A Grading System of Lung Adenocarcinomas Based on Histologic Pattern is Predictive of Disease Recurrence in Stage I Tumors

Abstract

Currently no objective grading system for pulmonary adenocarcinomas exists. To determine whether specific histologic patterns or combinations thereof could be linked to an objective grading system, the histologic patterns in metastatic tumor deposits was compared with the patterns seen in the corresponding 73 primary tumor to determine whether a specific pattern had higher propensity to metastasize. The concordance of the predominant histologic pattern in the primary tumor and the metastases was of 100% for micropapillary, 86% for solid, 42% for acinar, and 23% for papillary types of adenocarcinoma. Informed by these results, a 3-tier grading system based on the histologic subtypes was established. Grade I, a pattern with low metastatic potential (BAC); Grade II, patterns with intermediate metastatic potential (acinar and papillary); and Grade III, patterns with high metastatic potential (solid and micropapillary). These grades were combined into a number of different scoring systems, whose ability to predict recurrence or death from disease was tested in 366 stage 1 adenocarcinomas. A score based on the 2 most predominant grades was able to stratify patients into low-to-high risk for recurrence or death of disease (P=0.001). The 5-years disease-free survival for patients in the highest score group was of 0.73, compared with 0.84 and 0.92 in the intermediate and lowest score groups. Concordance probability estimate was 0.65 (95% confidence interval 0.57-0.73). Therefore, this scoring system provides valuable information in discriminating patients with different risk of disease-recurrence in a highly homogeneous population of patients with stage I cancer.

Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases

“…Not only do these histological subtypes fall into overall prognostic categories or grades of behavior as we demonstrate in this study, but Sica G et al have shown that the detailed data derived from comprehensive histological subtyping appear to be useful for developing a more elaborate grading system for lung adenocarcinoma according to tumor architecture. 24 In our series, the adenocarcinoma in situ and MIA cases comprised less than 2%, the 29 lepidic predominant adenocarcinomas, comprised 5.6%, and the remaining 93% of cases represented predominantly invasive adenocarcinomas. These predominantly invasive adenocarcinomas, comprise the largest subset of tumors and presented the greatest challenge of this new classification because they are composed of a complex heterogeneous mixture of the different histological patterns.…”

Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas

“…In spite of these differences, the solid, micropapillary, and cribriform patterns were all classified as 'high-grade' patterns with increased metastatic potential by a recently proposed histologic grading system for lung adenocarcinomas. 27 Therefore, regardless of the apparent morphologic differences among the various studies, there seems to be agreement that ALK þ tumors tend to adopt an aggressive histologic pattern.…”

“…As solid and micropapillary patterns of lung adenocarcinoma have been reported to have an increased propensity for metastasis, it is possible that any statistical predilection that ALK þ tumors show for a solid or micropapillary pattern is diminished by the overall higher prevalence of solid and micropapillary patterns at metastatic sites. 22,23,27 Although ALK þ primary lung adenocarcinomas were associated with the presence of hepatoid tumor cells and psammoma bodies, these associations also failed to be preserved in metastatic tumors. It is currently unclear why these morphologic features help distinguish ALK rearrangements in primary lung tumors but not in metastatic tumors.…”

Surgical pathology of early stage non-small cell lung carcinoma

“…As stated previously, studies have shown that solid and micropapillary predominant tumors have the worst prognosis among the histologic subtypes. Additional evidence suggests that the micropapillary pattern may in and of itself be a robust predictor of both prognosis and survival (14,20) and associated with poor outcomes (21,37). Furthermore, it has recently been suggested that the presence or absence of the micropapillary pattern may be an important prognostic indicator and impact survival (32)(33)(34).…”