but there was no significant correlation with age, sex, distant metastasis and death (P>0.05). Conclusions: The histological morphology, etiology and gene changes of NSNPC are similar to those of classical nasopharyngeal carcinoma and ultrastructural findings show that NSNPC still belongs to undifferentiated type in non-keratinized squamous cell carcinoma. The malignant degree of NSNPC is low and the prognosis is good.目的： 探讨非鳞状免疫表型鼻咽癌（NSNPC）的病理分型及其临床病理特征。 方法： 收集郑州大学第一附属医院2011至2019年经病理确诊为NSNPC的病例，应用HE及免疫组织化学染色、原位杂交、透射电镜及聚合酶链反应（PCR）分析其病理学特点，并收集临床随访资料。 结果： （1）23例NSNPC中男性14例，女性9例，年龄范围16~76岁，中位年龄46岁，平均年龄为45岁。（2）形态学上均与经典鼻咽癌镜下形态相似。（3）免疫组织化学结果：NSNPC多表达低分子质量细胞角蛋白（CK8/18、CK8、CKL），与经典鼻咽癌组比较，差异具有统计学意义（P<0.05）；通路蛋白EGFR、PI3K、p-AKT、p-mTOR在NSNPC中低表达，与经典鼻咽癌组比较，差异具有统计学意义（P<0.05）；其他蛋白CK5/6、广谱细胞角蛋白（CKpan）、CK7、突触素、CD56、嗜铬粒素A（CgA）、SOX-10、AKT、mTOR、Notch、STAT3、p-STAT3与经典鼻咽癌组之间差异均无统计学意义（P>0.05）。（4）病原学检测：EBER阳性率78.3%（18/23），HPV阳性率8.7%（2/23），分别为HPV35及HPV38型。（5）基因改变：相较于经典鼻咽癌，抑癌基因BLU在NSNPC组织中表达增强；抑癌基因RASSF1及Rbms3在NSNPC组织中表达减弱，与经典鼻咽癌表达一致。（6）超微结构特征：5例中发现细胞之间有桥粒连接，余18例未见明显桥粒连接。（7）分期及预后：NSNPC与经典鼻咽癌相比，NSNPC复发率低、临床分期较早（P<0.05），预后较好，而与年龄、性别、远处转移、死亡无明显相关性（P>0.05）。 结论： NSNPC在组织学形态、病原学及基因改变上均与经典鼻咽癌类似，NSNPC仍属于非角化鳞癌中的未分化型。NSNPC恶性程度较低，预后较好。.