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Comprehensive Tissue Genomic Profiling Reveals ALK-EML4 Fusionand TP53 Splice-Site Mutation in Metastatic Lung Adenocarcinoma

Clinical History & Chronological Summary

  • Presentation: 31-year-old female with symptoms suggestive of right upper lobe lung involvement; PET-CT showed a RUL mass with lymphadenopathy and suspicious breast parenchymal uptake, raising concern for metastasis.
  • Diagnosis: Biopsy of the right supraclavicular lymph node confirmed metastatic poorly differentiated carcinoma consistent with a
    lung primary; IHC showed TTF-1 and Napsin A positivity, supporting lung adenocarcinoma.
  • Further evaluation: Comprehensive tissue-based NGS profiling (OncoIndx, OneCell Diagnostics) was performed on FFPE tissue
    from the right supraclavicular lymph node to identify actionable molecular alterations and inform targeted therapy selection.

 

Clinical Challenges

  • Metastatic disease with nodal and possible distant involvement limited surgical options, necessitating systemic therapy.
  • Multiple candidate mutations required precision profiling to define dominant oncogenic drivers and guide selection between targeted and immune-based therapies.
  • PD-L1 expression (TPS 50%) indicated checkpoint inhibitor sensitivity, but concurrent ALK-EML4 fusion prioritized targeted ALK inhibition as per guidelines.
  • Need for longitudinal monitoring using liquid biopsy to detect resistance evolution.

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