Lewis J S, Chernock R D, Bishop J A
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA.
Head Neck Pathol. 2018 Mar;12(1):62-70. doi: 10.1007/s12105-017-0825-y. Epub 2017 May 20.
The performance characteristics of neuroendocrine-specific and squamous-specific immunohistochemical markers in head and neck squamous cell carcinomas (SCC), in particular in oropharyngeal tumors in this era of human papillomavirus (HPV)-induced cases, are not well-established. The differential diagnosis for poorly differentiated SCCs, for nonkeratinizing oropharyngeal SCCs, and for other specific SCC variants such as basaloid SCC and undifferentiated (or lymphoepithelial-like) carcinomas includes neuroendocrine carcinomas. Given that neuroendocrine carcinomas of the head and neck are aggressive regardless of HPV status, separating them from SCC is critically important. In this study, we examined the neuroendocrine markers CD56, synaptophysin, and chromogranin-A along with the squamous markers p40 and cytokeratin 5/6 in a large tissue microarray cohort of oral, oropharyngeal, laryngeal, and hypopharyngeal SCCs with known HPV results by RNA in situ hybridization for the oropharyngeal tumors. Results were stratified by site and specific SCC variant. The neuroendocrine stains were rarely expressed in SCC (<1% overall) with CD56 the least, and chromogranin-A the most, specific markers. Further, p40 and cytokeratin 5/6 were very consistently expressed in all head and neck SCC (>98% overall), including very strong, consistent staining in oropharyngeal HPV-related nonkeratinizing SCC. Undifferentiated (or lymphoepithelial-like) carcinomas of the oropharynx are more frequently p40 or cytokeratin 5/6 negative or show only weak or focal expression. In summary, markers of neuroendocrine and squamous differentiation show very high specificity and sensitivity, respectively, across the different types of head and neck SCC.
神经内分泌特异性和鳞状特异性免疫组化标志物在头颈部鳞状细胞癌（SCC）中的表现特征，尤其是在人乳头瘤病毒（HPV）引发病例的这个时代的口咽肿瘤中，尚未完全明确。对于低分化SCC、非角化性口咽SCC以及其他特定的SCC变体，如基底样SCC和未分化（或淋巴上皮样）癌，其鉴别诊断包括神经内分泌癌。鉴于头颈部神经内分泌癌无论HPV状态如何都具有侵袭性，将它们与SCC区分开来至关重要。在本研究中，我们在一个大型组织芯片队列中检测了神经内分泌标志物CD56、突触素和嗜铬粒蛋白A，以及鳞状标志物p40和细胞角蛋白5/6，该队列包含口腔、口咽、喉和下咽SCC，通过RNA原位杂交对头颈部肿瘤进行HPV检测。结果按部位和特定SCC变体进行分层。神经内分泌染色在SCC中很少表达（总体<1%），其中CD56表达最少，嗜铬粒蛋白A表达最多，是特异性标志物。此外，p40和细胞角蛋白5/6在所有头颈部SCC中表达非常一致（总体>98%），包括在口咽HPV相关非角化性SCC中呈非常强且一致的染色。口咽部未分化（或淋巴上皮样）癌更常出现p40或细胞角蛋白5/6阴性，或仅表现为弱或局灶性表达。总之，神经内分泌和鳞状分化标志物在不同类型的头颈部SCC中分别显示出非常高的特异性和敏感性。
