鼻腔鼻窦非角化性鳞状细胞癌的临床病理学特征

Clinicopathologic features of non-keratinizing carcinoma of nasal cavity and paranasal sinus

目的：探讨鼻腔鼻窦非角化性鳞状细胞癌的临床病理学特征、免疫表型特点及诊断与鉴别诊断。方法收集441例鼻腔鼻窦鳞状细胞癌，选取其中26例非角化性鳞状细胞癌患者的临床及病理检查资料，观察其组织形态学特点，采用免疫组织化学EnVision法对20例行广谱细胞角蛋白（ CKpan）、波形蛋白、CK5／6、CK7、CK8／18、p16、p53、Ki-67等多种标志物染色；以导流杂交等方法检测人乳头状瘤病毒（HPV），以原位杂交方法检测EB病毒编码小mRNA1／2（EBER），以RNAscope方法检测其肿瘤组织内HPV mRNA。结果患者年龄22-79岁，平均年龄51.2岁，男16例，女10例，男女比为8∶5，3例患者有内翻性乳头状瘤的病史。镜下肿瘤组织主要呈乳头状和内翻浸润性生长，似尿路上皮乳头状癌形态；浸润生长部分形成大小不一的实性细胞巢，肿瘤细胞核大圆形，核仁明显，2例可见部分肿瘤细胞呈梭形，1例可见与鼻腔鼻窦被覆纤毛柱状上皮有移行。免疫组织化学染色结果示CKpan及p63（20／20）均为弥漫强阳性；CK5／6在17例为弥漫强阳性，3例为部分阳性；CK8／18在16例弥漫强阳性，3例灶状阳性，1例阴性；CK7在7例弥漫强阳性，13例阴性；波形蛋白在2例部分阳性，18例阴性；p16在1例弥漫强阳性，19例阴性；p53在19例阳性；Ki-67有11例阳性表达超过50％，其他神经内分泌标志物及黑色素瘤标志物为阴性。导流杂交方法检测到1例HPV （6、11、16、18）为阳性，进一步行HPV原位杂交检测，其HPV16／18及6／11阳性，用RNAscope技术检测，结果显示肿瘤组织中HPV18 mRNA阳性。20例EBER原位杂交均呈阴性。本组病例多为5年之内病例，预后有待于进一步随访观察。结论鼻腔鼻窦非角化性鳞状细胞癌是一种罕见的、具有明显形态学特征的上皮性恶性肿瘤，以发生部位、组织学特点为主要诊断依据，免疫组织化学染色标志物可辅助诊断及鉴别诊断；肿瘤可能起源于鼻腔鼻窦被覆纤毛柱状上皮，与HPV及EB病毒感染相关性不明显。

Objective To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of non-keratinizing carcinoma of nasal cavity and paranasal sinus.Methods Four hundred and forty-one cases of squamous cell carcinoma of the nasal cavity and sinuses diagnosed in Beijing Tongren Hospital from January 2008 to August 2015 were included.Twenty-six cases of non-keratinizing carcinomas were selected.The histopathologic features and the clinicopathologic data of these twenty-six cases were retrospectively analyzed.Immunohistochemistry （ two-step EnVision method ） was done to evaluate the expression of CK, vimentin, CK5/6,CK7,CK8/18,p16, p53, Ki-67 etc.In situ hybridization was used to detect Epstein-Barr virus mRNA（EBER）, and flow-through hybridization was used to evaluate the presence of human papilloma virus （ HPV） .One of the cases which HPV is positive was detected by HPV in situ hybridization and RNAscope technology.Results The mean age for the twenty-six patients （16 males, 10 females） was 51.2 years （ range 22 to 79 years）.Three patients had a history of inverted papilloma.Microscopically the tumors showed invasive papillary and inverted growth, and formed solid cell nests with different sizes.It was similar to papillary carcinoma of the urinary tract： the nuclei of the tumor were rounded and the nucleolus are clear.Three cases displayed transition between normal epithelium to neoplastic cells;in two cases （2/26）, some tumor cells were spindle shaped.Twenty cases （20/20） werestrongly positive for CK, p63;17 cases （17/20） were strongly positive for CK5/6 and three cases （3/20） were focally positive.Sixteen cases were strongly positive for CK8/18 and three cases （3/20） were focally positive and one case was negative.Seven cases （ 7/20 ） were strongly positive for CK7 and 13 cases （13/20） were negative.Two cases （2/20） were focally positive for vimentin and eighteen （18/20） cases were negative.One case （1/20） was strongly positive for p16 and nineteen cases （19/20） were negative.Nineteen cases （19/20） were positive for p53 and one case （1/20） was negative.Ki-67 index was 〉50%in 11 cases.Twenty cases （20/20） were negative for AFP, NUT, S-100 protein, HMB45 and Melan A.One case was positive for HPV （6, 11, 16, 18）, as detected by in situ hybridization.The HPV18 mRNA was detected by RNAscope technique.In situ hybridization were negative in all twenty cases.The mean follow-up time of the patients in this group was less than 5 years, and the prognosis needs further observation.Conclusions Non-keratinizing squamous cell carcinoma is a rare neoplasm with distinct morphological characteristics.Its diagnosis is primarily based on the site of lesions and the histological features.Immunohistochemistry staining can aid the diagnosis and differential diagnoses.The tumor may originate from the epithelium of nasal cavity and sinus.This disease has no relation with HPV and EBV infection, and the treatment is primarily surgical excision combined with postoperative radiotherapy.