Background: Squamous cell carcinoma (SCC) is a heterogeneous group of epithelial malignancies with varied morphologies and clinical behaviors. While histopathology is the diagnostic gold standard, it can be limited in distinguishing SCC from morphologic mimics. Immunohistochemistry (IHC) has therefore become a critical adjunct, enhancing diagnostic accuracy and providing prognostic insights. Objective: This narrative review aims to evaluate the diagnostic, differential, and prognostic roles of commonly used IHC markers in SCC, with particular emphasis on their utility in distinguishing SCC from histologic mimickers across different anatomical sites. Methods: One hundred and five peer-reviewed articles were analyzed for their relevance to the immunohistochemical characterization of SCC. Markers were categorized based on their diagnostic function, role in differential diagnosis, and prognostic value. Results: Key markers such as p40, p63, CK5/6, and DSG3 consistently demonstrated high sensitivity and specificity for SCC, reinforcing their value in confirming squamous differentiation. Conversely, exclusion markers like Ber-EP4, CK7, TTF-1, S100, and SOX10 were essential in ruling out basal cell carcinoma, adenocarcinoma, and melanoma. Additionally, markers such as Ki-67, p16, and CD44 offered prognostic information regarding tumor aggressiveness, HPV status, and therapy response. These findings confirm the critical role of IHC not only in diagnosing SCC but also in resolving complex differential diagnoses. Conclusions: IHC markers serve as indispensable tools in the diagnostic workup of SCC, particularly in distinguishing it from other neoplasms with overlapping histologic features. The clear correlation between marker expression and diagnostic categories supports the systematic use of IHC to improve diagnostic precision and inform prognosis. Future integration with molecular diagnostics may further refine personalized treatment approaches in SCC.
背景：鳞状细胞癌（SCC）是一组具有不同形态学和临床行为的异质性上皮恶性肿瘤。虽然组织病理学是诊断的金标准，但在区分SCC与形态学相似病变方面存在局限性。因此，免疫组织化学（IHC）已成为关键的辅助手段，可提高诊断准确性并提供预后信息。目的：本文旨在评估常用IHC标志物在SCC中的诊断、鉴别诊断及预后作用，特别强调其在不同解剖部位区分SCC与组织学相似病变中的应用价值。方法：分析了105篇与SCC免疫组化特征相关的同行评议文献。根据标志物的诊断功能、鉴别诊断作用及预后价值进行分类。结果：p40、p63、CK5/6和DSG3等关键标志物对SCC始终表现出高敏感性和特异性，强化了其在确认鳞状分化的价值。相反，Ber-EP4、CK7、TTF-1、S100和SOX10等排除性标志物在排除基底细胞癌、腺癌和黑色素瘤中至关重要。此外，Ki-67、p16和CD44等标志物可提供关于肿瘤侵袭性、HPV状态和治疗反应的预后信息。这些发现证实了IHC不仅在诊断SCC中，而且在解决复杂鉴别诊断中均具有关键作用。结论：IHC标志物是SCC诊断过程中不可或缺的工具，特别是在区分具有重叠组织学特征的其他肿瘤方面。标志物表达与诊断类别之间的明确关联支持系统化应用IHC以提高诊断精度并指导预后。未来与分子诊断学的整合可能进一步优化SCC的个体化治疗策略。
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