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Bridging the gap between tumor evolution and clonality diagnostics in multiple lung carcinomas.

Jurriaan Janssen1, Michael Allgäuer2, Bauke Ylstra3

  • 1Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Seminars in Cancer Biology
|March 30, 2026
PubMed
Summary

Distinguishing multiple primary lung cancers from metastases is crucial for patient treatment. Integrating tumor evolution insights with molecular diagnostics improves accuracy in non-small cell lung cancer (NSCLC) clonality assessment.

Keywords:
Clonality diagnosticsIntrapulmonary metastasesMultiple primary lung carcinomasNon-small cell lung cancerTumor evolution

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Pathology

Background:

  • Differentiating multiple primary lung carcinomas (MPLCs) from intrapulmonary metastases (IPMs) presents a significant clinical challenge in non-small cell lung cancer (NSCLC) management.
  • While clinically similar, MPLCs and IPMs arise from distinct evolutionary pathways, necessitating precise diagnostic tools.

Purpose of the Study:

  • To bridge the gap between tumor evolution principles and clonality diagnostics in NSCLC.
  • To review historical and modern approaches for distinguishing MPLICs from IPMs using genomic insights.

Main Methods:

  • Systematic review of diagnostic approaches informed by tumor evolution.
  • Analysis of histomorphology, somatic mutation profiling, fusion detection, copy number analysis, transcriptomics, and methylation testing.
  • Revisiting historical clonality diagnostics from a genomic perspective.

Main Results:

  • Genomic research elucidates tumor evolutionary dynamics, providing a framework for clonality diagnostics.
  • Established and emerging molecular pathology techniques reflect oncogenesis evolutionary principles.
  • Conceptual integration of tumor evolution enhances diagnostic accuracy.

Conclusions:

  • Accurate clonality diagnostics are essential for precise staging and optimal treatment selection in patients with multiple lung carcinomas.
  • Understanding tumor evolution is key to improving patient outcomes in NSCLC.
  • Molecular pathology and evolutionary principles offer powerful tools for clinical decision-making.