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Role of Cytomorphology in the Era of Liquid Biopsy

Eduardo Clery1, Pasquale Pisapia1, Elena Vigliar1

  • 1Department of Public Health, University of Naples Federico II, Naples, Italy.

Acta Cytologica
|April 4, 2019
PubMed

Insights

Detecting epidermal growth factor receptor (EGFR) mutations is crucial for non-small cell lung cancer treatment. Morphological changes in cancer cells can indicate resistance to tyrosine kinase inhibitors (TKIs), highlighting the importance of cytopathology.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • Targeted therapy with tyrosine kinase inhibitors (TKIs) is standard for advanced non-small cell lung cancer (NSCLC) with specific epidermal growth factor receptor (EGFR) mutations.
  • Identifying resistance mechanisms, including the p.T790M mutation, is essential for guiding subsequent treatment lines.
  • Molecular testing alone may not identify all resistance mechanisms, necessitating complementary diagnostic approaches.

Purpose of the Study:

  • To review the significance of morphological changes in NSCLC acquired resistance to TKIs.
  • To emphasize the role of cytopathology in identifying resistance mechanisms.
  • To discuss the transition of adenocarcinoma to other NSCLC subtypes (squamous cell carcinoma, small cell lung cancer, large-cell neuroendocrine carcinoma) upon TKI resistance.

Main Methods:

  • Comprehensive literature review of studies on TKI resistance in NSCLC.
  • Analysis of morphological alterations observed in cytopathological samples.
  • Correlation of morphological changes with molecular resistance mechanisms.

Main Results:

  • Acquired resistance to TKIs in NSCLC can manifest as significant morphological changes.
  • These morphological changes can include transformation into squamous cell carcinoma, small cell lung cancer, or large-cell neuroendocrine carcinoma.
  • Cytopathology can provide crucial diagnostic clues when molecular testing is inconclusive.

Conclusions:

  • Morphological assessment via cytopathology is vital for diagnosing TKI resistance in NSCLC.
  • Recognizing these phenotypic transitions is critical for appropriate patient management and treatment selection.
  • Integrated diagnostic strategies combining molecular and morphological analyses improve outcomes for NSCLC patients.
Keywords:
Lung cancerMolecular pathologyMorphological transitionNon-small cell lung cancerTyrosine kinase inhibitors

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