Abstract：
Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, n = 136) and Lausanne (2005-2020, n = 113) with available preoperative biopsies was analyzed for TB and additional histomorphologic parameters, such as spread through airspaces and desmoplasia, by 2 expert pathologists (M.M., C.N.). Results were correlated with clinicopathologic parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4%, and high (≥10 buds/0.785 mm2) in 25% of cases (median bud count, 5; IQR, 0-26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (P = .192) but significantly different from the score obtained in the biopsy (P < .001). Interobserver variability was moderate, regardless of score location (Cohen kappa, 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (P = .002), presence of lymph node (P = .033), and distant metastases (P = .020), without significant correlation with overall survival, tumor size, or pleural invasion. Desmoplasia was significantly associated with higher PTB (P < .001). Spread through airspaces was present in 34% and associated with lower PTB (P < .001). To conclude, despite confirming TB as a reproducible factor in LUSC, we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final TB score of the resected tumor.
摘要：
肺鳞状细胞癌（LUSC）的分级是有争议的，并没有被普遍接受。肿瘤出芽（TB）的组织形态学特征是结直肠癌中已确立的独立预后因素，其重要性在其他实体癌中越来越重要。使其成为纳入肿瘤分级计划的候选人。我们旨在比较肺鳞状细胞癌的术前活检和切除标本之间的TB，并评估观察者之间的变异性。在伯尔尼（2000-2013年，N=136）和洛桑（2005-2020年N=113）接受LUSC切除的249例连续患者的回顾性队列中，分析了可用的术前活检的结核病和其他组织形态学参数，例如通过气道传播（STAS）和组织增生由两名专家病理学家。结果与临床病理参数和生存率相关。在切除标本中，肿瘤周围出芽（PTB）评分较低（0-4芽/0.785mm2），占47.6％，中间（5-9芽/0.785mm2）为27.4%，和高（≥10芽/0.785mm2）在25％的情况下（中位芽计数=5，IQR=0-26）。当比较肿瘤边缘和肿瘤内区时，芽的绝对数量和TB评分相似（p=0.192），但与活检中获得的评分显着不同（p<0.001）。观察者间的变异性中等，无论分数位置(科恩的卡帕0.59)。对不一致的案件进行了重新评估，在所有案件中都达成了共识，并确定了不一致的原因。TB评分与分期显著相关(p=0.002),淋巴结（p=0.033）和远处转移（p=0.020）的存在，与总生存率无显著相关性，肿瘤大小或胸膜侵犯。组织增生与较高的PTB显著相关(p<0.001)。STAS占34％，与较低的PTB相关（p<0.001）。最后，尽管在LUSC中证实了TB是一个可重复的因素,但我们发现了评分模糊的领域.术前活检评估不足以确定切除肿瘤的最终肿瘤出芽评分。
