Department of Pathology, University of California San Diego, La Jolla, CA.
Am J Surg Pathol. 2020 Sep;44(9):1151-1160. doi: 10.1097/PAS.0000000000001472.
A novel 3-tiered grading system that combines tumor budding activity and cell nest size has been found to be highly prognostic in squamous cell carcinomas (SCCs) of various sites, including lung, oral cavity, larynx, hypopharynx, and esophagus. A similar grading system has recently been proposed for SCC of the uterine cervix. In this study, we appraise this grading system in an institutional cohort of cervical SCC to assess its prognostic value in an independent dataset. Our study cohort consisted of 94 consecutive, surgically excised, neoadjuvant therapy-naive cases of SCC of the uterine cervix, stage pT1b or higher. Tumor budding activity and cell nest size were scored on each case, the sum of which formed the basis for assigning a grade in the 3-tiered grading system hereafter referred to as the "tumor budding/nest size" (TBNS) system. As individual variables, both high tumor budding and small nest size were each associated with reduced overall survival (OS), disease-specific survival, and disease-free survival. The full TBNS system was associated with decreased OS, disease-specific survival, and disease-free survival independent of patient age, pathologic stage, and regional lymph node status. TBNS grades 1, 2, and 3 subgroups were clearly distinguishable on multivariate analyses (hazard ratio for OS of 2.06 [95% confidence interval: 0.5-8.42] for grade 2 and 4.58 [95% confidence interval: 1.24-16.87] for grade 3 tumors, relative to their grade 1 counterparts [P=0.035]). Higher grade tumors in the TBNS system were significantly correlated with advanced pathologic stage and lymph node metastasis (P=0.044 and 0.04, respectively). Among the other, potentially prognostic factors, higher pathologic stage, and lymph node metastasis were associated with decreased OS (P<0.001 and 0.004, respectively), whereas keratinization, nuclear size, mitotic count, and World Health Organization (WHO) grade were not. In conclusion, the proposed TBNS grading system is an excellent prognostic indicator that may potentially provide information that is useful in clinical decision-making. Our findings validate the previous study that proposed this system for prognostically stratifying cervical SCC patients. If further confirmed, consideration should be given to routinely adding a TBNS grade to pathologic descriptions of cervical SCC.
一种新的三级分级系统，结合了肿瘤芽殖活动和细胞巢大小，已被发现对各种部位的鳞状细胞癌（SCC）具有高度的预后价值，包括肺、口腔、喉、下咽和食管。最近也提出了一种类似的分级系统用于子宫颈 SCC。在这项研究中，我们评估了该分级系统在一个机构队列中的子宫颈 SCC 中，以评估其在独立数据集的预后价值。我们的研究队列包括 94 例连续、手术切除、新辅助治疗前的 SCC 子宫颈病例，分期为 pT1b 或更高。在每个病例上对肿瘤芽殖活性和细胞巢大小进行评分，其总和构成了在三级分级系统中分配等级的基础，以下简称“肿瘤芽殖/巢大小”（TBNS）系统。作为单个变量，高肿瘤芽殖和小巢大小均与总生存（OS）、疾病特异性生存和无病生存减少相关。完整的 TBNS 系统与 OS、疾病特异性生存和无病生存的降低独立于患者年龄、病理分期和区域淋巴结状态相关。在多变量分析中，TBNS 分级 1、2 和 3 亚组明显可区分（OS 的危险比为 2.06 [95%置信区间：0.5-8.42]，为 2 级，4.58 [95%置信区间：1.24-16.87]，为 3 级肿瘤，与 1 级相比[P=0.035]）。TBNS 系统中较高等级的肿瘤与晚期病理分期和淋巴结转移显著相关（P=0.044 和 0.04，分别）。在其他潜在的预后因素中，较高的病理分期和淋巴结转移与 OS 降低相关（P<0.001 和 0.004，分别），而角化、核大小、有丝分裂计数和世界卫生组织（WHO）分级则不然。总之，提出的 TBNS 分级系统是一种优秀的预后指标，可能提供有助于临床决策的信息。我们的发现验证了之前提出该系统对子宫颈 SCC 患者进行预后分层的研究。如果进一步证实，应考虑将 TBNS 分级常规添加到子宫颈 SCC 的病理描述中。
