There are no universally accepted grading systems in pulmonary squamous cell carcinoma (pSQCC). Recently, tumor budding, cell nest size, and spread through airspaces (STAS) have been proposed as grading scheme candidates. Tumor budding is a well-established independent prognostic factor in colorectal cancer. The International Tumor Budding Consensus Conference (ITBCC) provided consensus on scoring in 2016, albeit for colorectal cancers. Here, we aimed to validate the ITBCC method in pSQCC and evaluate additional proposed grading parameters. We analyzed a fully clinico-pathologically annotated Western single-center cohort of 354 consecutive primary resected pSQCC (resected 2000-2013). Patients with SQCC of other organs were excluded to reliably exclude lung metastases. We assessed conventional grading, keratinization, STAS, and tumor budding according to ITBCC recommendations, and correlated them with clinico-pathological parameters and survival. Tumor budding was low (0-4 buds/0.785 mm2) in 41%, intermediate (5-9 buds/0.785 mm2) in 30%, and high (≥10 buds/0.785 mm2) in 29% of cases (mean bud count = 7.45 (H&E), min = 0, max = 84). Cell nests of 1, 2-4, 5-15, >15 cells were present in 68%, 20%, 5%, 7%, respectively. We detected STAS in 33% of cases, desmoplasia in 68%. Tumor budding assessed as continuous and categorized variables was highly concordant between hematoxylin and eosin (H&E) and pancytokeratin (AE1/AE3) stained slides (P < 0.001) and significantly associated with tumor size, UICC/AJCC pT, pN, stage (all P < 0.001) and presence of mediastinal lymph node metastases (H&E: P = 0.028). Tumor budding was a significant prognostic parameter for overall, disease-specific, and progression-free survival (PFS) (all P < 0.001). ITBCC tumor budding categories were independent prognostic factors for overall survival (HR = 1.581; 95% CI 1.186-2.108; P = 0.002), disease-specific survival (HR = 1.710; 95% CI 1.111-2.632; P = 0.015), and PFS (HR = 1.457; 95% CI 1.123-1.890; P = 0.005). STAS or conventional tumor grade had no prognostic value. In conclusion, we confirm tumor budding as an independent prognostic marker in pSQCC and validate the ITBCC 2016 scoring recommendations in pSQCC.

中文翻译：

---

国际肿瘤萌芽共识会议 (ITBCC) 2016 年肺鳞状细胞癌推荐意见的验证——354 例单中心分析。

肺鳞状细胞癌 (pSQCC) 没有普遍接受的分级系统。最近，肿瘤出芽、细胞巢大小和空间扩散 (STAS) 已被提议作为分级方案的候选。肿瘤出芽是结直肠癌中公认的独立预后因素。国际肿瘤萌芽共识会议 (ITBCC) 在 2016 年就评分达成了共识，尽管是针对结直肠癌。在这里，我们旨在验证 pSQCC 中的 ITBCC 方法并评估其他建议的分级参数。我们分析了 354 例连续原发切除的 pSQCC（2000-2013 年切除）的完全临床病理学注释的西方单中心队列。排除其他器官的 SQCC 患者以可靠地排除肺转移。我们评估了常规分级、角化、STAS、和肿瘤出芽根据 ITBCC 的建议，并将它们与临床病理参数和生存相关联。41% 的肿瘤出芽为低（0-4 个芽/0.785 mm2），30% 为中间（5-9 个芽/0.785 mm2），29% 的病例为高（≥10 个芽/0.785 mm2）（平均芽数= 7.45 (H&E)，最小值 = 0，最大值 = 84)。1、2-4、5-15、>15 个细胞的细胞巢分别占 68%、20%、5%、7%。我们在 33% 的病例中检测到 STAS，在 68% 的病例中检测到结缔组织增生。评估为连续变量和分类变量的肿瘤出芽在苏木精和伊红 (H&E) 和泛细胞角蛋白 (AE1/AE3) 染色载玻片之间高度一致 (P < 0.001)，并且与肿瘤大小、UICC/AJCC pT、pN、分期显着相关（所有 P < 0.001) 和存在纵隔淋巴结转移 (H&E: P = 0.028)。肿瘤出芽是总体、疾病特异性和无进展生存期 (PFS) 的重要预后参数（所有 P < 0.001）。ITBCC 肿瘤出芽类别是总生存期（HR = 1.581；95% CI 1.186-2.108；P = 0.002）、疾病特异性生存期（HR = 1.710；95% CI 1.111-2.632；P = 0.015）和PFS（HR = 1.457；95% CI 1.123-1.890；P = 0.005）。STAS 或常规肿瘤分级没有预后价值。总之，我们确认肿瘤出芽是 pSQCC 中的独立预后标志物，并验证了 pSQCC 中的 ITBCC 2016 评分建议。95% 置信区间 1.111-2.632；P = 0.015）和 PFS（HR = 1.457；95% CI 1.123-1.890；P = 0.005）。STAS 或常规肿瘤分级没有预后价值。总之，我们确认肿瘤出芽是 pSQCC 中的独立预后标志物，并验证了 pSQCC 中的 ITBCC 2016 评分建议。95% 置信区间 1.111-2.632；P = 0.015）和 PFS（HR = 1.457；95% CI 1.123-1.890；P = 0.005）。STAS 或常规肿瘤分级没有预后价值。总之，我们确认肿瘤出芽是 pSQCC 中的独立预后标志物，并验证了 pSQCC 中的 ITBCC 2016 评分建议。