鳞状细胞癌 (SCC) 是肺非小细胞癌的主要类别之一，分为角化性鳞状细胞癌、非角化性鳞状细胞癌和基底细胞样鳞状细胞癌。仅使用角化性鳞状细胞癌的组织形态学即可轻松诊断鳞状细胞癌。验证性免疫组织化学分析应始终应用于非角化性肿瘤和基底细胞样肿瘤，以排除鉴别诊断，最显着的是腺癌和高级别神经内分泌癌，这可能产生重要的治疗效果。根据世界卫生组织 (WHO) 2015 年分类，鳞状细胞癌的诊断可通过切除形态不明确的鳞状免疫表型肿瘤来诊断。在相同环境下的活检和细胞学准备中，当前指南建议在 TTF1 阴性和 p40 阳性肿瘤中诊断为“非小细胞癌，倾向于 SCC”，以承认可能存在的采样偏差并限制扩展的免疫组织化学评估，以便保存组织用于分子测试。大多数鳞状细胞癌都具有分子“烟草烟雾特征”，其中富含 GG > TT 突变，这与鳞状细胞癌与吸烟之间的强烈流行病学关联一致。靶向突变极为罕见，但确实发生，特别是在年轻和不吸烟或轻度吸烟的患者中，需要进行分子研究。淋巴上皮癌 (LEC) 是一种低分化鳞状细胞癌，具有合胞体生长模式，通常有显着的淋巴浆细胞浸润，且经常伴有 Epstein-Barr 病毒 (EBV)。在这篇综述中，我们描述了 SCC 和 LEC 的形态和分子特征，并讨论了最相关的鉴别诊断。© 2023 作者。组织病理学由约翰·威利出版

Squamous cell carcinoma (SCC) comprises one of the major groups of non-small-cell carcinoma of the lung, and is subtyped into keratinising, non-keratinising and basaloid SCC. SCC can readily be diagnosed using histomorphology alone in keratinising SCC. Confirmatory immunohistochemical analyses should always be applied in non-keratinising and basaloid tumours to exclude differential diagnoses, most prominently adenocarcinoma and high-grade neuroendocrine carcinoma, which may have important therapeutic consequences. According to the World Health Organisation (WHO) classification 2015, the diagnosis of SCC can be rendered in resections of morphologically ambiguous tumours with squamous immunophenotype. In biopsies and cytology preparations in the same setting the current guidelines propose a diagnosis of 'non-small-cell carcinoma, favour SCC' in TTF1-negative and p40-positive tumours to acknowledge a possible sampling bias and restrict extended immunohistochemical evaluation in order to preserve tissue for molecular testing. Most SCC feature a molecular 'tobacco-smoke signature' with enrichment in GG > TT mutations, in line with the strong epidemiological association of SCC with smoking. Targetable mutations are extremely rare but they do occur, in particular in younger and non- or light-smoking patients, warranting molecular investigations. Lymphoepithelial carcinoma (LEC) is a poorly differentiated SCC with a syncytial growth pattern and a usually prominent lymphoplasmacytic infiltrate and frequent Epstein-Barr virus (EBV) association. In this review, we describe the morphological and molecular characteristics of SCC and LEC and discuss the most pertinent differential diagnoses.© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.