Berezowska Sabina, Maillard Marie, Keyter Mark, Bisig Bettina
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Histopathology. 2024 Jan;84(1):32-49. doi: 10.1111/his.15076. Epub 2023 Nov 7.
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.
鳞状细胞癌（SCC）是肺非小细胞癌的主要类型之一，可细分为角化型、非角化型和基底样SCC。角化型SCC仅通过组织形态学即可轻松诊断。对于非角化型和基底样肿瘤，应始终进行免疫组化分析以排除鉴别诊断，最主要的是腺癌和高级别神经内分泌癌，这可能会产生重要的治疗后果。根据世界卫生组织（WHO）2015年分类，对于具有鳞状免疫表型的形态学不明确肿瘤的切除标本，可诊断为SCC。在相同情况下的活检和细胞学标本中，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”，以承认可能存在的取样偏差，并限制广泛的免疫组化评估，以便保留组织用于分子检测。大多数SCC具有分子“烟草烟雾特征”，GG>TT突变富集，这与SCC与吸烟的强烈流行病学关联一致。可靶向的突变极为罕见，但确实存在，特别是在年轻以及不吸烟或轻度吸烟的患者中，因此需要进行分子检测。淋巴上皮癌（LEC）是一种低分化SCC，具有合体生长模式，通常有明显的淋巴浆细胞浸润，且常与爱泼斯坦-巴尔病毒（EBV）相关。在本综述中，我们描述了SCC和LEC的形态学和分子特征，并讨论了最相关的鉴别诊断。
