A modified adenocarcinoma classification approach may enhance reproducibility and may be an improvement on the existing World Health Organization (WHO) classification system, according to findings presented by Thunnissen et al at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (Abstract PL03.07).
Study Methods and Results
In the new study, investigators conducted a case-control study involving 70 resected adenocarcinomas measuring up to 3 cm with the goal of establishing a baseline and examining the potential for an improved classification system aided by biomarker analysis. The new research comes after the IASLC Pathology Committee acknowledged the challenges in accurately assigning invasion status based on the criteria outlined in the WHO classification of pulmonary adenocarcinomas.
The modified classification system factored in iatrogenic collapsed adenocarcinomas in situ, identified through elastin and cytokeratin 7 staining. Pathologists initially assessed the cases according to the WHO criteria but subsequently underwent a tutorial, after which they scored the cases based on the modified classification system. A heatmap analysis was conducted to identify areas commonly or less frequently identified as invasive.
The investigators asked for the participation of 42 pathologists across 13 countries who scored the cases in three rounds with respective kappa values of 0.27, 0.45, and 0.62. The results of the scoring indicated that the standard WHO criteria for determining invasion faced challenges in achieving consistent and reproducible results.
However, the modified classification system exhibited notably higher reproducibility. The investigators found that the pathologists displayed a greater increase in competence—reflected by a higher kappa score—when evaluated blindly (0.45) and with guidance (0.62). The outcomes suggested that the revised classification system may overcome the limitations of the WHO criteria, thereby addressing concerns about inconsistent assessments.
Additionally, the investigators revealed that cases scored with "no-invasion" consensus in the second and third rounds achieved a 100% recurrence-free survival rate. The diagnosis of adenocarcinomas in situ after resection with the modified classification system implied that the patients were cured. In contrast, with the diagnosis of invasive adenocarcinomas in these cases based on the WHO classification system, the patients had to live with the possibility of recurrence.
Further bolstering the modified classification system, biomarker analyses associated with invasion and poor outcomes were conducted. These analyses unveiled positive correlations, including a low proliferation rate in adenocarcinomas in situ compared with invasive adenocarcinomas and the presence of TP53 mutations in invasive adenocarcinomas—underscoring their role as late-stage events.
Conclusions
“Our findings suggest that the modified adenocarcinoma classification [system] significantly enhances reproducibility and aligns better with the clinical reality. These results open new avenues for refining our understanding of these cancers and improving patient care,” highlighted lead study author Erik Thunnissen, MD, PhD, in the Department of Pathology at the Amsterdam University Medical Centers. “These findings could enable a more confident diagnosis and treatment decisions for patients with pulmonary adenocarcinomas,” he concluded.
