Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
J Clin Pathol. 2022 Jun;75(6):390-396. doi: 10.1136/jclinpath-2021-207421. Epub 2021 Mar 1.
Various approaches have been reported for distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases in patients with two lung nodules. The aim of this study was to determine whether histological assessment is reliable and accurate in distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases using routine molecular findings as an adjunct.
We studied resected tumour pairs from 32 patients with lung adenocarcinomas in different lobes. In 15 of 32 tumour pairs, next-generation sequencing (NGS) for common driver mutations was performed on both nodules. The remainder of tumour pairs underwent limited NGS, or genotyping. Tumour pairs with different drivers (or one driver/one wild-type) were classified as molecularly unrelated, while those with identical low-frequency drivers were classified as related. Three pathologists independently and blinded to the molecular results categorised tumour pairs as related or unrelated based on histological assessment.
Of 32 pairs, 15 were classified as related by histological assessment, and 17 as unrelated. Of 15 classified as related by histology, 6 were classified as related by molecular analysis, 4 were unrelated and 5 were indeterminate. Of 17 classified as unrelated by histology, 14 were classified as unrelated by molecular analysis, none was related and 3 were indeterminate. Histological assessment of relatedness was inaccurate in 4/32 (12.5%) tumour pairs.
A small but significant subset of two-nodule adenocarcinoma pairs is inaccurately judged as related by histological assessment, and can be proven to be unrelated by molecular analysis (driver gene mutations), leading to significant downstaging.
已有多种方法用于区分患者肺部两个结节中的孤立性原发性肺腺癌与肺内转移。本研究旨在确定组织学评估结合常规分子检测结果在区分孤立性原发性肺腺癌与肺内转移方面是否可靠和准确。
我们研究了 32 例不同肺叶肺腺癌患者的切除肿瘤对。在 32 对肿瘤中，有 15 对进行了下一代测序（NGS）以检测常见驱动基因突变。其余肿瘤对进行了有限 NGS 或基因分型。具有不同驱动基因（或一个驱动基因/一个野生型）的肿瘤对被归类为分子上不相关，而具有相同低频驱动基因的肿瘤对被归类为相关。3 位病理学家独立且不了解分子结果，根据组织学评估将肿瘤对归类为相关或不相关。
在 32 对中，15 对根据组织学评估被归类为相关，17 对为不相关。在通过组织学评估归类为相关的 15 对中，有 6 对通过分子分析归类为相关，4 对不相关，5 对不确定。在通过组织学评估归类为不相关的 17 对中，有 14 对通过分子分析归类为不相关，没有一对为相关，有 3 对不确定。组织学相关性评估在 4/32（12.5%）对肿瘤中不准确。
一小部分（但有统计学意义）两个结节腺癌对通过组织学评估被错误地判断为相关，而通过分子分析（驱动基因突变）可证明为不相关，从而导致分期显著降级。
