Zhao Y H, Bai Y P, Mao M L, Zhang H, Zhao X L, Yang D M, Wan H F, Liu H G
Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing 100730, China.
Zhonghua Bing Li Xue Za Zhi. 2019 Feb 8;48(2):127-131. doi: 10.3760/cma.j.issn.0529-5807.2019.02.010.
To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis. Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18). The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA. OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.
观察口咽鳞状细胞癌伴人乳头瘤病毒感染（OPSCC-HPV）的临床病理特征，探讨不同原位杂交（ISH）检测方法检测HPV在病理诊断中的作用及价值。收集首都医科大学附属北京同仁医院病理科2016年1月至2018年8月间15例OPSCC-HPV病例。这些病例均按照世界卫生组织头颈部肿瘤分类标准进行诊断。对其组织病理学特征及临床病理资料进行回顾性分析。采用免疫组织化学（两步EnVision法）检测p16、Ki-67和p53的表达。采用ISH检测HPV DNA（6/11和16/18型）。采用RNAscope技术评估HPV mRNA（16和18型）的存在情况。15例患者（8例男性，7例女性）的平均年龄为47岁（范围30至69岁）。OPSCC-HPV通常表现为临床晚期，6例有颈部淋巴结肿大（肿大且呈囊性），7例有扁桃体肿大，1例舌根部有肿瘤，1例有吞咽痛。显微镜下，肿瘤呈现出独特的非角化鳞状细胞癌形态。颈部淋巴结转移灶肿大且呈囊性，淋巴结包膜增厚。OPSCC-HPV起源于隐窝上皮，呈巢状和小叶状延伸至扁桃体表面上皮下方，常伴有中央坏死。肿瘤细胞显示高核质比、高有丝分裂率和凋亡率。肿瘤巢常包埋于淋巴样间质内，可被淋巴细胞浸润。15例（15/15）p16呈强阳性；Ki-67指数为60%-90%；p53呈局灶性阳性或阴性。10例（10/10）HPV 6/11 DNA为阴性，1例（1/10）HPV16/18 DNA呈局灶性阳性。11例（11/11）HPV16 mRNA呈强阳性，1例HPV18 mRNA呈局灶性阳性。OPSCC-HPV是一种在病理和临床上具有独特表现的头颈部鳞状细胞癌。所有病例中的OPSCC-HPV均与高危型HPV（16型）相关。采用RNAscope检测高危型HPV16 mRNA对最终诊断和病原体鉴定具有重要意义。
